Invertase （INV） hydrolyzes sucrose into glucose and fructose, thereby playing key roles in primary metabolism and plant development. Based on their pH optima and sub-cellular locations, INVs are categorized into cel...Invertase （INV） hydrolyzes sucrose into glucose and fructose, thereby playing key roles in primary metabolism and plant development. Based on their pH optima and sub-cellular locations, INVs are categorized into cell wall, cytoplasmic, and vacuolar subgroups, abbreviated as CWlN, CIN, and VlN, respectively. The broad importance and implications of INVs in plant development and crop productivity have attracted enormous interest to examine INV function and regulation from multiple perspectives. Here, we review some exciting advances in this area over the last two decades, focusing on （1） new or emerging roles of INV in plant development and regulation at the post-translational level through interaction with inhibitors, （2） cross-talk between INV-mediated sugar signaling and hormonal control of development, and （3） sugar- and INV-mediated responses to drought and heat stresses and their impact on seed and fruit set. Finally, we discuss major questions arising from this new progress and outline future directions for unraveling mechanisms underlying INV-mediated plant development and their potential applications in plant biotechnology and agriculture.展开更多
AIM To report a single Australian oncology unit′s experience with the management of patients with hepatocellular carcinoma (HCC), in the context of a literature review of the current management issues. METHODS Retros...AIM To report a single Australian oncology unit′s experience with the management of patients with hepatocellular carcinoma (HCC), in the context of a literature review of the current management issues. METHODS Retrospective case record review of 76 patients with diagnosis of HCC referred to the unit between 1984 and 1995. RESULTS Sixty three patients had adequate records for analysis. Thirty six (56%) were migrants with half from Southeast Asia. Twenty four patients had a documented viral aetiology. Nine (14%) of 51 patients with pathological confirmation of HCC had normal alpha fetoprotein levels. Median survival of the 20 patients managed palliatively was 5 weeks compared to 16 weeks for the cohort overall. Surgery in 16 patients rendered all initially disease free with a median survival of 88 weeks. Chemoembolisation induced tumor responses in 5 of the 11 patients so treated. Systemic chemotherapy and tamoxifen treatment caused tumor response in two of 12 and one of 25 respectively. CONCLUSION Prolonged survival of patients with HCC depends on early detection of small tumors suitable for surgical resection. Other active treatments are palliative in intent and have limited success. In addition to tumor response and survival duration, the toxicities of therapies and the overall quality of life of patients need to be considered as important outcomes. Viral hepatitis prevention and screening of individuals at risk are strategies that are important for HCC management in communities where the disease is endemic.展开更多
Purpose: The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the fea...Purpose: The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the assessment.Methods: An expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. Criterion-referenced skill performance and completion time were the recommended forms of evaluation. Children, 8–12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert(n = 19, 21% female) review process. Convergent validity was evaluated by age and gender associations with assessment performance. Inter-and intra-rater(n = 53, 34% female) objectivity and test–retest(n = 60, 47% female) reliability were assessed through repeated test administration.Results: Median total score was 21 of 28 points(range 5–28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments(95% confidence interval(CI) of difference:-0.7 to 0.6;p = 0.91) or with/without footwear(95%CI of difference:-2.5 to 1.9; p = 0.77). Older age(p < 0.001, η2= 0.15) and male gender(p < 0.001, η2= 0.02)were associated with a higher total score. Inter-rater objectivity evidence was excellent(intraclass correlation coefficient(ICC) = 0.99) for completion time and substantial for skill score(ICC = 0.69) for 104 attempts by 53 children(34% female). Intra-rater objectivity was moderate(ICC = 0.52) for skill score and excellent for completion time(ICC = 0.99). Reliability was excellent for completion time over a short(2–4 days; ICC = 0.84) or long(8–14days; ICC = 0.82) interval. Skill score reliability was moderate(ICC = 0.46) over a short interval, a展开更多
Human-emitted greenhouse gases(GHGs)have resulted in a long-term and unequivocal warming of the planet(IPCC,2019).More than 90%of the excess heat is stored within the world's oceans,where it accumulates and causes...Human-emitted greenhouse gases(GHGs)have resulted in a long-term and unequivocal warming of the planet(IPCC,2019).More than 90%of the excess heat is stored within the world's oceans,where it accumulates and causes increases in ocean temperature(Rhein et al.,2013;Abram et al.,2019).展开更多
The global physical and biogeochemical environment has been substantially altered in response to increased atmospheric greenhouse gases from human activities.In 2023,the sea surface temperature(SST)and upper 2000 m oc...The global physical and biogeochemical environment has been substantially altered in response to increased atmospheric greenhouse gases from human activities.In 2023,the sea surface temperature(SST)and upper 2000 m ocean heat content(OHC)reached record highs.The 0–2000 m OHC in 2023 exceeded that of 2022 by 15±10 ZJ(1 Zetta Joules=1021 Joules)(updated IAP/CAS data);9±5 ZJ(NCEI/NOAA data).The Tropical Atlantic Ocean,the Mediterranean Sea,and southern oceans recorded their highest OHC observed since the 1950s.Associated with the onset of a strong El Niño,the global SST reached its record high in 2023 with an annual mean of~0.23℃ higher than 2022 and an astounding>0.3℃ above 2022 values for the second half of 2023.The density stratification and spatial temperature inhomogeneity indexes reached their highest values in 2023.展开更多
Changes in ocean heat content(OHC), salinity, and stratification provide critical indicators for changes in Earth’s energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse...Changes in ocean heat content(OHC), salinity, and stratification provide critical indicators for changes in Earth’s energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth’s climate system. In 2022, the world’s oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum.According to IAP/CAS data, the 0–2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ(1 Zetta Joules = 1021Joules);and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins(the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the “salty gets saltier–fresh gets fresher” pattern, also reached its highest level on record in 2022,implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Ni?a event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.展开更多
The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content(OHC). Here, we provide the first analysis of recent OHC cha...The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content(OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year’s record value by 14 ± 11 ZJ(1 zetta J = 1021 J) using the IAP/CAS dataset and by16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Nino-Southern Oscillation(ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans,and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.展开更多
Background:Parkinson’s disease(PD)is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies(LB).During the course of disease,misfoldedα-synu...Background:Parkinson’s disease(PD)is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies(LB).During the course of disease,misfoldedα-synuclein,the major constituent of LB,spreads to different regions of the brain in a prion-like fashion,giving rise to successive non-motor and motor symptoms.Etiology is likely multifactorial,and involves interplay among aging,genetic susceptibility and environmental factors.Main body:The prevalence of PD rises exponentially with age,and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death.However,the majority of those over the age of 80 do not have PD,thus other factors in addition to aging are needed to cause disease.Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk.Nevertheless,the causality of most environmental factors is not conclusively established,and alternative explanations such as reverse causality and recall bias cannot be excluded.The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD.Rare mutations as well as common variants in genes such as SNCA,LRRK2 and GBA are associated with risk of PD,but Mendelian causes collectively only account for 5%of PD and common polymorphisms are associated with small increase in PD risk.Heritability of PD has been estimated to be around 30%.Thus,aging,genetics and environmental factors each alone is rarely sufficient to cause PD for most patients.Conclusion:PD is a multifactorial disorder involving interplay of aging,genetics and environmental factors.This has implications on the development of appropriate animal models of PD which take all these factors into account.Common converging pathways likely include mitochondrial dysfunction,impaired autophagy,oxidative stress and neuroinflammation,which are associated with the accumulation and spread 展开更多
In this editorial we comment on the article published in a recent issue of the World Journal of Clinical Cases.This article described a novel ultrasound-guided lateral recess block approach in treating a patient with ...In this editorial we comment on the article published in a recent issue of the World Journal of Clinical Cases.This article described a novel ultrasound-guided lateral recess block approach in treating a patient with lateral recess stenosis.The impact of spinal pain-related disability extends significantly,causing substantial human suffering and medical costs.Each county has its preferred treatment strategies for spinal pain.Here,we explore the lower back pain(LBP)treatment algorithm recommended in France.The treatment algorithm for LBP recommended by the French National Authority for Health emphasizes early patient activity and minimal medication use.It encourages the continuation of daily activities,limits excessive medication and spinal injections,and incorporates psychological assessments and non-pharmacological therapies for chronic cases.However,the algorithm may not aggressively address acute pain in the early stages,potentially delaying relief and increasing the risk of chronicity.Additionally,the recommended infiltrations primarily involve caudal epidural steroid injections,with limited consideration for other injection procedures,such as transforaminal or interlaminar epidural steroid injections.The fixed follow-up timeline may not accommodate patients who do not respond to initial treatment or experience intense pain,potentially delaying the exploration of alternative therapies.Despite these limitations,understanding the strengths and weaknesses of the French approach could inform adaptations in LBP treatment strategies globally,potentially enhancing patient outcomes and satisfaction across diverse healthcare systems.展开更多
Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is lacking.We investigated the risk and protective factors related to SIDS.Methods We con...Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is lacking.We investigated the risk and protective factors related to SIDS.Methods We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors.PubMed/MEDLINE,Embase,EBSCO,and Google Scholar were searched from inception until January 18,2023.Data extraction,quality assessment,and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines.According to observational evidence,credibility was graded and classified by class and quality of evidence(CE;convincing,highly suggestive,suggestive,weak,or not significant).Our study protocol was registered with PROSPERO(CRD42023458696).The risk and protective factors related to SIDS are presented as equivalent odds ratios(eORs).Results We identified eight original meta-analyses,including 152 original articles,covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents.Several risk factors,including prenatal drug exposure[eOR=7.84(95%CI=4.81–12.79),CE=highly suggestive],prenatal opioid exposure[9.55(95%CI=4.87–18.72),CE=suggestive],prenatal methadone exposure[9.52(95%CI=3.34–27.10),CE=weak],prenatal cocaine exposure[4.38(95%CI=1.95–9.86),CE=weak],prenatal maternal smoking[2.25(95%CI=1.95–2.60),CE=highly suggestive],postnatal maternal smoking[1.97(95%CI=1.75–2.22),CE=weak],bed sharing[2.89(95%CI=1.81–4.60),CE=weak],and infants found with heads covered by bedclothes after last sleep[11.01(95%CI=5.40–22.45),CE=suggestive],were identified.On the other hand,three protective factors,namely,breastfeeding[0.57(95%CI=0.39–0.83),CE=non-significant],supine sleeping position[0.48(95%CI=0.37–0.63),CE=suggestive],and pacifier use[0.44(95%CI=0.30–0.65),CE=weak],were also identified.Conclusions Based on the evidence,we propose several risk and protective factors for SIDS.This s展开更多
In Quebec,Canada,the public healthcare system offers free medical services.However,patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage.In contras...In Quebec,Canada,the public healthcare system offers free medical services.However,patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage.In contrast,private clinics provide expedited care but are relatively scarce and entail out-of-pocket expenses.Once a patient with pain caused by a spinal disorder meets a pain medicine specialist,spinal intervention is quickly performed when indicated,and patients are provided lifestyle advice.Transforaminal epidural steroid injections are frequently administered to patients with radicular pain,and steroid injections are administered on a facet joint to control low back or neck pain.Additionally,medial branch blocks are performed prior to thermocoagulation.France’s universal healthcare system ensures accessibility at controlled costs.It emphasizes physical activity and provides free physical therapy services.However,certain interventions,such as transforaminal and interlaminar epidural injections,are not routinely used in France owing to limited therapeutic efficacy and safety concerns.This underutilization may be a potential cause of chronic pain for many patients.By examining the differences,strengths,and weaknesses of these two systems,valuable insights can be gained for the enhancement of global spinal pain management strategies,ultimately leading to improved patient outcomes and satisfaction.展开更多
AIM To prospectively evaluate the performance of Dopplerultrasonography(US) for the detection of transjugular intrahepatic portosystemic shunt(TIPS) dysfunction within a multicenter cohort of cirrhotic patients.METHOD...AIM To prospectively evaluate the performance of Dopplerultrasonography(US) for the detection of transjugular intrahepatic portosystemic shunt(TIPS) dysfunction within a multicenter cohort of cirrhotic patients.METHODS This study was conducted in 10 french teaching hospitals. After TIPS insertion, angiography and liver Doppler-US were carried out every six months to detect dysfunction(defined by a portosystemic gradient ≥ 12 mm Hg and/or a stent stenosis ≥ 50%). The association between ultrasonographic signs and dysfunction was studied by logistic random-effects models, and the diagnostic performance of each Doppler criterion was estimated by the bootstrap method. This study was approved by the ethics committee of Tours.RESULTS Two hundred and eighteen pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables significantly associated with dysfunction were: The speed of flow in the portal vein(P = 0.008), the reversal of flow in the right(P = 0.038) and left(P = 0.049) portal branch, the loss of modulation of portal flow by the right atrium(P = 0.0005), ascites(P = 0.001) and the overall impression of the operator(P = 0.0001). The diagnostic performances of these variables were low; sensitivity was < 58% and negative predictive value was < 73%. Therefore, dysfunction cannot be ruled out from Doppler-US. CONCLUSION The performance of Doppler-US for the detection of TIPS dysfunction is poor compared to angiography. New tools are needed to improve diagnosis of TIPS dysfunction.展开更多
In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ varia...In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ variable region and Cμand Cδheavy chain constant exons.1 After encountering antigen,B cells undergo class switch recombination(CSR)by which the Cμgene is substituted with Cγ,Cεor Cα,thereby generating IgG,IgE and IgA antibodies of the same antigenic specificity but with new effector functions.CSR requires the DNA-editing enzyme activation-induced deaminase(AID).展开更多
Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal ...Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. Methods: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 ±26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. Results: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81%and 62%; TIPS, 88%and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. Conclusions: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.展开更多
The goal of this project was to design, build, and test a pilot-scale floating modular treatment system for total phosphorus （TP） removal from nutrient-impaired lakes in central Florida, USA. The treatment sys-tem c...The goal of this project was to design, build, and test a pilot-scale floating modular treatment system for total phosphorus （TP） removal from nutrient-impaired lakes in central Florida, USA. The treatment sys-tem consisted of biological and physical-chemical treatment modules. First, investigations of prospective biological and physical-chemical treatment processes in mesocosms and in bench-scale experiments were conducted. Thirteen different mesocosms were constructed with a variety of substrates and combi-nations of macrophytes and tested for TP and orthophosphate （PO4-^3） removal efficiencies and potential areal removal rates. Bench-scale jar tests and column tests of seven types of absorptive media in addition to three commercial resins were conducted in order to test absorptive capacity. Once isolated process testing was complete, a floating island treatment system （FITS） was designed and deployed for eight months in a lake in central Florida. Phosphorus removal efficiencies of the mesocosm systems averaged about 40%-50%, providing an average uptake of 5.0 g.m ^2.a ^1 across all mesocosms. The best-performing mesocosms were a submerged aquatic vegetation （SAV） mesocosm and an algae scrubber （AGS）, which removed 20 and 50 mg.m ^2.d ^1, respectively, for an average removal of 5.5 and 12.0 g.m ^2.a ^1 for the SAV and AGS systems, Of the absorptive media, the best performance was alum residual （AR）, which reduced PO4-^3 concentrations by about 75% after 5 min of contact time. Of the commercial resins tested, the PhosX resin was superior to the others, removing about 40% of phosphorus after 30 rain and 60% after 60min. Under baseline operation conditions during deployment, the FITS exhibited mean PO4-^3 removal efficiencies of 53%; using the 50th and 90th percentile of PO4-^3 removal during deployment, and the footprint of the FITS system, yielded efficiencies for the combined FITS system of 56% and 86%, respectively, and areal phosphorus removal rates between 8.9 and 16.5 g.m ^2.a ^1展开更多
The long-term warming of the ocean is a critical indicator of both the past and present state of the climate system. It also provides insights about the changes to come, owing to the persistence of both decadal variat...The long-term warming of the ocean is a critical indicator of both the past and present state of the climate system. It also provides insights about the changes to come, owing to the persistence of both decadal variations and secular trends,which the ocean records extremely well(Hansen et al., 2011;IPCC, 2013;Rhein et al., 2013;Trenberth et al., 2016;Abram et al., 2019).展开更多
Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP),...Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.展开更多
文摘Invertase （INV） hydrolyzes sucrose into glucose and fructose, thereby playing key roles in primary metabolism and plant development. Based on their pH optima and sub-cellular locations, INVs are categorized into cell wall, cytoplasmic, and vacuolar subgroups, abbreviated as CWlN, CIN, and VlN, respectively. The broad importance and implications of INVs in plant development and crop productivity have attracted enormous interest to examine INV function and regulation from multiple perspectives. Here, we review some exciting advances in this area over the last two decades, focusing on （1） new or emerging roles of INV in plant development and regulation at the post-translational level through interaction with inhibitors, （2） cross-talk between INV-mediated sugar signaling and hormonal control of development, and （3） sugar- and INV-mediated responses to drought and heat stresses and their impact on seed and fruit set. Finally, we discuss major questions arising from this new progress and outline future directions for unraveling mechanisms underlying INV-mediated plant development and their potential applications in plant biotechnology and agriculture.
文摘AIM To report a single Australian oncology unit′s experience with the management of patients with hepatocellular carcinoma (HCC), in the context of a literature review of the current management issues. METHODS Retrospective case record review of 76 patients with diagnosis of HCC referred to the unit between 1984 and 1995. RESULTS Sixty three patients had adequate records for analysis. Thirty six (56%) were migrants with half from Southeast Asia. Twenty four patients had a documented viral aetiology. Nine (14%) of 51 patients with pathological confirmation of HCC had normal alpha fetoprotein levels. Median survival of the 20 patients managed palliatively was 5 weeks compared to 16 weeks for the cohort overall. Surgery in 16 patients rendered all initially disease free with a median survival of 88 weeks. Chemoembolisation induced tumor responses in 5 of the 11 patients so treated. Systemic chemotherapy and tamoxifen treatment caused tumor response in two of 12 and one of 25 respectively. CONCLUSION Prolonged survival of patients with HCC depends on early detection of small tumors suitable for surgical resection. Other active treatments are palliative in intent and have limited success. In addition to tumor response and survival duration, the toxicities of therapies and the overall quality of life of patients need to be considered as important outcomes. Viral hepatitis prevention and screening of individuals at risk are strategies that are important for HCC management in communities where the disease is endemic.
基金funded by a grant from the Canadian Institutes of Health Research awarded to Dr. Meghann Lloyd and Dr. Mark Tremblay (IHD 94356)
文摘Purpose: The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the assessment.Methods: An expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. Criterion-referenced skill performance and completion time were the recommended forms of evaluation. Children, 8–12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert(n = 19, 21% female) review process. Convergent validity was evaluated by age and gender associations with assessment performance. Inter-and intra-rater(n = 53, 34% female) objectivity and test–retest(n = 60, 47% female) reliability were assessed through repeated test administration.Results: Median total score was 21 of 28 points(range 5–28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments(95% confidence interval(CI) of difference:-0.7 to 0.6;p = 0.91) or with/without footwear(95%CI of difference:-2.5 to 1.9; p = 0.77). Older age(p < 0.001, η2= 0.15) and male gender(p < 0.001, η2= 0.02)were associated with a higher total score. Inter-rater objectivity evidence was excellent(intraclass correlation coefficient(ICC) = 0.99) for completion time and substantial for skill score(ICC = 0.69) for 104 attempts by 53 children(34% female). Intra-rater objectivity was moderate(ICC = 0.52) for skill score and excellent for completion time(ICC = 0.99). Reliability was excellent for completion time over a short(2–4 days; ICC = 0.84) or long(8–14days; ICC = 0.82) interval. Skill score reliability was moderate(ICC = 0.46) over a short interval, a
基金supported by the National Key Research and Development Program of China (Grant Nos. 2016YFC1401806 and 2017YFA0603202)sponsored by the US National Science Foundation+2 种基金funded in partnership with the NOAA OAR Ocean Observing and Monitoring Divisionpartially supported by the Regional and Global Model Analysis (RGMA) component of the Earth and Environmental System Modeling Program of the U.S. Department of Energy’s Office of Biological & Environmental Research (BER) via National Science Foundation IA 1844590supported in part by NSF Award #AGS-1419571
文摘Human-emitted greenhouse gases(GHGs)have resulted in a long-term and unequivocal warming of the planet(IPCC,2019).More than 90%of the excess heat is stored within the world's oceans,where it accumulates and causes increases in ocean temperature(Rhein et al.,2013;Abram et al.,2019).
基金supported by the National Natural Science Foundation of China (Grant Nos. 42076202, 42122046, 42206208 and 42261134536)the Open Research Cruise NORC2022-10+NORC2022-303 supported by NSFC shiptime Sharing Projects 42149910+7 种基金the new Cornerstone Science Foundation through the XPLORER PRIZE, DAMO Academy Young Fellow, Youth Innovation Promotion Association, Chinese Academy of SciencesNational Key Scientific and Technological Infrastructure project “Earth System Science Numerical Simulator Facility” (EarthLab)sponsored by the US National Science Foundationsupported by NASA Awards 80NSSC17K0565, 80NSSC21K1191, and 80NSSC22K0046by the Regional and Global Model Analysis (RGMA) component of the Earth and Environmental System Modeling Program of the U.S. Department of Energy’s Office of Biological & Environmental Research (BER) via National Science Foundation IA 1947282supported by NOAA (Grant No. NA19NES4320002 to CISESS-MD at the University of Maryland)supported by the Young Talent Support Project of Guangzhou Association for Science and Technologyfunded by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) in agreement between INGV, ENEA, and GNV SpA shipping company that provides hospitality on its commercial vessels
文摘The global physical and biogeochemical environment has been substantially altered in response to increased atmospheric greenhouse gases from human activities.In 2023,the sea surface temperature(SST)and upper 2000 m ocean heat content(OHC)reached record highs.The 0–2000 m OHC in 2023 exceeded that of 2022 by 15±10 ZJ(1 Zetta Joules=1021 Joules)(updated IAP/CAS data);9±5 ZJ(NCEI/NOAA data).The Tropical Atlantic Ocean,the Mediterranean Sea,and southern oceans recorded their highest OHC observed since the 1950s.Associated with the onset of a strong El Niño,the global SST reached its record high in 2023 with an annual mean of~0.23℃ higher than 2022 and an astounding>0.3℃ above 2022 values for the second half of 2023.The density stratification and spatial temperature inhomogeneity indexes reached their highest values in 2023.
基金supported by the National Natural Science Foundation of China (Grant Nos. 42122046 and 42076202)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB42040402)+4 种基金sponsored by the US National Science Foundationsupported by NASA Awards 80NSSC17K0565 and 80NSSC22K0046by the Regional and Global Model Analysis (RGMA) component of the Earth and Environmental System Modeling Program of the U.S. Department of Energy’s Office of Biological & Environmental Research (BER) via National Science Foundation IA 1947282supported by NOAA (Grant No. NA19NES4320002 to CISESS-MD at the University of Maryland)supported by the Young Talent Support Project of Guangzhou Association for Science and Technology。
文摘Changes in ocean heat content(OHC), salinity, and stratification provide critical indicators for changes in Earth’s energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth’s climate system. In 2022, the world’s oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum.According to IAP/CAS data, the 0–2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ(1 Zetta Joules = 1021Joules);and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins(the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the “salty gets saltier–fresh gets fresher” pattern, also reached its highest level on record in 2022,implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Ni?a event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.
基金supported by the National Natural Science Foundation of China(Grant No.42122046,42076202)Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB42040402)+5 种基金National Natural Science Foundation of China(Grant No.42076202)National Key R&D Program of China(Grant No.2017YFA0603202)Key Deployment Project of Centre for Ocean Mega-Research of Science,CAS(Grant Nos.COMS2019Q01 and COMS2019Q07)NCAR is sponsored by the US National Science Foundationsupported by NASA Award 80NSSC17K0565the Regional and Global Model Analysis(RGMA)component of the Earth and Environmental System Modeling Program of the U.S.Department of Energy’s Office of Biological&Environmental Research(BER)via National Science Foundation IA 1844590。
文摘The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content(OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year’s record value by 14 ± 11 ZJ(1 zetta J = 1021 J) using the IAP/CAS dataset and by16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Nino-Southern Oscillation(ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans,and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.
基金Tai Hung Fai Charitable Foundation-Edwin S H Leong Research Programmefor Parkinson's DiseaseThe Henry G.Leong Endowed Professorship in Neurology+1 种基金The Donation Fund for Neurology ResearchHealth and MedicalResearch Fund(HMRF),Food and Health Bureau,Hong Kong SA.R.
文摘Background:Parkinson’s disease(PD)is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies(LB).During the course of disease,misfoldedα-synuclein,the major constituent of LB,spreads to different regions of the brain in a prion-like fashion,giving rise to successive non-motor and motor symptoms.Etiology is likely multifactorial,and involves interplay among aging,genetic susceptibility and environmental factors.Main body:The prevalence of PD rises exponentially with age,and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death.However,the majority of those over the age of 80 do not have PD,thus other factors in addition to aging are needed to cause disease.Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk.Nevertheless,the causality of most environmental factors is not conclusively established,and alternative explanations such as reverse causality and recall bias cannot be excluded.The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD.Rare mutations as well as common variants in genes such as SNCA,LRRK2 and GBA are associated with risk of PD,but Mendelian causes collectively only account for 5%of PD and common polymorphisms are associated with small increase in PD risk.Heritability of PD has been estimated to be around 30%.Thus,aging,genetics and environmental factors each alone is rarely sufficient to cause PD for most patients.Conclusion:PD is a multifactorial disorder involving interplay of aging,genetics and environmental factors.This has implications on the development of appropriate animal models of PD which take all these factors into account.Common converging pathways likely include mitochondrial dysfunction,impaired autophagy,oxidative stress and neuroinflammation,which are associated with the accumulation and spread
基金Supported by The National Research Foundation of Korea Grant funded by the Korea Government,No.00219725.
文摘In this editorial we comment on the article published in a recent issue of the World Journal of Clinical Cases.This article described a novel ultrasound-guided lateral recess block approach in treating a patient with lateral recess stenosis.The impact of spinal pain-related disability extends significantly,causing substantial human suffering and medical costs.Each county has its preferred treatment strategies for spinal pain.Here,we explore the lower back pain(LBP)treatment algorithm recommended in France.The treatment algorithm for LBP recommended by the French National Authority for Health emphasizes early patient activity and minimal medication use.It encourages the continuation of daily activities,limits excessive medication and spinal injections,and incorporates psychological assessments and non-pharmacological therapies for chronic cases.However,the algorithm may not aggressively address acute pain in the early stages,potentially delaying relief and increasing the risk of chronicity.Additionally,the recommended infiltrations primarily involve caudal epidural steroid injections,with limited consideration for other injection procedures,such as transforaminal or interlaminar epidural steroid injections.The fixed follow-up timeline may not accommodate patients who do not respond to initial treatment or experience intense pain,potentially delaying the exploration of alternative therapies.Despite these limitations,understanding the strengths and weaknesses of the French approach could inform adaptations in LBP treatment strategies globally,potentially enhancing patient outcomes and satisfaction across diverse healthcare systems.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT,RS-2023-00248157)。
文摘Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is lacking.We investigated the risk and protective factors related to SIDS.Methods We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors.PubMed/MEDLINE,Embase,EBSCO,and Google Scholar were searched from inception until January 18,2023.Data extraction,quality assessment,and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines.According to observational evidence,credibility was graded and classified by class and quality of evidence(CE;convincing,highly suggestive,suggestive,weak,or not significant).Our study protocol was registered with PROSPERO(CRD42023458696).The risk and protective factors related to SIDS are presented as equivalent odds ratios(eORs).Results We identified eight original meta-analyses,including 152 original articles,covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents.Several risk factors,including prenatal drug exposure[eOR=7.84(95%CI=4.81–12.79),CE=highly suggestive],prenatal opioid exposure[9.55(95%CI=4.87–18.72),CE=suggestive],prenatal methadone exposure[9.52(95%CI=3.34–27.10),CE=weak],prenatal cocaine exposure[4.38(95%CI=1.95–9.86),CE=weak],prenatal maternal smoking[2.25(95%CI=1.95–2.60),CE=highly suggestive],postnatal maternal smoking[1.97(95%CI=1.75–2.22),CE=weak],bed sharing[2.89(95%CI=1.81–4.60),CE=weak],and infants found with heads covered by bedclothes after last sleep[11.01(95%CI=5.40–22.45),CE=suggestive],were identified.On the other hand,three protective factors,namely,breastfeeding[0.57(95%CI=0.39–0.83),CE=non-significant],supine sleeping position[0.48(95%CI=0.37–0.63),CE=suggestive],and pacifier use[0.44(95%CI=0.30–0.65),CE=weak],were also identified.Conclusions Based on the evidence,we propose several risk and protective factors for SIDS.This s
基金Supported by National Research Foundation of Korea Grant,No.00219725.
文摘In Quebec,Canada,the public healthcare system offers free medical services.However,patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage.In contrast,private clinics provide expedited care but are relatively scarce and entail out-of-pocket expenses.Once a patient with pain caused by a spinal disorder meets a pain medicine specialist,spinal intervention is quickly performed when indicated,and patients are provided lifestyle advice.Transforaminal epidural steroid injections are frequently administered to patients with radicular pain,and steroid injections are administered on a facet joint to control low back or neck pain.Additionally,medial branch blocks are performed prior to thermocoagulation.France’s universal healthcare system ensures accessibility at controlled costs.It emphasizes physical activity and provides free physical therapy services.However,certain interventions,such as transforaminal and interlaminar epidural injections,are not routinely used in France owing to limited therapeutic efficacy and safety concerns.This underutilization may be a potential cause of chronic pain for many patients.By examining the differences,strengths,and weaknesses of these two systems,valuable insights can be gained for the enhancement of global spinal pain management strategies,ultimately leading to improved patient outcomes and satisfaction.
基金Supported by Innovative techniques support of French Ministry of Health STIC 07the Societe Nationale Francaise de Gastroenterologie
文摘AIM To prospectively evaluate the performance of Dopplerultrasonography(US) for the detection of transjugular intrahepatic portosystemic shunt(TIPS) dysfunction within a multicenter cohort of cirrhotic patients.METHODS This study was conducted in 10 french teaching hospitals. After TIPS insertion, angiography and liver Doppler-US were carried out every six months to detect dysfunction(defined by a portosystemic gradient ≥ 12 mm Hg and/or a stent stenosis ≥ 50%). The association between ultrasonographic signs and dysfunction was studied by logistic random-effects models, and the diagnostic performance of each Doppler criterion was estimated by the bootstrap method. This study was approved by the ethics committee of Tours.RESULTS Two hundred and eighteen pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables significantly associated with dysfunction were: The speed of flow in the portal vein(P = 0.008), the reversal of flow in the right(P = 0.038) and left(P = 0.049) portal branch, the loss of modulation of portal flow by the right atrium(P = 0.0005), ascites(P = 0.001) and the overall impression of the operator(P = 0.0001). The diagnostic performances of these variables were low; sensitivity was < 58% and negative predictive value was < 73%. Therefore, dysfunction cannot be ruled out from Doppler-US. CONCLUSION The performance of Doppler-US for the detection of TIPS dysfunction is poor compared to angiography. New tools are needed to improve diagnosis of TIPS dysfunction.
基金This work was financially supported through a grant from the ANR(project EpiSwitch-3'RR 2016).NG was supported through a grant from the Association de Specialisation et dOrientation Scientifique(Lebanon)and the municipality of Khiam(Lebanon).HI was supported through a grant from CORC(FA/NP 2015-109)and the University of Limoges.The authors thank the GenoLim platfom and the Cytometry platfom of the University of Limoges for sequencing and cell sorting FB was supported through a grant from the Fondation Partenariale de IUniversite de Limoges and ALURAD.
文摘In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ variable region and Cμand Cδheavy chain constant exons.1 After encountering antigen,B cells undergo class switch recombination(CSR)by which the Cμgene is substituted with Cγ,Cεor Cα,thereby generating IgG,IgE and IgA antibodies of the same antigenic specificity but with new effector functions.CSR requires the DNA-editing enzyme activation-induced deaminase(AID).
文摘Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. Methods: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 ±26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. Results: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81%and 62%; TIPS, 88%and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. Conclusions: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.
基金the Lake Jesup Total Phosphorus Removal Treatment Technologies Floating Island Pilot Project (25104) of St. Johns River Water Management District Palatka+1 种基金 FL USA
文摘The goal of this project was to design, build, and test a pilot-scale floating modular treatment system for total phosphorus （TP） removal from nutrient-impaired lakes in central Florida, USA. The treatment sys-tem consisted of biological and physical-chemical treatment modules. First, investigations of prospective biological and physical-chemical treatment processes in mesocosms and in bench-scale experiments were conducted. Thirteen different mesocosms were constructed with a variety of substrates and combi-nations of macrophytes and tested for TP and orthophosphate （PO4-^3） removal efficiencies and potential areal removal rates. Bench-scale jar tests and column tests of seven types of absorptive media in addition to three commercial resins were conducted in order to test absorptive capacity. Once isolated process testing was complete, a floating island treatment system （FITS） was designed and deployed for eight months in a lake in central Florida. Phosphorus removal efficiencies of the mesocosm systems averaged about 40%-50%, providing an average uptake of 5.0 g.m ^2.a ^1 across all mesocosms. The best-performing mesocosms were a submerged aquatic vegetation （SAV） mesocosm and an algae scrubber （AGS）, which removed 20 and 50 mg.m ^2.d ^1, respectively, for an average removal of 5.5 and 12.0 g.m ^2.a ^1 for the SAV and AGS systems, Of the absorptive media, the best performance was alum residual （AR）, which reduced PO4-^3 concentrations by about 75% after 5 min of contact time. Of the commercial resins tested, the PhosX resin was superior to the others, removing about 40% of phosphorus after 30 rain and 60% after 60min. Under baseline operation conditions during deployment, the FITS exhibited mean PO4-^3 removal efficiencies of 53%; using the 50th and 90th percentile of PO4-^3 removal during deployment, and the footprint of the FITS system, yielded efficiencies for the combined FITS system of 56% and 86%, respectively, and areal phosphorus removal rates between 8.9 and 16.5 g.m ^2.a ^1
基金supported by the National Key R&D Program of China (Grant No. 2017YFA0603202)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB42040402)+4 种基金Key Deployment Project of Centre for Ocean Mega-Research of Science, CAS (Grant No. COMS2019Q01)sponsored by the US National Science Foundationsupported by NASA Award 80NSSC17K0565the Regional and Global Model Analysis (RGMA) component of the Earth and Environmental System Modeling Program of the U.S. Department of Energy's Office of Biological & Environmental Research (BER) via National Science Foundation IA 1844590partially supported by NOAA (grant NA14NES4320003 to CISESS-MD at the University of Maryland)。
文摘The long-term warming of the ocean is a critical indicator of both the past and present state of the climate system. It also provides insights about the changes to come, owing to the persistence of both decadal variations and secular trends,which the ocean records extremely well(Hansen et al., 2011;IPCC, 2013;Rhein et al., 2013;Trenberth et al., 2016;Abram et al., 2019).
基金Tai Hung Fai Charitable Foundation-Edwin S H Leong Research Programme for Parkinson’s DiseaseThe Henry G.Leong Endowed Professorship in NeurologyThe Donation Fund for Neurology Research.
文摘Mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA) represent two most common genetic causes of Parkinson’s disease (PD). Both genes are important in the autophagic-lysosomal pathway (ALP), defects of which are associated with α-synuclein (α-syn) accumulation. LRRK2 regulates macroautophagy via activation of the mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) and the calcium-dependent adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathways. Phosphorylation of Rab GTPases by LRRK2 regulates lysosomal homeostasis and endosomal trafficking. Mutant LRRK2 impairs chaperone-mediated autophagy, resulting in α-syn binding and oligomerization on lysosomal membranes. Mutations in GBA reduce glucocerebrosidase (GCase) activity, leading to glucosylceramide accumulation, α-syn aggregation and broad autophagic abnormalities. LRRK2 and GBA influence each other: GCase activity is reduced in LRRK2 mutant cells, and LRRK2 kinase inhibition can alter GCase activity in GBA mutant cells. Clinically, LRRK2 G2019S mutation seems to modify the effects of GBA mutation, resulting in milder symptoms than those resulting from GBA mutation alone. However, dual mutation carriers have an increased risk of PD and earlier age of onset compared with single mutation carriers, suggesting an additive deleterious effect on the initiation of PD pathogenic processes. Crosstalk between LRRK2 and GBA in PD exists, but its exact mechanism is unclear. Drugs that inhibit LRRK2 kinase or activate GCase are showing efficacy in pre-clinical models. Since LRRK2 kinase and GCase activities are also altered in idiopathic PD (iPD), it remains to be seen if these drugs will be useful in disease modification of iPD.
