Laboratory or Department?Exploration and Creation in Computer Science and Technology

In the very beginning,the Computer Laboratory of the University of Cambridge was founded to provide computing service for different disciplines across the university.As computer science developed as a discipline in its own right,boundaries necessarily arose between it and other disciplines,in a way that is now often detrimental to progress.Therefore,it is necessary to reinvigorate the relationship between computer science and other academic disciplines and celebrate exploration and creativity in research.To do this,the structures of the academic department have to act as supporting scaffolding rather than barriers.Some examples are given that show the efforts being made at the University of Cambridge to approach this problem.

Ending Privacy’s Gremlin: Stopping the Data-Broker Loophole to the Fourth Amendment’s Search Warrant Requirement

Advances in technology require upgrades in the law. One such area involves data brokers, which have thus far gone unregulated. Data brokers use artificial intelligence to aggregate information into data profiles about individual Americans derived from consumer use of the internet and connected devices. Data profiles are then sold for profit. Government investigators use a legal loophole to purchase this data instead of obtaining a search warrant, which the Fourth Amendment would otherwise require. Consumers have lacked a reasonable means to fight or correct the information data brokers collect. Americans may not even be aware of the risks of data aggregation, which upends the test of reasonable expectations used in a search warrant analysis. Data aggregation should be controlled and regulated, which is the direction some privacy laws take. Legislatures must step forward to safeguard against shadowy data-profiling practices, whether abroad or at home. In the meantime, courts can modify their search warrant analysis by including data privacy principles.

Epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study

BACKGROUND Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types:Supracondylar(SC),lateral condyle(LC),and medial epicondyle(ME)fractures.AIM To evaluate the epidemiology of pediatric distal humerus fractures(SC,LC,and ME)from an American insurance claims database.METHODS A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC,LC and ME fractures based on the IBM Truven MarketScan®Commercial and IBM Truven MarketScan Medicare Supplemental databases.Patients from 2015 to 2020 were queried for treatments,patient age,sex,length of hospitalization,and comorbidities.RESULTS A total of 1133 SC,154 LC,and 124 ME fractures were identified.SC fractures had the highest percentage of operation at 83%,followed by LC(78%)and ME fractures(41%).Male patients were,on average,older than female patients for both SC and ME fractures.CONCLUSION In the insurance claims databases used,SC fractures were the most reported,followed by LC fractures,and finally ME fractures.Age was identified to be a factor for how a pediatric distal humerus fractures,with patients with SC and LC fractures being younger than those with ME fractures.The peak age per injury per sex was similar to reported historic central tendencies,despite reported trends for younger physiologic development.

Reimagining critical care:Trends and shifts in 21st century medicine

primarily driven by advancements in technology,changes in healthcare delivery,and a deeper understanding of disease processes.Advancements in technology have revolutionized patient monitoring,diagnosis,and treatment in the critical care setting.From minimally invasive procedures to advances imaging techniques,clinicians now have access to a wide array of tools to assess and manage critically ill patients more effectively.In this editorial we comment on the review article published by Padte S et al wherein they concisely describe the latest developments in critical care medicine.

Chemical Determination of Base Status Metals in Soil Sediments and Particulate Matter in Wellington Industrial Estate Location

This research study explored the levels of base status metals in soil sediments and particulate matter in the wellington industrial estate location;the main objectives were to: 1) determine sodium and potassium, 2) determine calcium and magnesium, 3) determine available iron. The following hypotheses were put forward;H0a: there is no significant difference in the concentration levels between Ca and Mg in the study area, H1a: there is significant difference in the concentration levels between Ca and Mg in the study area, H0b: there is no significant difference in the concentration levels between Na and K in the study area, H1b: there is significant difference in the concentration levels between Na and K in the study area. Six locations were used to collect samples with the aid of scoop and gravel free auger (at varying depths of 0 - 5 cm and 5 - 10 cm) which are Wellington Industrial Estate Area 1 (WIEL 1), (WIEL 2), (WIEL 3), (WIEL 4), (WIEL 5), (WIEL 6);the samples were given laboratory treatment. Flame photometer, EDTA, and Spectrophotometer were used in the determinations of sodium and potassium, calcium and magnesium, and available iron respectively. The results indicated that levels of potassium were in medium range (moderately high);sodium levels were generally low when compared to Brook’s classification table. Levels of calcium were generally low and those of magnesium were moderate based on Brook’s table of classification. Levels of available iron which fall within the range of Quijano-Guerta (2003) were high;this implies such levels can lead to toxicity. In all locations, there was decrease in the levels of each metal in the samples with (5 - 10 cm) depth.

Dynamics of Potable Well Water Quality in Key Mining Chiefdoms in Kono District, Eastern Sierra Leone

Groundwater is increasingly being used due to its universal availability and generally good quality. However, the risk of contamination of groundwater due to various human activities such as mining is equally increasing across the globe. In this study, the physical parameters of potable well waters in the key mining areas in Nimikoro and Tankoro Chiefdoms in Kono District were analyzed for compliance with drinking water quality standard. To do this, both unpurged and purged well water samples were collected once every month for a period of one year. Some of the well water properties like temperature, Total Dissolved Solids (TDS) and Electrical Conductivity (EC) were measured on site and others determined in the laboratory. The data collected from the laboratory analyses were statistically analyzed in MS Excel, SPSS and ArcGIS environments for quality trends in time-space fabric. The results showed that well water quality in the study area generally fell short of drinking water quality standards of Sierra Leone and WHO. There were high temperature and turbidity during the dry season and then high TDS and EC during the rainy season. Temperature and turbidity also significantly influenced well water quality in the study area, much more than TDS and EC. The implications for drinking water of lower quality than the standard could be huge for the local population and therefore needs the attention of stakeholders in the study area and decision makers in the country.

Omega-3多不饱和脂肪酸与早产儿

近 10多年来 ,关于Omega - 3多不饱和脂肪酸在早产儿神经及视功能发育中的研究已经有了相当的进展。早产儿随机临床试验对这一领域的发展做了较为详尽的阐述。发现Omega - 3多不饱和脂肪酸的添加有益于早产儿神经及视功能的发育 ,但也发现它对早产儿的生长发育有一定的副作用 ,而同时添加AA减少了不利影响。某些混淆因素如出生前早产儿母亲皮质激素的注射可能影响研究结果。在提倡早产儿饮食中添加Omega - 3多不饱和脂肪酸之前我们还需要更多的研究 ,以追踪及评估婴幼儿的长期预后。

一种高质量葡萄基因组DNA提取方法

针对葡萄组织中多酚、多糖类物质含量较高的特点,对比研究了利用植物总DNA提取试剂盒和改良CTAB法提取葡萄总DNA。结果表明:改良的CTAB法能够从不同葡萄品种和不同生长时期的叶片中获得高质量、完整性好的总DNA,其OD260/OD280介于1.7～1.9之间,无降解现象,RNA去除干净,完全适于进行PCR和酶切等研究。

Portal hypertensive gastropathy:A systematic review of thepathophysiology,clinical presentation,natural history andtherapy

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature review.METHODS: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG.PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepaticportosystemic-shunt or liver transplantation is highly successful ultimate therapies because they reduce the underlying portal hypertension.CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

Distinctive aspects of peptic ulcer disease,Dieulafoy'slesion,and Mallory-Weiss syndrome in patients withadvanced alcoholic liver disease or cirrhosis

AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.

Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy

Primary biliary cirrhosis(PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies(AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis(AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

Liver transplantation: Current status and challenges

Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death(DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function.

Therapy for alcoholic liver disease

Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.

Infections in liver transplant recipients

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications.In this article,we review the contemporary state of infectious complications during the post-operative period,with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation.Bacteria,and less commonly Candida infections,remain the predominant pathogens during the immediate post-operative period,especially during the first month,and infections caused by drugresistant strains are emerging.Infections caused by cytomegalovirus and Aspergillus sp.present clinically during the'opportunistic'period characterized by intense immunosuppression.As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed,one potential adverse effect is an increase in certain infections.Hence,it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk,local antimicrobial resistance patterns,and surveillance.A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

Cytomegalovirus infection after liver transplantation: Current concepts and challenges

Cytomegalovirus (CMV) is a common viral pathogen that influences the outcome of liver transplantation. In addition to the direct effects of CMV syndrome and tissue-invasive diseases, CMV is associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. Risk factors for CMV disease are often interrelated, and include CMV D+/R-serostatus, acute rejection, female gender, age, use of high-dose mycophenolate mofetil and prednisone, and the overall state of immunity. In addition to the role of CMV-specif ic CD4+ and CD8+ T lymphocytes, there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis. In one study, liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher levels of CMV replication and clinical disease. Because of the direct and indirect adverse effects of CMV disease, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component in improving the outcome of liver transplantation. In the majority of transplant centers, antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-). However, the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease. In several prospective and retrospective studies, the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention and novel drugs with unique modes of action are needed. Currently, a randomized controlled clinical trial is being performed comparing the effi cacy and safety of maribavir, a novel benzimidazole riboside, and oral ganciclovir as prophylaxis against primary CMV disease in liver transplant recipients. The treatment of CMV disease consists mainly of intravenous (IV) ganciclovir, and if feasible, a reduction in the degree of immunosuppression. A recent controlled clinical trial demonstrated that valganciclovir is as effective and safe as IV ganciclovir for the treatment of CMV disease in solid organ (including liver) transplant recipients. In this article, the author reviews the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

Stricter national standards are required for credentialing of endoscopic-retrograde-cholangiopan-creatography in the United States

Endoscopic-retrograde-cholangiopancreatography(ERCP) is now a vital modality with primarily therapeutic and occasionally solely diagnostic utility for numerous biliary/pancreatic disorders. It has a significantly steeper learning curve than that for other standard gastrointestinal(GI) endoscopies, such as esophagogastroduodenoscopy or colonoscopy, due to greater technical difficulty and higher risk of complications. Yet, GI fellows have limited exposure to ERCP during standard-three-year-GI-fellowships because ERCP is much less frequently performed than esophagogastroduodenoscopy/colonoscopy. This led to adding an optional year of training in therapeutic endoscopy. Yet many graduates from standard three-year-fellowships without advanced training intensely pursue independent/unsupervised ERCP privileges despite inadequate numbers of performed ERCPs and unacceptably low rates of successful selective cannulation of desired(biliary or pancreatic) duct. Hospital credentialing committees have traditionally performed ERCP credentialing, but this practice has led to widespread flouting of recommended guidelines(e.g., planned privileging of applicant with 20% successful cannulation rate, or after performing only 7 ERCPs);and intense politicking of committee members by applicants, their practice groups, and potential competitors. Consequently, some gastroenterologists upon completing standard fellowships train and learn ERCP 'on the job' during independent/unsupervised practice, which can result in bad outcomes: high rates of failed bile duct cannulation. This severe clinical problem is indicated by publication of ≥ 12 ERCP competency studies/guidelines during last 5 years. However, lack of mandatory, quantitative, ERCP credentialing criteria has permitted neglect of recommended guidelines. This work comprehensively reviews literature on ERCP credentialing;reviews rationales for proposed guidelines;reports problems with current system;and proposes novel criteria for competency. This work advocates for mandatory, national, written,minimum, quantitative, standards, including cognitive skills(possibly assessed by a nationwide examination), and technical skills, assessed by number performed(≥ 200-250 ERCPs), types of ERCPs, success rate(approximately ≥ 90%cannulation of desired duct), and letters of recommendation by program director/ERCP mentor. Mandatory criteria should ideally not be monitored by a hospital committee subjected to intense politicking by applicants, their employers, and sometimes even competitors, but an independent national entity,like the National Board of Medical Examiners/American Board of Internal Medicine.

Gastrointestinal bleeding from Dieulafoy's lesion: Clinical presentation, endoscopic findings, and endoscopic therapy

Although relatively uncommon, Dieulafoy's lesion is an important cause of acute gastrointestinal bleeding due to the frequent difficulty in its diagnosis; its tendency to cause severe, life-threatening, recurrent gastrointestinal bleeding; and its amenability to life-saving endoscopic therapy. Unlike normal vessels of the gastrointestinal tract which become progressively smaller in caliber peripherally, Dieulafoy's lesions maintain a large caliber despite their peripheral, submucosal, location within gastrointestinal wall. Dieulafoy's lesions typically present with severe, active, gastrointestinal bleeding, without prior symptoms; often cause hemodynamic instability and often require transfusion of multiple units of packed erythrocytes. About 75% of lesions are located in the stomach, with a marked proclivity of lesions within 6 cm of the gastroesophageal junction along the gastric lesser curve, but lesions can also occur in the duodenum and esophagus. Lesions in the jejunoileum or colorectum have been increasingly reported. Endoscopy is the first diagnostic test, but has only a 70% diagnostic yield because the lesions are frequently small and inconspicuous. Lesions typically appear at endoscopy as pigmented protuberances from exposed vessel stumps, with minimal surrounding erosion and no ulceration(visible vessel sans ulcer). Endoscopic therapy, including clips, sclerotherapy, argon plasma coagulation, thermocoagulation, or electrocoagulation, is the recommended initial therapy, with primary hemostasis achieved in nearly 90% of cases. Dual endoscopic therapy of epinephrine injection followed by ablative or mechanical therapy appears to be effective. Although banding is reportedly highly successful, it entails a small risk of gastrointestinal perforation from banding deep mural tissue. Therapeutic alternatives after failed endoscopic therapy include repeat endoscopic therapy, angiography, or surgical wedge resection. The mortality has declined from about 30% during the 1970's to 9%-13% currently with the advent of aggressive endoscopic therapy.

Acute liver failure secondary to severe systemic disease from fatal hemophagocytic lymphohistiocytosis:Case report and systematic literature review

AIM To systematically review liver disease associated with hemophagocytic lymphohistiocytosis(HLH),propose reasonable contraindications for liver transplantation for liver failure in HLH,and report an illustrative case.METHODS Systematic review according to PRISMA guidelines of hepatic manifestations of HLH using computerizedliterature search via PubMed of articles published since 1980 with keywords("hemophagocytic lymphohistiocytosis" or "HLH") AND("liver" or "hepatic"). Two authors independently performed literature search and incorporated articles into this review by consensus. Illustrative case report presented based on review of medical chart,and expert re-review of endoscopic photographs,radiologic images,and pathologic slides. RESULTS A 47-year-old Caucasian male,was hospitalized with high-grade pyrexia,rash,total bilirubin = 45 g/dL,moderately elevated hepatic transaminases,ferritin of 3300 ng/dL,leukopenia,and profound neutropenia(absolute neutrophil count < 100 cells/mm3). Viral serologies for hepatitis A,B,and C were negative. Abdominal computed tomography scan and magnetic resonance imaging revealed no hepatic or biliary abnormalities. Pathologic analysis of liver biopsy revealed relatively well-preserved hepatic parenchyma without lymphocytic infiltrates or macrophage invasion,except for sparse,focal hepatocyte necrosis. Bone marrow biopsy and aspirate revealed foamy macrophages engulfing mature and precursor erythrocytes,consistent with HLH. Interleukin-2 receptor(CD25) was highly elevated,confirming diagnosis of HLH according to Histiocytic Society criteria. Patient initially improved after high-dose prednisone therapy. Patient was judged not to be a liver transplant candidate despite model for end stage liver disease(MELD) score = 33 because liver failure was secondary to severe systemic disease from HLH,including septic shock,focal centrilobular hepatocyte necrosis from hypotension,bone marrow failure,and explosive immune activation from HLH. The patient eventually succumbed to overwhelming sepsis,progressive liver failure,and disseminated intravascular coagulopathy. Systematic review reveals liver injury is very common in HLH,and liver failure can sometimes occur. Data on liver transplantation for patients with HLH are very limited,and so far the results have shown a generally much worse prognosis than for other liver transplant indications. Liver transplantation should not be guided solely by MELD score,but should include liver biopsy results and determination whether liver failure is from intrinsic liver injury vs multisystem(extrahepatic) organ failure from HLH.CONCLUSION This case report illustrates that liver transplantation may not be warranted when liver failure associated with HLH is primarily from multisystem failure from HLH. Liver biopsy may be very helpful in determining the severity and pathophysiology of the liver disease.

Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma

Non-alcoholic fatty liver disease(NAFLD) associated hepatocellular carcinoma(HCC) incidence is increasing worldwide, paralleling the obesity epidemic. Although most cases are associated with cirrhosis, HCC can occur without cirrhosis in NAFLD. Diabetes and obesity are associated risk factors for HCC in patients. Given the sheer magnitude of the underlying risk factors(diabetes, obesity, non-cirrhotic NAFLD) screening for HCC in the non-cirrhotic population is not recommended. Optimal screening strategies in NAFLD cirrhosis are not completely elucidated with Ultrasound having significant limitations in detection of liver lesions in the presence of obesity and steatosis. Consequently NAFLD-HCC is more often diagnosed at a later stage with larger tumors and reduced opportunities for curative treatments as opposed to HCC in other causes of cirrhosis. When HCC is found at a curative stage treatments including liver transplantation, resection and loco-regional therapies are associated with good results similar to that seen in HCV-HCC. Future strategies under study include the use of chemopreventive and antioxidant agents to reduce development of cirrhosis and non-alcoholic steatohepatitis(NASH). Strategies to reverse NASH via weight loss, control of associated conditions like diabetes are key strategies in reducing the increasing incidence of NASH-HCC. Novel therapeutic agents for NASH are in trials and if successful in achieving reversal of NASH will be an important strategy in reducing NAFLD-HCC.

Reconsidering Melt-water Pulses 1A and 1B: Global Impacts of Rapid Sea-level Rise

Re-evaluation of the post-glacial sea level derived from the Barbados coral-reef borings suggests slightly revised depth ranges and timing of melt-water pulses MWP-1A (96-76 m, 14.3-14.0 ka cal BP) and 1B (58-45 m, 11.5-11.2 ka cal BP), respectively. Ages of non-reef sea-level indicators from the Sunda Shelf, the East China Sea and Yellow Sea for these two intervals are unreliable because of the well-documented radiocarbon ( 14C) plateau, but their vertical clustering corresponds closely with MWP-1A and 1B depth ranges. Close correlation of the revised sea-level curve with Greenland ice-core data suggests that the 14C plateau may be related to oceanographic-atmospheric changes due to rapid sea-level rise, fresh-water input, and impaired ocean circulation. MWP-1A appears to have occurred at the end of Blling Warm Transition, suggesting that the rapid sea-level rise may have resulted from lateral heat transport from low to high-latitude regions and subsequent abrupt ice-sheet collapses in both North America-Europe and Antarctica. An around 70 mm a -1 transgression during MWP-1A may have increased freshwater discharge to the North Atlantic by as much as an order of magnitude, thereby disturbing thermohaline circulation and initiating the Older Dryas global cooling.