Miracle-dz/UniFAR-FTUs huggingface dataset:
A 1-V, 10-bit rail-to-rail successive approximation analog-to-digital converter in standard 0.18 /spl mu/m CMOS technology

Two architectures for a 1-V, 10-bit 200-kS/s successive approximation analog-to-digital converter (ADC) implemented in a standard CMOS 0.18 /spl mu/m digital process are presented. A track-and-hold circuit based on a novel implementation of the bootstrapped low-voltage analog CMOS switch with a novel rail-to-rail track-and-latch comparator circuit is described. A pMOS-only ladder containing a rail-to-rail current-to-voltage converter, performs the DAC function in the second ADC topology whereas a conventional R-2R ladder is used in the first one. Successive approximation and control logic is implemented using of robust single clock phase D flip flop.
The UN in the lab

We consider two alternatives to inaction for governments combating terrorism, which we term Defense and Prevention. Defense consists of investing in resources that reduce the impact of an attack, and generates a negative externality to other governments, making their countries a more attractive objective for terrorists. In contrast, Prevention, which consists of investing in resources that reduce the ability of the terrorist organization to mount an attack, creates a positive externality by reducing the overall threat of terrorism for all. This interaction is captured using a simple $$3\times 3$$3×3 “Nested Prisoner’s Dilemma” game, with a single Nash equilibrium where both countries choose Defense. Due to the structure of this interaction, countries can benefit from coordination of policy choices, and international institutions (such as the UN) can be utilized to facilitate coordination by implementing agreements to share the burden of Prevention. We introduce an institution that implements a burden-sharing policy for Prevention, and investigate experimentally whether subjects coordinate on a cooperative strategy more frequently under different levels of cost sharing. In all treatments, burden sharing leaves the Prisoner’s Dilemma structure and Nash equilibrium of the game unchanged. We compare three levels of burden sharing to a baseline in a between-subjects design, and find that burden sharing generates a non-linear effect on the choice of the efficient Prevention strategy and overall performance. Only an institution supporting a high level of mandatory burden sharing generates a significant improvement in the use of the Prevention strategy.
Interplay of pathogenic forms of human tau with different autophagic pathways

Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule‐stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients’ brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone‐mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age‐related disease. We have found that the pathogenic P301L mutation inhibits degradation of tau by any of the three autophagic pathways, whereas the risk‐associated tau mutation A152T reroutes tau for degradation through a different autophagy pathway. We also found defective autophagic degradation of tau when using mutations that mimic common posttranslational modifications in tau or known to promote its aggregation. Interestingly, although most mutations markedly reduced degradation of tau through autophagy, the step of this process preferentially affected varies depending on the type of tau mutation. Overall, our studies unveil a complex interplay between the multiple modifications of tau and selective forms of autophagy that may determine its physiological degradation and its faulty clearance in the disease context.
Risk factors for post-ERCP pancreatitis: a prospective multicenter study in upper Egypt

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) has become widely available for diagnosis and treatment of pancreatic and biliary diseases. Pancreatitis is the most common and serious complication to occur after ERCP resulting in substantial morbidity and occasional mortality. The aim of this study was to evaluate the potential patient and procedure-related risk factors for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in a prospective multicenter study. Patients and methods Consecutive ERCP procedures were prospectively studied at five centers (two universities, three private). Data were collected on patient characteristics and endoscopic techniques before the procedure, at the time of procedure, and 24-72 h after discharge. PEP was diagnosed and its severity graded according to consensus criteria. Results Pancreatitis occurred after 104 (8.9%) of 1162 consecutive ERCP procedures and was graded mild in 66 (63.5%), moderate in 30 (28.8%), and severe in eight (7.7%) cases. On univariate analysis, 11 of 18 evaluated variables were found to be significantly associated with PEP. On multivariate analysis, significant risk factors with adjusted odds ratio (OR) were: difficult cannulation (OR: 10.2), previous PEP (OR: 8.1), previous pancreatitis (OR: 7.9), at least two pancreatic duct injections (OR: 3.1), pancreatic duct cannulation (OR: 2.7), difficult stone extraction (OR: 2.2), and precut sphincterotomy (OR: 1.2). Conclusion Technique-related risk factors are probably more numerous and potent than patient-related ones in determining high-risk predictors for PEP.
Mast cells: bridging the gap between pre- and post-capillary pulmonary hypertension?

According to the current guidelines for the diagnosis and treatment of pulmonary hypertension (PH) [1, 2], the Dana Point diagnostic classification separates pre-capillary PH, i.e. PH due to pulmonary vascular disease mainly affecting the pre-capillary arteriolar compartment ( i.e. Dana Point groups 1, 3, 4 and 5), from post-capillary disease that originates distal to the capillaries and involves morphological changes in the pre-capillary compartment only occur after a significant pressure increase in the venous compartment ( i.e. Dana Point group 2). Currently, a single haemodynamic parameter, i.e. wedge pressure [3], that is commonly flawed by methodological errors [4] is employed to distinguish between pre- and post-capillary disease. This distinction is vital because treatment is completely different for the two classes of disease [2], with a virtual “therapeutic gap” between the two disorders. For example, epoprostenol, the life-saving treatment for pulmonary arterial hypertension (PAH) [5], was shown to be detrimental in congestive heart failure [6]. PH with left-sided heart disease is classified as a non-PAH form that includes all conditions associated with increased left ventricular filling pressure. A transpulmonary gradient (mean pulmonary arterial pressure ( P pa)−pulmonary capillary wedge pressure ( P pcw)) >12 mmHg has been arbitrarily declared as the haemodynamic threshold indicating significant pre-capillary pulmonary vascular disease in left-sided heart disease, and has been classified as “reactive” or “out-of-proportion” PH. By contrast, transpulmonary gradients ≤12 mmHg have been classified as passive PH, i.e. PH due to hydrostatic pressure transmitted across the capillary bed of the lung, implying a lack of significant anatomical changes of the pre-capillary vessels. Naturally, these pressures can be directly changed by relieving left-sided pressures, for example by diuretic …
Investing in the mental health of Fife: a sustainable model for increasing mental health workforce capacity to help children flourish

Playfield Institute is a unique partnership between child and adolescent mental health services (CAMHS) and public health. The institute model is an innovative response to the national challenge to mainstream mental health. Its focus is to build the capacity of frontline workers (otherwise known as the children's workforce eg. school nurses, social workers, teachers, foster carers etc.) to promote the mental health of children and young people. It works by providing a multi‐agency forum for sharing information and developing practical skills on how to help children flourish. It also encourages reflection on practice and undertakes research that has a direct impact on the development of training and practice. To date, the Institute has achieved the following main outcomes: the facilitation of a successful training programme, the development of a well used, effective, online resource and the co‐ordination of a range of applied research projects. This paper discusses why the Institute was set up, what it is, what it has achieved and how the model is sustainable.
α-Haemolysin of Escherichia coli in IBD: a potentiator of inflammatory activity in the colon

Objective α-Haemolysin (HlyA) influences host cell ionic homeostasis and causes concentration-dependent cell lysis. As a consequence, HlyA-producing Escherichia coli is capable of inducing ‘focal leaks’ in colon epithelia, through which bacteria and antigens translocate. This study addressed the role of HlyA as a virulence factor in the pathogenesis of colitis according to the ‘leaky gut’ concept. Design To study the action of HlyA in the colon, we performed oral administration of HlyA-expressing E coli-536 and its isogenic α-haemolysin-deficient mutant (HDM) in three mouse models: wild type, interleukin-10 knockout mice (IL-10−/−) and monoassociated mice. Electrophysiological properties of the colonised colon were characterised in Ussing experiments. Inflammation scores were evaluated and focal leaks in the colon were assessed by confocal laser-scanning microscopy. HlyA quantity in human colon biopsies was measured by quantitative PCR. Results All three experimental mouse models infected with HlyA-producing E coli-536 showed an increase in focal leak area compared with HDM. This was associated with a decrease in transepithelial electrical resistance and an increase in macromolecule uptake. As a consequence, inflammatory activity index was increased to a higher degree in inflammation-prone mice. Mucosal samples from human colon were E coli HlyA-positive in 19 of 22 patients with ulcerative colitis, 9 of 9 patients with Crohn's disease and 9 of 12 healthy controls. Moreover, focal leaks were found together with 10-fold increased levels of HlyA in active ulcerative colitis. Conclusions E coli HlyA impairs intestinal barrier function via focal leak induction in the epithelium, thereby intensifying antigen uptake and triggering intestinal inflammation in vulnerable mouse models. Therefore, HlyA-expressing E coli strains should be considered as potential cofactors in the pathogenesis of intestinal inflammation.
Anxiety, relaxation and anaesthesia for day‐case surgery

It is recognized that pre-operative anxiety can have adverse effects on the course and outcome of surgery and there is a considerable amount of research into the influences of interventions for pre-operative anxiety on a number of post-operative variables. However, little attention has been paid to the potential influences of treatments on intra-operative variables, most notably on the facilitation of anaesthesia. The present study examined the impact of a brief relaxation procedure on anaesthesia in comparison to attention-control and no-treatment control procedures. A sample of 21 patients about to undergo anaesthesia for day-case surgery were randomly assigned to one of the three conditions. It was found that the relaxation treatment significantly reduced pre-operative anxiety as measured by the state scale of the State-Trait Anxiety Inventory (Spielberger, 1983). This reduction was reflected in physiological indicators of anxiety. Both the relaxation group and the attention-control group required significantly less time to induce anaesthesia and less of the anaesthetic agent used to maintain anaesthesia. The relaxation group also scored significantly lower than the no-treatment control group on an anaesthetist's rating of difficulty of maintenance of anaesthesia. Whilst the relaxation treatment appeared to have no advantages over the attention-control procedure in terms of anaesthetic requirements, the latter treatment did not reduce anxiety and showed no benefit over the no-treatment control condition in terms of an anaesthetist's rating of difficulty of maintenance of anaesthesia. In addition, following recovery the relaxation subjects reported more favourable perceptions of their treatment than the attention-control subjects.
IBS with intestinal microbial dysbiosis: a new and clinically relevant subgroup?

Symptoms compatible with IBS, that is, abdominal pain and discomfort, bloating, abdominal distention and an erratic bowel function, are very common reasons for GI consultations in primary care1 and patients with IBS are one of the most frequent patient categories in gastroenterology outpatient clinics.2 Despite being very common and in spite of considerable research effort during the last decades, the pathophysiology of IBS is still considered to be complex and incompletely understood3 ,4 and even though our understanding of this disabling condition arguably has increased tremendously, we still cannot use knowledge from pathophysiology studies to subgroup IBS patients in a clinically meaningful way. In everyday clinical work, we still rely on subgrouping patients based on the predominant bowel habit when we decide how to manage and treat the patients.5 Even though we have new pharmacological treatment options targeting specific molecules in the GI tract,6–9 only a subset of patients will respond favourably when we choose patients based on the current imperfect system to subgroup patients, that is, into patients with predominant diarrhoea, constipation or mixed bowel habit.5 Ideally, clinical subgrouping based on the underlying pathophysiology should have the potential to lead to targeted …
Impaired pulmonary function and the risk of tuberculosis: a population-based cohort study

To the Editors: It is well known that pulmonary tuberculosis (TB) can cause lung impairment leading to chronic obstructive pulmonary disease (COPD) 1, but less is known to what extent impaired lung function increases the risk of TB. A case–control study from the UK found patients with emphysema to have a three-fold increased risk of TB, adjusted for smoking and the use of corticosteroids 2. A cohort study from Denmark found moderate-to-severe COPD to be associated with a two- to three-fold increased risk of hospitalisation with TB 3. We have previously shown that patients hospitalised with COPD have a three-fold increased risk of active TB compared with population controls 4. In the present study, we examine the risk of active TB in relation to lung function in a cohort who underwent spirometry in 1974–1992. Between 1974 and 1992, 22,444 males and 10,902 females, born 1921–1949, participated in a health screening programme, the Malmo Preventive Project. Complete birth cohorts, born in pre-specified years, from the city of Malmo were invited; the overall participation proportion was ∼70% 5. The screening included physical examination, spirometry, blood samples and assessment of lifestyle factors by means of a self-administered questionnaire. Some questions varied between the cohorts. We excluded 4,413 individuals because of missing spirometry data; 26 individuals were excluded because of missing data on either body mass index (BMI), smoking or immigration status, leaving a total of 28,907 individuals in final analysis (21,174 males and 7,733 females). BMI as was calculated as mass/height2 (in kg·m−2). Individuals were regarded as having diabetes mellitus if they answered positively to the question “Do you have diabetes mellitus? ” or their fasting blood glucose level was ≥6.1 mmol·L−1. Around 96% of the cohort (n = 27,789) answered questions on alcohol. Individuals …
XIAP variants in male Crohn's disease

Objective The genetic basis of inflammatory bowel disease (IBD) is incompletely understood. The aim of this study was to identify rare genetic variants involved in the pathogenesis of IBD. Design Exome sequencing and immunological profiling were performed in a patient with early onset Crohn's disease (CD). The coding region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was sequenced in samples of 275 paediatric IBD and 1047 adult-onset CD patients. XIAP genotyping was performed in samples of 2680 IBD patients and 2864 healthy controls. Functional effects of the variants identified were investigated in primary cells and cultured cell lines. Results Our results demonstrate the frequent occurrence of private variants in XIAP in about four percent of male patients with paediatric-onset CD. While XIAP mutations are known to be associated with the primary immunodeficiency (PID) X-linked lymphoproliferative disease type 2 (XLP2), CD patients described here exhibited intestinal inflammation in the absence of XLP2 and harboured a spectrum of mutations partially distinct from that observed in XLP2. The majority of XIAP variants identified was associated with a selective defect in NOD1/2 signalling, impaired NOD1/2-mediated activation of NF-κB, and altered NF-κB-dependent cytokine production. Conclusions This study reveals the unanticipated, frequent occurrence of XIAP variants in male paediatric-onset CD. The link between XIAP and NOD1/2, and the association of XIAP variants with XLP2, support the concept of PID in a subset of IBD patients. Moreover, these studies provide a rationale for the implementation of XIAP sequencing in clinical diagnostics in male patients with severe CD.
The Pathogenesis of Idiopathic Pulmonary Fibrosis Focusing on Epithelial Cells

Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition and scar tissue formation in the interstitial lungs over time. The epidemiology of IPF is 13 to 20 cases per 100,000 people [1]. Typically the disease is found in people between the ages of 50 and 70 and affects men more frequently than women. There are no proven risk factors for IPF, but a minority of patients has a family history of lung scarring. The clinical presentation includes exertional dyspnea, cough, functional and exercise limitation, impaired quality of life and risk for acute respiratory failure and death. The median survival time is 3-5 years. Unfortunately, there is no FDA approved treatment or cure for IPF and it is ultimately fatal. The accumulation of activated myofibroblastsis thought to be the source of interstitial collagens, but the cellular origin of activated fibroblasts and their particular contribution to the deposition of extracellular matrix remains unknown. There are three proposed cellular origins of myofibroblasts including expansion of lung residential fibroblasts, recruitment of bone marrow-derived fibrocytes, and epithelial-mesenchymal transition (EMT) [2]. EMT is defined as Alveolar Epithelial Cells (AECs) that undergo transition into migratory and/or invasive mesenchymal cells. Recent studies show that regulation of EMT involves many transcription factors like Twist, Snail, and Foxm1 to activate mesenchymal protein expression [3-5]. Previous studies suggest that up to a third of fibroblasts in the lung following bleomycin injury are derived from EMT; however the extent to which these EMT-derived fibroblasts contribute to the deposition of fibrillar collagen is unclear [6,7]. This discussion will focus on the contribution of AECs to the pathophysiology of pulmonary fibrosis. Understanding this critical step will facilitate future drug discovery to block or reverse fibrosis development. A complete review of IPF can be found in other places [8,9].
A Randomized Control Trial of the Application of Efficacy Training to Balance Assessment

Reduced balance confidence often translates into a fear of falling, which reinforces a sedentary lifestyle. Purpose: A self-efficacy intervention was assessed for improvements in balance confidence and performance when compared with controls. Methods: Thirty-five assisted-living residents were randomly assigned to an exercise-only or exercises and efficacy-training groups two times every week for four weeks. Results: Activities of Balance Confidence Scale (ABC) using ANCOVA demonstrated no significant differences (F = 0.005, p = 0.944) in balance confidence. Balance performance however, as measured by the Berg Balance Scale using ANCOVA was significantly improved (F = 33.453, p = 0.0001). Conclusion: This intervention produced significant changes in balance performance without demonstrating significant changes in confidence measurement. Continued assessments and intervention trials such as this will demonstrate scientific evidence needed to promote optimal functioning in older adults.
A multirate approach to multichannel blind deconvolution

Multichannel blind deconvolution techniques can be used to de-reverberate and separate audio signals recorded by arrays of microphones in multimedia applications. Experimental results are available only for simple cases, using synthetic signals or considering short and stationary impulse responses. The problem of multichannel blind deconvolution of real-world audio signals is considered, using true speech signals recorded in a real furnished room. The obtained results are very good in terms of both separation and de-reverberation, demonstrating that the problem can be effectively challenged in practice. Since the complexity of the system can easily exceed the single DSP processor capabilities, a new sub-band architecture is proposed, which shows some structural and practical advantages, especially when processor arrays are employed.
Systemic manifestations and comorbidities of COPD

Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the “spill-over” of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.