Miracle-dz/UniFAR-FTUs huggingface dataset:
Resource use and costs of branch and central retinal vein occlusion in the elderly

Abstract Objective: To examine the incidence, prevalence, resource use, and costs associated with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in elderly patients. Research design and methods: In a retrospective cohort study of a nationally representative sample of Medicare beneficiaries from 2001 through 2006, the authors identified patients with BRVO (n = 10 682) and CRVO (n = 6236) and controls with hypertension (n = 49 524) and glaucoma (n = 49 569) but no retinal vein occlusion. Incident cases were those with no claims listing a diagnosis for the same type of retinal vein occlusion in the previous 12 months. Prevalence was defined as the number of beneficiaries with a diagnosis of BRVO or CRVO. The authors summed Medicare reimbursements for all claims and used generalized linear models to estimate the effects of BRVO and CRVO on 1-year and 3-year costs compared with hypertension and glaucoma control groups. The authors also examined trends in the use of diagnostic and treatment modalities. Main outcome measures: Resource use (fluorescein angiography, optical coherence tomography, intravitreal injection, laser photocoagulation, and vitrectomy) and direct medical costs (total Medicare reimbursement amounts as recorded on each inpatient, outpatient, home health, skilled nursing, hospice, durable medical equipment, and professional service claim) at 1 year and 3 years. Results: After adjustment for baseline characteristics, BRVO was associated with 16% higher 1-year costs and 12% higher 3-year costs compared with hypertension and 18% higher 1-year costs and 13% higher 3-year costs compared with glaucoma. CRVO was associated with 22% higher 1-year costs and 15% higher 3-year costs compared with hypertension and 24% higher 1-year costs and 16% higher 3-year costs compared with glaucoma. Use of fluorescein angiography and optical coherence tomography increased during the study. Use of intravitreal injections increased from less than 1% of patients overall to greater than 13% for BRVO and 16% for CRVO. The incidence of BRVO declined slightly during the study period, whereas the incidence of CRVO remained relatively flat. Prevalence increased in both groups. Limitations: The results may not be generalizable to younger patients or managed-care beneficiaries. The study included only direct costs to Medicare, not nonmedical expenditures or outpatient prescription medications. Diagnosis and procedure codes may not have been complete. The study could not account for clinical variables, such as the amount of vision loss. It was not feasible to adjust for whether one or both eyes were affected or treated. Conclusions: Although not common in the Medicare population, BRVO and CRVO are important independent predictors of total medical costs. Diagnostic and treatment modalities have changed over time.
The potential demographic significance of unmet need.

Demographic and Health Survey data conducted in the 1990s from 27 countries are used to estimate demand for family planning among currently married women. Potential contraceptive use is measured as the sum of unmet need and contraceptive prevalence among fecund women. Three models of unmet need are constructed. In the first model all unmet need can be satisfied. Contraceptive prevalence and satisfaction of all unmet need would increase in sub-Saharan African countries from 15% to 37%. The rise in other regions was much smaller with the exception of Pakistan where increases would be from 12% to 38%. The second model is the minimum prevalence model and includes current and intended users. About 50% of all married women in the 27 countries expressed a desire to space future births or to end childbearing and an intention not to practice contraception or to be uncertain about using contraception in the future. In the second model prevalence would almost double in some countries and in most sub-Saharan African countries from 15% to 28%. The third model is the most conservative estimate of prevalence and unmet need. The mean value for sub-Saharan countries was 30%. For other countries it was 58%. The correlation between contraceptive prevalence and the fertility rate for 86 countries was 0.94 in unadjusted regression equations. In the adjusted equations fertility would be substantially reduced if unmet need were met. The reduction in sub-Saharan Africa would average 17% and would be 25% with the maximum assumption. With the most conservative fulfillment of unmet need the total fertility rate (TFR) in sub-Saharan countries would decline from 6.1 to 5.1 lifetime births per woman. The expected declines in TFR for other countries under the most realistic and conservative assumptions would average 18%. For some countries meeting unmet demand would result in near or actual replacement fertility.
Economic models in type 2 diabetes

Abstract Objective: To identify and critically appraise cost-effectiveness models developed to evaluate type 2 diabetes (T2D) treatments and to assess which types of treatment effects they capture. Research design and methods: A systematic search was performed in MEDLINE, EMBASE, Centre for Reviews and Dissemination databases at the University of York, and Health Economic Evaluation Database for the period to September 2008. The websites of Health Technology Assessment (HTA) bodies in different countries were also screened for relevant models. For each of the identified original models, details of the structure, data in- and outputs were extracted and the overall quality of the model in terms of the combination of structure, assumptions and data inputs were appraised using published criteria. Results: Seventy-eight articles and 41 HTAs reporting relevant economic evaluations were identified. There were ten models with multiple publications, and a further ten models with one associated publication. The critical review demonstrated that most had the same fundamental structure, used similar micro-simulation techniques and were based on the same key data sources. However, the process for identification of relevant data and their synthesis, and the selection of outcomes lacked transparency. The models differed according to the extent and type of interventions they evaluated and which diabetes complications and treatment-related adverse events were captured. For example, just one model incorporated changes in patient weight, despite the fact that weight gain can be a side-effect of some treatments, and weight loss a potential benefit of others. Conclusions: Whilst many economic models exist in T2D, most share common features such as the model type. Identified shortcomings are lack of transparency in data identification and evidence synthesis as well as the selection of the modelled outcomes. Future models should aim to include all relevant treatment outcomes, whether these relate to effects on underlying diabetes and its complications or to short- or long-term side effects of treatment.
UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspective
Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study.

BACKGROUND The purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol (PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH). METHODS As part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/MS/MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (BrACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22-day study to confirm the absence of drinking during a 7-day period before and the 14-day period after EtOH consumption. RESULTS (i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in BrAC and combined PEth levels of all participants; (ii) the areas under the curve (AUCs) for each participant's BrAC levels during the 6-hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half-life of combined PEth, determined during the 14-day period after EtOH consumption, was 4.6 ± 3.5 (SD) days (range: 1.0 to 13.1 days). CONCLUSIONS Combined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking.
Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction

Objective To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. Design We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe−/−) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed. Results ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe−/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation. Conclusions We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.
IPC-driven energy reduction for low-power design

Energy consumption is one of the most important design constraints for modern microprocessors, and designers have proposed many energy-saving techniques. This paper describes an interval-based identification and prediction mechanism for microprocessors energy reduction. Our mechanism employs a statistical sampling method during current interval run to identify its performance activity level in term of IPC (instruction per cycle) values and predict the future interval that could make contributions to processor runtime energy reduction by dynamically scaling the microprocessor voltage and frequency accordingly. In simulation, our approach achieves energy savings by an average of 29% with minor performance degradation, compared to a processor running at a fixed voltage and speed
A field programmable neural array

An analog circuit capable of accurately emulating large complex cells, or multiple less complex ones is described. This circuit is termed the FPNA or the field programmable neural array. It is analogous to the more familiar FPGA, but is composed of biologically relevant circuit components including active channels, dendrites, and synapses. Taking each of these circuit models, and adding a routing structure capable of routing outputs from cells (or external inputs) to any individual synapse at any node yields a device which is capable of emulating complex biological circuits. This circuit opens doors to investigating what particular types of computation individual cells are performing, as well as small networks simpler cells
Vedolizumab safety in pregnancy and newborn outcomes

We read with interest the study by Colombel et al 1 on vedolizumab (VDZ) safety in Crohn's disease (CD) and ulcerative colitis (UC). These data were derived from pivotal clinical trials which naturally exclude pregnant women, leaving this important area of pharmacovigilance unaddressed. Epidemiologically, the first age peak of IBD frequently overlaps with family planning. Thus, there is considerable interest among couples and healthcare providers on how VDZ impacts on pregnant women and newborns. Here we report the first four fully VDZ exposed and documented pregnancies and newborns. VDZ (MLN0002, MLN02, LDP-02, anti-α4β7) is a humanised monoclonal IgG1 antibody targeting α4β7 integrin. IgG1 is the predominant means of fetal immunity and maternal–fetal transport across the placenta, which increases linearly throughout pregnancy.2 Therefore, it can …
CRISPR/Cas9: at the cutting edge of hepatology

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome engineering has revolutionised biomedical science and we are standing on the cusp of medical transformation. The therapeutic potential of this technology is tremendous, however, its translation to the clinic will be challenging. In this article, we review recent progress using this genome editing technology and explore its potential uses in studying and treating diseases of the liver. We discuss the development of new research tools and animal models as well as potential clinical applications, strategies and challenges.
Controlled release systems for insulin delivery

Diabetes mellitus is a major cause of mortality in industrialised countries, and insulin has remained indispensable in the treatment of diabetes mellitus since its discovery. Generally, patients with diabetes mellitus need a relatively constant basal insulin supply to mimic a near-normal physiological pattern of insulin secretion. However, as a consequence of very short in vivo half-lifes, poor oral bioavailability and current lack of alternative delivery routes, insulin requires single or multiple daily subcutaneous injections to achieve the desired therapeutic effect, which is inconvenient and painful and with poor patient compliance. Therefore, there is a need for insulin delivery systems that have the capability of releasing the loaded insulin at a controlled and sustained rate for a prolonged period. This review examines recent (2000 – 2004) patents on the controlled release systems for insulin delivery, including those for injectable, oral, pulmonary and transdermal delivery, and the glucose-responsive controlled-release systems.
A 1.8V, 60dB/spl Omega/ 11 GHz transimpedance amplifier with strong immunity to input parasitic capacitance

A wideband differential transimpedance amplifier of an optical receiver is realized in a 0.18mum standard CMOS technology for the applications of Gigabit Ethernet data communication. The amplifier incorporates the regulated cascode (RGC) configuration to achieve strong immunity to large input parasitic capacitance and also exploits shunt inductive peaking technique to extend the bandwidth. Consequently, the RGC TIA has negligible effect on bandwidth from the large variation of photodiode capacitance. HSPICE simulations demonstrate the transimpedance gain of 60dBOmega, the -3dB bandwidth of 11GHz for 0.25pF photodiode capacitance, the average noise current spectral density of 18 pA/radicHz which corresponds to -14.4dBm optical sensitivity for 0.5A/W responsivity and 9dB extinction ration, and the DC power dissipation of 22mW from a single 1.8V supply
Limited Excessive Voluntary Alcohol Drinking Leads to Liver Dysfunction in Mice

BACKGROUND Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol. METHODS We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption. We measured a number of markers associated with early- and later-stage liver disruption, including liver steatosis, measures of liver cytochrome P4502E1 (CYP2E1) and alcohol dehydrogenase (ADH), alcohol metabolism, expression of cytokine mRNA, accumulation of 4-hydroxynonenal (4-HNE) as an indicator of oxidative stress, and alanine transaminase/aspartate transaminase as a measure of hepatocyte injury. RESULTS Importantly, repeated binge-like alcohol drinking increased triglyceride levels in the liver and plasma, and increased lipid droplets in the liver, indicators of steatosis. In contrast, a single binge-intake session or repeated moderate alcohol consumption did not alter triglyceride levels. In addition, alcohol exposure can increase rates of alcohol metabolism through CYP2E1 and ADH, which can potentially increase oxidative stress and liver dysfunction. Intermittent, excessive alcohol intake increased liver CYP2E1 mRNA, protein, and activity, as well as ADH mRNA and activity. Furthermore, repeated, binge-like drinking, but not a single binge or moderate drinking, increased alcohol metabolism. Finally, repeated, excessive intake transiently elevated mRNA for the proinflammatory cytokine IL-1B and 4-HNE levels, but did not alter markers of later-stage liver hepatocyte injury. CONCLUSIONS Together, we provide data suggesting that even relatively limited binge-like alcohol drinking can lead to disruptions in liver function, which might facilitate the transition to more severe forms of liver damage.
A multicenter, randomized, parallel-group, clinical trial comparing the safety and efficacy of loteprednol etabonate 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of Chinese patients with blepharokeratoconjunctivitis

Abstract Objective: To compare the efficacy and safety of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T) and dexamethasone 0.1%/tobramycin 0.3% (DM/T) ophthalmic suspensions in a Chinese population with ocular inflammation associated with blepharokeratoconjunctivitis (BKC). Research design and methods: This study was a multicenter, randomized, investigator-masked, parallel-group clinical trial. Patients aged ≥18 years with a clinical diagnosis of BKC in at least one eye received LE/T or DM/T administered 4 times daily for 2 weeks. At baseline and on days 3, 8, and 15 (visits 2, 3, and 4), clinical assessments of ocular signs and symptoms, visual acuity (VA), biomicroscopy, and intraocular pressure (IOP) were performed in both eyes. Main outcome measures: The primary efficacy endpoint was the change from baseline (CFB) to visit 4 in the signs and symptoms composite score in designated study eyes using a non-inferiority metric to compare LE/T to DM/T. Safety evaluation included adverse events, biomicroscopy findings, and changes in VA and IOP. Clinical trial registration: NCT number, NCT01028027. Results: A total of 308 patients were included in the per protocol population (n = 156 LE/T, n = 152 DM/T). A significant CFB in composite signs and symptoms was seen with both treatments at each follow-up visit (p < 0.0001). The mean (SD) CFB at visit 4 was −11.63 (4.56) and −12.41 (4.71) in the LE/T and DM/T groups, respectively, and the upper bound of the 90% confidence interval for the difference was less than the prespecified non-inferiority margin. Comparable results were found for secondary efficacy outcomes. Patients treated with DM/T experienced a significantly greater increase in mean CFB in IOP compared to those treated with LE/T at all follow-up visits (p ≤ 0.0186) and nearly twice as many IOP elevations ≥5 mmHg (p = 0.0020). Conclusion: Treatment with LE/T was at least as effective as DM/T in Chinese patients with BKC and had a better safety profile with respect to change in IOP.
Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS)

This document represents the first position statement produced by the British Society of Gastroenterology and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, setting out the minimum expected standards in diagnostic upper gastrointestinal endoscopy. The need for this statement has arisen from the recognition that while technical competence can be rapidly acquired, in practice the performance of a high-quality examination is variable, with an unacceptably high rate of failure to diagnose cancer at endoscopy. The importance of detecting early neoplasia has taken on greater significance in this era of minimally invasive, organ-preserving endoscopic therapy. In this position statement we describe 38 recommendations to improve diagnostic endoscopy quality. Our goal is to emphasise practices that encourage mucosal inspection and lesion recognition, with the aim of optimising the early diagnosis of upper gastrointestinal disease and improving patient outcomes.
Linear probability feedback processes

The analysis of discrete-time two-valued processes is often addressed assuming they have at most the memory of one step in the past. We here relax this assumption and propose a generator of antipodal stochastic processes which relies on a linear probability feedback that implies a memory equal to that of the feedback Alter. For such a scheme an explicit spectrum formula is derived as well as a synthesis procedure going from a special type of spectrum specification to feedback filter design.