In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research sch...In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.展开更多
In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhance...In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.展开更多
The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main c...The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main cause of the current global warming trend. The main inference from this stance is that the increase in temperature must occur after the release of greenhouse gases originating from the anthropic activities. However, no scientific evidence has been provided for this basic notion. Earth paleoclimatic records document the antecedence of temperature over CO<sub>2</sub> levels. For the past 65 Ma, the temperature parameter has controlled the subsequent increase in CO<sub>2</sub>. This includes the three rapid aberrant shifts and extreme climate transients at 55 Ma, 34 Ma, and 23 Ma REF _Ref159913672 \r \h \* MERGEFORMAT [1]. The simple fact of their existence points to the potential for highly nonlinear responses in climate forcing. Whatever these shifts and transients are, CO<sub>2</sub> remains a second order parameter in their evolution through time. Confronted with the past, a suitable response must therefore be given to the unresolved question of whether the CO<sub>2</sub> trends precede the temperature trends in the current period, or not. The assertion that the current global warming is anthropogenic in origin implicitly presupposes a change of paradigm, with the consequence (the increase in CO<sub>2</sub> levels) that occurred in Earth’s past being positioned as the cause of the warming for its present day climatic evolution. The compulsory assumption regarding the antecedence of CO<sub>2</sub> levels over the temperature trends is associated with the haziness of the methodological framework—i.e. the paradigm—and tightens the research fields on the likely origins of global warming. The possible involvement of an “aberrant” natural event, hidden behind the massive release of greenhouse gases, has not been considered by the MSC.展开更多
BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharma...BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharmacological factors are rare.This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition,leading to interstitial nephritis.The aim is to outline the case and its management,emphasizing the significance of recognizing uncommon causes of interstitial nephritis.CASE SUMMARY A 71-year-old female presented with stroke-like symptoms,including weakness,speech difficulties,and cognitive impairment.Chronic hypertension had been managed with hydrochlorothiazide(HCTZ)for over two decades.Upon admis-sion,severe hypokalemia and AKI were noted,prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis.Further investigations,including kidney biopsy,confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause.Despite treatment,initial renal function showed minimal improvement.However,with prednisolone therapy and supportive measures,her condition gradually improved,high-lighting the importance of comprehensive management.CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis.The occurrence of interstitial nephritis due to oxalate crystal deposition,especially without typical risk factors,emphasizes the need for vigilance in clinical practice.展开更多
BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trend...BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.展开更多
We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft ...We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid co...Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in 'one step', EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.展开更多
Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors ...Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.展开更多
An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless...An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless of their subspecialty interest,will encounter patients with DM during their career since this epidemic involves both developed and emerging countries.Diabetes results in complications affecting multiple organ systems,potentially resulting in adverse outcomes afterorthopaedic surgery.The purpose of this review is to discuss the pathophysiology of DM and its potential for impacting orthopaedic surgery patients.Diabetes adversely affects the outcome of all orthopaedic surgery subspecialties including foot and ankle,upper extremity,adult reconstructive,pediatrics,spine surgery and sports medicine.Poorly controlled diabetes negatively impacts bone,soft tissue,ligament and tendon healing.It is the complications of diabetes such as neuropathy,peripheral artery disease,and end stage renal disease which contributes to adverse outcomes.Well controlled diabetic patients without comorbidities have similar outcomes to patients without diabetes.Orthopaedic surgeons should utilize consultants who will assist in inpatient glycemic management as well as optimizing long term glycemic control.展开更多
A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timiz...A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timization problems and the increasing importance of low cost distributed parallel environments,it is a natural idea to replace a globar optimization by decentralized local sub-optimizations using GT which introduces the notion of games associated to an optimization problem.The GT/GAs combined optimization method is used for recon-struction and optimization problems by high lift multi-air-foil desing.Numerical results are favorably compared with single global GAs.The method shows teh promising robustness and efficient parallel properties of coupled GAs with different game scenarios for future advanced multi-disciplinary aerospace techmologies.展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
The long-term goal of the 2015 Paris Agreement is to limit global warming to well below 2 ℃above pre-industrial levels and to pursue efforts to limit it to 1.5 ℃. However, for climate mitigation and adaption efforts...The long-term goal of the 2015 Paris Agreement is to limit global warming to well below 2 ℃above pre-industrial levels and to pursue efforts to limit it to 1.5 ℃. However, for climate mitigation and adaption efforts, further studies are still needed to understand the regional consequences between the two global warming limits. Here we provide an assessment of changes in temperature extremes over China (relative to 1986-2005) at 1.5 ℃ and 2 ℃ warming levels (relative to 1861-1900) by using the 5th phase of the Coupled Model Intercomparison Project (CMIP5) models under three RCP scenarios (RCP2.6, RCP4.5, RCP8.5). Results show that the increases in mean temperature and temperature extremes over China are greater than that in global mean temperature. With respect to 1986-2005, the temperature of hottest day (TXx) and coldest night (TNn) are projected to increase about 1/1.6 ℃ and 1.1/1.8 ℃, whereas warm days (TX90p) and warm spell duration (WSDI) will increase about 7.5/13.8% and 15/30 d for the 1.5/2 ℃ global warming target, respectively. Under an additional 0.5 ℃ global warming, the projected increases of temperature in warmest day/night and coldest day/night are both more than 0.5 ℃ across almost the whole China. In Northwest China, Northeast China and the Tibetan Plateau, the projected changes are particularly sensitive to the additional 0.5 ℃ global warming, for example, multi-model mean increase in coldest day (TXn) and coldest night (TNn) will be about 2 times higher than a change of 0.5 ℃ global warming. Although the area-averaged changes in temperature extremes are very similar for different scenarios, spatial hotspot still exists, such as in Northwest China and North China, the increases in temperatures are apparently larger in RCP8.5 than that in RCP4.5.展开更多
文摘In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.
文摘In response to Dr.Yue et al's study on prognostic factors for post-hemihep-atectomy outcomes in hepatocellular carcinoma(HCC)patients,this critical review identifies methodological limitations and proposes enhancements for future research.While the study identifies liver stiffness measure and standard residual liver volume as potential predictors,concerns regarding small sample size,reliance on biochemical markers for safety assessment,and inadequate ad-justment for confounding variables are raised.Recommendations for rigorous methodology,including robust statistical analysis,consideration of confounding factors,and selection of outcome measures with clinical components,are proposed to strengthen prognostic assessments.Furthermore,validation of novel evaluation models is crucial for enhancing clinical applicability and advancing understanding of postoperative outcomes in patients with HCC undergoing hem-ihepatectomy.
文摘The “mainstream” climatology (MSC)—i.e. which includes the Intergovernmental Panel on Climate Change (IPCC) community—considers the present day massive release of greenhouse gases into the atmosphere as the main cause of the current global warming trend. The main inference from this stance is that the increase in temperature must occur after the release of greenhouse gases originating from the anthropic activities. However, no scientific evidence has been provided for this basic notion. Earth paleoclimatic records document the antecedence of temperature over CO<sub>2</sub> levels. For the past 65 Ma, the temperature parameter has controlled the subsequent increase in CO<sub>2</sub>. This includes the three rapid aberrant shifts and extreme climate transients at 55 Ma, 34 Ma, and 23 Ma REF _Ref159913672 \r \h \* MERGEFORMAT [1]. The simple fact of their existence points to the potential for highly nonlinear responses in climate forcing. Whatever these shifts and transients are, CO<sub>2</sub> remains a second order parameter in their evolution through time. Confronted with the past, a suitable response must therefore be given to the unresolved question of whether the CO<sub>2</sub> trends precede the temperature trends in the current period, or not. The assertion that the current global warming is anthropogenic in origin implicitly presupposes a change of paradigm, with the consequence (the increase in CO<sub>2</sub> levels) that occurred in Earth’s past being positioned as the cause of the warming for its present day climatic evolution. The compulsory assumption regarding the antecedence of CO<sub>2</sub> levels over the temperature trends is associated with the haziness of the methodological framework—i.e. the paradigm—and tightens the research fields on the likely origins of global warming. The possible involvement of an “aberrant” natural event, hidden behind the massive release of greenhouse gases, has not been considered by the MSC.
文摘BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharmacological factors are rare.This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition,leading to interstitial nephritis.The aim is to outline the case and its management,emphasizing the significance of recognizing uncommon causes of interstitial nephritis.CASE SUMMARY A 71-year-old female presented with stroke-like symptoms,including weakness,speech difficulties,and cognitive impairment.Chronic hypertension had been managed with hydrochlorothiazide(HCTZ)for over two decades.Upon admis-sion,severe hypokalemia and AKI were noted,prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis.Further investigations,including kidney biopsy,confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause.Despite treatment,initial renal function showed minimal improvement.However,with prednisolone therapy and supportive measures,her condition gradually improved,high-lighting the importance of comprehensive management.CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis.The occurrence of interstitial nephritis due to oxalate crystal deposition,especially without typical risk factors,emphasizes the need for vigilance in clinical practice.
文摘BACKGROUND Short bowel syndrome(SBS)hospitalizations are often complicated with sepsis.There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe.AIM To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States.METHODS The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014.The study cohort was further divided based on the presence or absence of sepsis.Trends were identified,and hospitalization characteristics and clinical outcomes were compared.Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed.RESULTS Of 247097 SBS hospitalizations,21.7%were complicated by sepsis.Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8%in 2005 to 23.5%in 2014(P trend<0.0001).Compared to non-septic SBS hospitalizations,septic SBS hospitalizations had a higher proportion of males(32.8%vs 29.3%,P<0.0001),patients in the 35-49(45.9%vs 42.5%,P<0.0001)and 50-64(32.1%vs 31.1%,P<0.0001)age groups,and ethnic minorities,i.e.,Blacks(12.4%vs 11.3%,P<0.0001)and Hispanics(6.7%vs 5.5%,P<0.0001).Furthermore,septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation(0.33%vs 0.22%,P<0.0001),inpatient mortality(8.5%vs 1.4%,P<0.0001),and mean length of stay(16.1 d vs 7.7 d,P<0.0001)compared to the non-sepsis cohort.A younger age,female gender,White race,and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations.CONCLUSION Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.
文摘We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
文摘Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in 'one step', EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.
文摘Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.
文摘An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless of their subspecialty interest,will encounter patients with DM during their career since this epidemic involves both developed and emerging countries.Diabetes results in complications affecting multiple organ systems,potentially resulting in adverse outcomes afterorthopaedic surgery.The purpose of this review is to discuss the pathophysiology of DM and its potential for impacting orthopaedic surgery patients.Diabetes adversely affects the outcome of all orthopaedic surgery subspecialties including foot and ankle,upper extremity,adult reconstructive,pediatrics,spine surgery and sports medicine.Poorly controlled diabetes negatively impacts bone,soft tissue,ligament and tendon healing.It is the complications of diabetes such as neuropathy,peripheral artery disease,and end stage renal disease which contributes to adverse outcomes.Well controlled diabetic patients without comorbidities have similar outcomes to patients without diabetes.Orthopaedic surgeons should utilize consultants who will assist in inpatient glycemic management as well as optimizing long term glycemic control.
文摘A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timization problems and the increasing importance of low cost distributed parallel environments,it is a natural idea to replace a globar optimization by decentralized local sub-optimizations using GT which introduces the notion of games associated to an optimization problem.The GT/GAs combined optimization method is used for recon-struction and optimization problems by high lift multi-air-foil desing.Numerical results are favorably compared with single global GAs.The method shows teh promising robustness and efficient parallel properties of coupled GAs with different game scenarios for future advanced multi-disciplinary aerospace techmologies.
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
基金We acknowledge the World Climate Research Programme's Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modeling groups (listed in Table l) for producing and making available their model output. This research is supported by the National Key Research and Development Program of China (2017YFA0603804) and the State Key Program of National Natural Science Foundation of China (41230528).
文摘The long-term goal of the 2015 Paris Agreement is to limit global warming to well below 2 ℃above pre-industrial levels and to pursue efforts to limit it to 1.5 ℃. However, for climate mitigation and adaption efforts, further studies are still needed to understand the regional consequences between the two global warming limits. Here we provide an assessment of changes in temperature extremes over China (relative to 1986-2005) at 1.5 ℃ and 2 ℃ warming levels (relative to 1861-1900) by using the 5th phase of the Coupled Model Intercomparison Project (CMIP5) models under three RCP scenarios (RCP2.6, RCP4.5, RCP8.5). Results show that the increases in mean temperature and temperature extremes over China are greater than that in global mean temperature. With respect to 1986-2005, the temperature of hottest day (TXx) and coldest night (TNn) are projected to increase about 1/1.6 ℃ and 1.1/1.8 ℃, whereas warm days (TX90p) and warm spell duration (WSDI) will increase about 7.5/13.8% and 15/30 d for the 1.5/2 ℃ global warming target, respectively. Under an additional 0.5 ℃ global warming, the projected increases of temperature in warmest day/night and coldest day/night are both more than 0.5 ℃ across almost the whole China. In Northwest China, Northeast China and the Tibetan Plateau, the projected changes are particularly sensitive to the additional 0.5 ℃ global warming, for example, multi-model mean increase in coldest day (TXn) and coldest night (TNn) will be about 2 times higher than a change of 0.5 ℃ global warming. Although the area-averaged changes in temperature extremes are very similar for different scenarios, spatial hotspot still exists, such as in Northwest China and North China, the increases in temperatures are apparently larger in RCP8.5 than that in RCP4.5.