Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study.

OBJECTIVE: It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis. DESIGN: We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005-2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn's disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed. RESULTS: 1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001). CONCLUSIONS: Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.

Changes in incidence and clinical features of inflammatory bowel disease in Cardiff, UK over 50 years: an update for 2005-2016.

INTRODUCTION: Population-based studies of inflammatory bowel disease (IBD) in Cardiff have recorded data back to 1930 for Crohn's disease (CD) and 1968 for ulcerative colitis (UC). This study compares incidence and phenotype for 2005-2016 with past data. METHODS: All new IBD cases resident in the Cardiff at diagnosis were collected retrospectively for the 12-year period 2005-2016, and compared with previous Cardiff data for trends in incidence and phenotype. Overall incidence was age/sex corrected to the UK population. RESULTS: There were 991 new patients: 34% had CD, 5.4% IBD unclassified (IBD-U) and 60.5% had UC. The corrected incidence of CD was 7.7 per 100,000 person years [95% CI 6.9-8.6]. CD incidence is significantly higher than previous Cardiff studies, but the annual percentage change (APC) for 1980-2016 of 0.06; [95%CI -0.02 to 0.14] is not significant, with a previous higher APC for 1953-1980 of 0.18, [95%CI 0.13 to 0.23]. Uncorrected IBD-U incidence was 1.3 per 100,000 person years [95% CI 1.0-1.7]. UC corrected incidence was 14.4 per 100,000 person years [95% CI 13.3-15.6]. Incidence of UC is greater than in previous studies but did not increase during the current 12-year period. CD distribution at diagnosis continues to change as in previous Cardiff studies, with further increase in colonic disease and ileocolonic, (42% L2, 28% L3) and reduction in isolated terminal ileal disease (29% L1). CONCLUSIONS: Incidence of both CD and UC are no longer rising significantly, but the location of CD at diagnosis continues to change with an increase in colonic location.Key messagesWhat is already known? It is unclear whether the incidence of IBD has now plateaued in urbanised nations. Changes in Crohn's disease location are often not reported in incidence studies and terminal ileal disease has usually been reported as the commonest site of diseaseWhat is new here? The incidence of UC and Crohn's is no longer rising in Cardiff UK, but the phenotype has changed progressively over time with a continuing increase in colonic disease location and decrease in isolated terminal ileal diseaseHow can this study help patient care? Understanding that Crohn's colitis is the predominant location has implications for diagnostic tests and implications for treatment optionsIMPACT STATEMENTThis work shows that although IBD incidence is no longer rising, the pattern of Crohn's disease is changing with more colonic disease and less isolated terminal ileal disease.PRACTITIONER RELEVANCE STATEMENTThe changing pattern of Crohn's disease location has implications for diagnostic assessment and treatment of this disease.

Axenfeld-Rieger syndrome: more than meets the eye.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition. METHODS: Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses. RESULTS: 128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of FOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS. CONCLUSION: Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.

Novel PAX6 variant in a family with ophthalmologic, pancreatic, and olfactory features.

Variants in the PAX6 gene have been associated with ophthalmologic, neurologic, and pancreatic differences. We report on a proband, mother, and affected brother who presented with congenital cataracts and glaucoma at a young age. Nonocular findings are also reported among these family members. After a congenital cataracts next-generation sequencing (NGS) gene panel was found to be nondiagnostic in 2016, a more expanded panel in 2020 revealed a novel variant: c.178T > A; p.Tyr60Asn in exon 6 of the PAX6 gene in the proband. The variant is also present in the affected mother and affected brother; it is absent in an unaffected brother. The clinical findings of these three relatives, in conjunction with their genetic testing and the associated PAX6 features reported in the literature, suggest that this novel familial variant may be an underlying etiology for these individuals' ophthalmologic, pancreatic, and olfactory symptoms.

A Novel Automated System Yields Reproducible Temporal Feeding Patterns in Laboratory Rodents.

BACKGROUND: The impact of temporal feeding patterns remains a major unanswered question in nutritional science. Progress has been hampered by the absence of a reliable method to impose temporal feeding in laboratory rodents, without the confounding influence of food-hoarding behavior. OBJECTIVE: The aim of this study was to develop and validate a reliable method for supplying crushed diets to laboratory rodents in consistent, relevant feeding patterns for prolonged periods. METHODS: We programmed our experimental feeding station to deliver a standard diet [StD; Atwater Fuel Energy (AFE) 13.9% fat] or high-fat diet (HFD; AFE 45% fat) during nocturnal grazing [providing 1/24th of the total daily food intake (tdF/I) of ad libitum-fed controls every 30 min] and meal-fed (3 × 1-h periods of ad libitum feeding) patterns in male rats (Sprague-Dawley: 4 wk old, 72-119 g) and mice [C57/Bl6J wild-type (WT): 6 mo old, 29-37 g], and ghrelin-null littermates (Ghr-/-; 27-34 g). RESULTS: Grazing yielded accurate, consistent feeding events in rats, with an approximately linear rise in nocturnal cumulative food intake [tdF/I (StD): 97.4 ± 1.5% accurate compared with manual measurement; R2 = 0.86; tdF/I (HFD): 99.0 ± 1.4% accurate; R2 = 0.86]. Meal-feeding produced 3 nocturnal meals of equal size and duration in StD-fed rats (tdF/I: 97.4 ± 0.9% accurate; R2 = 0.90), whereas the second meal size increased progressively in HFD-fed rats (44% higher on day 35 than on day 14; P < 0.01). Importantly, cumulative food intake in grazing and meal-fed rats was identical. Similar results were obtained in WT mice except that less restricted grazing induced hyperphagia (compared with meal-fed WT mice; P < 0.05 from day 1). This difference was abolished in Ghr-/- mice, with meal initiation delayed and meal duration enhanced. Neither pattern elevated corticosterone secretion in rats, but meal-feeding aligned ultradian pulses. CONCLUSIONS: We have established a consistent, measurable, researcher-defined, stress-free method for imposing temporal feeding patterns in rats and mice. This approach will facilitate progress in understanding the physiologic impact of feeding patterns.

Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases.

PURPOSE: Limb-girdle muscular dystrophies (LGMD) are a genetically heterogeneous category of autosomal inherited muscle diseases. Many genes causing LGMD have been identified, and clinical trials are beginning for treatment of some genetic subtypes. However, even with the gene-level mechanisms known, it is still difficult to get a robust and generalizable prevalence estimation for each subtype due to the limited amount of epidemiology data and the low incidence of LGMDs. METHODS: Taking advantage of recently published exome and genome sequencing data from the general population, we used a Bayesian method to develop a robust disease prevalence estimator. RESULTS: This method was applied to nine recessive LGMD subtypes. The estimated disease prevalence calculated by this method was largely comparable with published estimates from epidemiological studies; however, it highlighted instances of possible underdiagnosis for LGMD2B and 2L. CONCLUSION: The increasing size of aggregated population variant databases will allow for robust and reproducible prevalence estimates of recessive disease, which is critical for the strategic design and prioritization of clinical trials.

ClinGen's RASopathy Expert Panel consensus methods for variant interpretation.

PURPOSE: Standardized and accurate variant assessment is essential for effective medical care. To that end, Clinical Genome (ClinGen) Resource clinical domain working groups (CDWGs) are systematically reviewing disease-associated genes for sufficient evidence to support disease causality and creating disease-specific specifications of American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines for consistent and accurate variant classification. METHODS: The ClinGen RASopathy CDWG established an expert panel to curate gene information and generate gene- and disease-specific specifications to ACMG-AMP variant classification framework. These specifications were tested by classifying 37 exemplar pathogenic variants plus an additional 66 variants in ClinVar distributed across nine RASopathy genes. RESULTS: RASopathy-related specifications were applied to 16 ACMG-AMP criteria, with 5 also having adjustable strength with availability of additional evidence. Another 5 criteria were deemed not applicable. Key adjustments to minor allele frequency thresholds, multiple de novo occurrence events and/or segregation, and strength adjustments impacted 60% of variant classifications. Unpublished case-level data from participating laboratories impacted 45% of classifications supporting the need for data sharing. CONCLUSION: RAS-specific ACMG-AMP specifications optimized the utility of available clinical evidence and Ras/MAPK pathway-specific characteristics to consistently classify RASopathy-associated variants. These specifications highlight how grouping genes by shared features promotes rapid multigenic variant assessment without sacrificing specificity and accuracy.

Effect of Ibuprofen on Skeletal Muscle of Dysferlin-Null Mice.

Ibuprofen, a nonsteroidal anti-inflammatory drug, and nitric oxide (NO) donors have been reported to reduce the severity of muscular dystrophies in mice associated with the absence of dystrophin or α-sarcoglycan, but their effects on mice that are dystrophic due to the absence of dysferlin have not been examined. We have tested ibuprofen, as well as isosorbide dinitrate (ISDN), a NO donor, to learn whether used alone or together they protect dysferlin-null muscle in A/J mice from large strain injury (LSI) induced by a series of high strain lengthening contractions. Mice were maintained on chow containing ibuprofen and ISDN for 4 weeks. They were then subjected to LSI and maintained on the drugs for 3 additional days. We measured loss of torque immediately following injury and at day 3 postinjury, fiber necrosis, and macrophage infiltration at day 3 postinjury, and serum levels of the drugs at the time of euthanasia. Loss of torque immediately after injury was not altered by the drugs. However, the torque on day 3 postinjury significantly decreased as a function of ibuprofen concentration in the serum (range, 0.67-8.2 µg/ml), independent of ISDN. The effects of ISDN on torque loss at day 3 postinjury were not significant. In long-term studies of dysferlinopathic BlAJ mice, lower doses of ibuprofen had no effects on muscle morphology, but reduced treadmill running by 40%. Our results indicate that ibuprofen can have deleterious effects on dysferlin-null muscle and suggest that its use at pharmacological doses should be avoided by individuals with dysferlinopathies.

Fatal and Non-Fatal Electrocution Injuries at U.S. Marine Corps Forward Medical Facilities During Operation Enduring Freedom and Operation Iraqi Freedom.

INTRODUCTION: Death from electrocution is rare and generally an accidental occurrence. In contrast to civilian patterns of electrocution injury, the military work environment suffers from a greater percentage of fatal high-voltage electrocutions. This study compared U.S. and international electrocution case fatality rates to rates among deployed military personnel presenting for care at expeditionary medical care facilities. We also sought to identify potential risk factors for fatal electrocution injury among deployed military personnel. MATERIALS AND METHODS: A retrospective analysis was performed on electrocution injuries presenting to U.S. Marine Corps forward deployed medical facilities in Iraq and Afghanistan between January 2004 and December 2012. Descriptive statistics were used to describe the study population and compare fatal and nonfatal electrocutions. Fatality rates were reported in cases per 1,000,000 people per year. RESULTS: A total of 38 patients were identified; all were males with a mean (SD) age of 25.3 (5.3) years. Most electrocutions occurred on base (68%), whereas a smaller number (21%) occurred while conducting operations outside of the base. A majority of fatal cases (80%) occurred while outside of base on foot or vehicle mounted patrol. The rate of fatal electrocutions among U.S. Marine Corps personnel during this period was 37 per 1,000,000 people per year, 7-fold higher than the international electrocution fatality rate of 5.4 per 1,000,000 people per year and nearly three-fold above the U.S. utility and construction worker's fatality rate of 14 per 1,000,000 people per year. CONCLUSIONS: Electrocution injuries occurring during foot or vehicle mounted patrols seem to account for findings of higher case fatality rates among deployed military personnel than those found in international or high risk civilian occupational settings. Basic life support training for medical and nonmedical military personnel is critical to optimizing care delivered at the scene of these injuries.

Hormone Replacement: The Fountain of Youth?

Natural aging brings reduced production of growth and sex hormones, beginning in middle age, with noticeable physiologic changes by the sixth or seventh decade of life: reduced muscle mass, energy, and exercise capacity and alterations in sexual function. Hormones and hormone precursors have been investigated to delay changes in body composition, strength, and physical and cognitive function. Menopausal hormone therapy is effective for vasomotor and genitourinary symptoms. Testosterone is effective in men with hypogonadism and declines in physiologic function. The lack of clinical studies evaluating the long-term effects and risks of hormone replacement limits its use.

Effects of Single and Multiple Energy Shots on Blood Pressure and Electrocardiographic Parameters.

We assessed the effects of single and multiple caffeinated energy shots on hemodynamic and electrocardiographic (ECG) parameters. This was a randomized, double-blinded, placebo-controlled, crossover study in otherwise healthy volunteers (n = 26) where a caffeinated energy shot or matching placebo was ingested. The study drink was consumed twice daily for 7 days during each phase, with a 7-day washout period in between. The primary end points of interest were systolic and diastolic blood pressure (BP), heart rate, PR interval, QRS duration, and QT and QTc intervals. All parameters were evaluated at baseline, 1, 3, and 5 hours on the first and seventh day of each phase. Systolic BP after a single energy shot consumption was significantly higher than placebo at 3 and 5 hours (p = 0.050 and p = 0.038, respectively). Similarly, diastolic BP after a single energy shot consumption was significantly higher at 1 and 5 hours (p = 0.019 and p = 0.043, respectively). The systolic and diastolic BP elevations were not significant after consistent consumption (all p values ≥ 0.079). None of the ECG parameters were significantly affected (all p values ≥ 0.108) compared with placebo. In conclusion, a single shot of a caffeinated energy drink significantly raised systolic and diastolic BPs. However, these elevations were not sustained with chronic consumption. ECG parameters were not altered.

Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis.

STUDY QUESTION: Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? METHODS: This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465,918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4,355,418 person quarters); 71,895 (15.4%) patients also filled a prescription for warfarin (416,479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status. SUMMARY ANSWER AND LIMITATIONS: In quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416,479 v 1903/3,938,939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416,479 v 20,759/3,938,939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416,479 v 14,414/3,938,939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and serious hypoglycemic events, leading to confounding. The findings may not generalize beyond the elderly Medicare population. WHAT THIS STUDY ADDS: A substantial positive association was seen between use of warfarin with glipizide/glimepiride and hospital admission/emergency department visits for hypoglycemia and related diagnoses, particularly in patients starting warfarin. The findings suggest the possibility of a significant drug interaction between these medications. FUNDING, COMPETING INTERESTS, DATA SHARING: JAR and DPG receive support from the National Institute on Aging, the Commonwealth Fund, and the Leonard D. Schaeffer Center for Health Policy and Economics at the University of Southern California. ABJ receives support from the NIH Office of the Director. No additional data are available.

Sun exposure knowledge and practices survey of maintenance squadrons at Travis AFB.

Recent literature has shown that the incidence of melanoma skin cancer is significantly higher in the U.S. military than for civilians and is higher in the U.S. Air Force than other military branches. No studies have investigated military specific exposures that might increase this risk. Using a cross-sectional survey we evaluated sun exposure knowledge and practices of U.S. Air Force flight line workers whose duties may lead to increased melanoma risk. The specific aims of this study were to (1) describe the social demographic characteristics of maintenance personnel, (2) describe current sun blocking practices in maintenance personnel, (3) describe knowledge about sun exposure risks and benefits, and (4) identify factors influencing practices that increase the risk for developing melanoma. Our survey of 356 Air Force flight line personnel showed that 67% of their career required working in direct sunlight, 94.7% of personnel know that it is recommended to use sun blocking methods, yet the majority do not regularly use sun protective measures. Our results suggest that the increased incidence of melanoma in the U.S. Air Force may be due to the type or duration of ultraviolet exposure.

Assaults on Inmates and Staff by Perpetrators of Intimate Partner Homicide: An Examination of Competing Hypotheses.

The current study presents the results of an analysis of serious and assaultive prison rule violating behavior among male perpetrators of intimate partner homicide (IPH). Data on prison rule violations were collected from a sample of 189 inmates convicted of IPH in a large, southern prison system. The study focused on the degree of continuity in violent behavior among IPH offenders from the community to the prison setting. The current study tested hypotheses derived from both the feminist perspective (FP) and the general violence perspective (GVP). As a group, IPH offenders were better behaved in prison than other incarcerated homicide offenders, thereby offering some support for the FP. However, the lower level of assaultive behavior among the group was not universal. Characteristics associated with continued violent offending in the prison environment were the same as those found in previous studies of incarcerated homicide offenders, thereby lending greater support to the GVP.

6th Dysferlin Conference, 3-6 April 2013, Arlington, Virginia, USA.

The 2013 Dysferlin Conference, sponsored and organized by the Jain Foundation, was held from April 3-6, 2013 in Arlington, VA. Participants included 34 researcher speakers, 5 dysferlinopathy patients and all 8 members of the Jain Foundation team. Dysferlinopathy is a rare disease that typically robs patients of mobility during their second or third decade of life. The goals of these Dysferlin Conferences are to bring experts in the field together so that they will collaborate with one another, to quicken the pace of understanding the biology of the disease and to build effective platforms to ameliorate disease. This is important because the function of dysferlin and how to compensate for its absence is still not well understood, in spite of the fact that the dysferlin gene was identified more than a decade ago. The objective of this conference, therefore, was to share and discuss the newest unpublished research defining the role of dysferlin in skeletal muscle, why its absence causes muscular dystrophy and possible therapies for dysferlin-deficient muscular dystrophy patients.

A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies.

PURPOSE: The only known genetic cause of brachytelephalangic chondrodysplasia punctata is X-linked chondrodysplasia punctata 1 (CDPX1), which results from a deficiency of arylsulfatase E (ARSE). Historically, ARSE mutations have been identified in only 50% of male patients, and it was proposed that the remainder might represent phenocopies due to maternal-fetal vitamin K deficiency and maternal autoimmune diseases. METHODS: To further evaluate causes of brachytelephalangic chondrodysplasia punctata, we established a Collaboration Education and Test Translation program for CDPX1 from 2008 to 2010. Of the 29 male probands identified, 17 had ARSE mutations that included 10 novel missense alleles and one single-codon deletion. To determine pathogenicity of these and additional missense alleles, we transiently expressed them in COS cells and measured arylsulfatase E activity using the artificial substrate, 4-methylumbelliferyl sulfate. In addition, clinical data were collected to investigate maternal effects and genotype-phenotype correlations. RESULTS: In this study, 58% of males had ARSE mutations. All mutant alleles had negligible arylsulfatase E activity. There were no obvious genotype-phenotype correlations. Maternal etiologies were not reported in most patients. CONCLUSION: CDPX1 is caused by loss of arylsulfatase E activity. Around 40% of male patients with brachytelephalangic chondrodysplasia punctata do not have detectable ARSE mutations or known maternal etiological factors. Improved understanding of arylsulfatase E function is predicted to illuminate other etiologies for brachytelephalangic chondrodysplasia punctata.

Bariatric surgery is associated with a reduction in major macrovascular and microvascular complications in moderately to severely obese patients with type 2 diabetes mellitus.

BACKGROUND: Bariatric surgery (BAR) has been established as an effective treatment for type 2 diabetes mellitus (T2DM) in obese patients. However, few studies have examined the mid- to long-term outcomes of bariatric surgery in diabetic populations. Specifically, no comparative studies have broadly examined major macrovascular and microvascular complications in bariatric surgical patients vs similar, nonbariatric surgery controls. STUDY DESIGN: We conducted a large, population-based, retrospective cohort study of adult obese patients with T2DM, from 1996 to 2009, using UB-04 administrative data and vital records. Eligible patients undergoing bariatric surgery (BAR [n = 2,580]) were compared with nonbariatric surgery controls (CON [n = 13,371]) for the outcomes of any first major macrovascular event (myocardial infarction, stroke, or all-cause death) or microvascular event (new diagnosis of blindness, laser eye or retinal surgery, nontraumatic amputation, or creation of permanent arteriovenous access for hemodialysis), assessed in combination and separately, as well as other vascular events (carotid, coronary or lower extremity revascularization or new diagnosis of congestive heart failure or angina pectoris). RESULTS: Bariatric surgery was associated with favorable unadjusted 5-year event-free survival estimates for the combined primary outcome (95% ± 1% vs 81% ± 1%, log-rank p < 0.01) and each secondary outcome (log-rank p < 0.01). Multivariate-adjusted and propensity-based relative risk estimates showed BAR to be associated with a 60% to 70% reduction (adjusted hazard ratio [HR] 0.36, 95% CI 0.27 to 0.47) in the combined primary outcome and 60% to 80% risk reductions for each secondary outcome (macrovascular events [adjusted HR 0.39, 95% CI 0.29 to 0.51]; microvascular events [adjusted HR 0.22, 95% CI 0.09 to 0.49]; and other vascular events [adjusted HR 0.25, 95% CI 0.19 to 0.32]). CONCLUSIONS: Bariatric surgery is associated with a 65% reduction in major macrovascular and microvascular events in moderately and severely obese patients with T2DM.

Automated riverine landscape characterization: GIS-based tools for watershed-scale research, assessment, and management.

River systems consist of hydrogeomorphic patches (HPs) that emerge at multiple spatiotemporal scales. Functional process zones (FPZs) are HPs that exist at the river valley scale and are important strata for framing whole-watershed research questions and management plans. Hierarchical classification procedures aid in HP identification by grouping sections of river based on their hydrogeomorphic character; however, collecting data required for such procedures with field-based methods is often impractical. We developed a set of GIS-based tools that facilitate rapid, low cost riverine landscape characterization and FPZ classification. Our tools, termed RESonate, consist of a custom toolbox designed for ESRI ArcGIS®. RESonate automatically extracts 13 hydrogeomorphic variables from readily available geospatial datasets and datasets derived from modeling procedures. An advanced 2D flood model, FLDPLN, designed for MATLAB® is used to determine valley morphology by systematically flooding river networks. When used in conjunction with other modeling procedures, RESonate and FLDPLN can assess the character of large river networks quickly and at very low costs. Here we describe tool and model functions in addition to their benefits, limitations, and applications.

Critical Role for hierarchical geospatial analyses in the design of fluvial research, assessment, and management.

River science and management can be conducted at a range of spatiotemporal scales from reach to basin levels as long as the project goals and questions are matched correctly with the study design's spatiotemporal scales and dependent variables. These project goals should also incorporate information on the hydrogeomorphically patchy nature of riverine macrosystems which is only partially predictable in type and location from a river's headwaters to its terminus. This patchiness significantly affects a river's habitat template, and thus community structure, ecosystem function, and responses to perturbations. Our manuscript is designed for use by senior administrators at government agencies through entry-level river scientists. It analyzes common challenges in project design and recommends solutions based partially on hierarchical analyses that combine geographic information systems and multivariate statistical analysis to enable self-emergence of a stream's patchy structure. These approaches are useful at all spatial levels and can vary from primary reliance on geospatial techniques at the valley level to a greater dependence on field-based measurements and expert opinion at the reach level. Comparative uses of functional process zones (FPZs = valley-scale hydrogeomorphic patches), ecoregions, hydrologic unit codes, and reaches in project designs are discussed along with other comparative approaches for stream classification and analysis of species distributions (e.g., GAP analysis). Use of hierarchical classification of patch structure for sample stratification, reference site selection, ecosystem services, rehabilitation, and mitigation are briefly explored.