Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Stability, Structure and Scale: Improvements in Multi-modal Vessel Extraction for SEEG Trajectory Planning

Purpose Brain vessels are among the most critical landmarks that need to be assessed for mitigating surgical risks in stereo-electroencephalography (SEEG) implantation. Intracranial haemorrhage is the most common complication associated with implantation, carrying signi cant associated morbidity. SEEG planning is done pre-operatively to identify avascular trajectories for the electrodes. In current practice, neurosurgeons have no assistance in the planning of electrode trajectories. There is great interest in developing computer assisted planning systems that can optimise the safety pro le of electrode trajectories, maximising the distance to critical structures. This paper presents a method that integrates the concepts of scale, neighbourhood structure and feature stability with the aim of improving robustness and accuracy of vessel extraction within a SEEG planning system. Methods The developed method accounts for scale and vicinity of a voxel by formulating the problem within a multi-scale tensor voting framework. Feature stability is achieved through a similarity measure that evaluates the multi-modal consistency in vesselness responses. The proposed measurement allows the combination of multiple images modalities into a single image that is used within the planning system to visualise critical vessels. Results Twelve paired datasets from two image modalities available within the planning system were used for evaluation. The mean Dice similarity coe cient was 0.89 ± 0.04, representing a statistically signi cantly improvement when compared to a semi-automated single human rater, single-modality segmentation protocol used in clinical practice (0.80 ±0.03). Conclusions Multi-modal vessel extraction is superior to semi-automated single-modality segmentation, indicating the possibility of safer SEEG planning, with reduced patient morbidity

Design Patterns for Efficient Solutions to NP-Complete Problems in Membrane Computing

Many variants of P systems have the ability to generate an exponential number of membranes in linear time. This feature has been exploited to elaborate (theoretical) efficient solutions to NP-complete, or even harder, problems. A thorough review of the existent solutions shows the utilization of common techniques and procedures. The abstraction of the latter into design patterns can serve to ease and accelerate the construction of efficient solutions to new hard problems.Ministerio de Economía y Competitividad TIN2017-89842-

Counting Membrane Systems

A decision problem is one that has a yes/no answer, while a counting problem asks how many possible solutions exist associated with each instance. Every decision problem X has associated a counting problem, denoted by #X, in a natural way by replacing the question “is there a solution?” with “how many solutions are there?”. Counting problems are very attractive from a computational complexity point of view: if X is an NP-complete problem then the counting version #X is NP-hard, but the counting version of some problems in class P can also be NP-hard. In this paper, a new class of membrane systems is presented in order to provide a natural framework to solve counting problems. The class is inspired by a special kind of non-deterministic Turing machines, called counting Turing machines, introduced by L. Valiant. A polynomial-time and uniform solution to the counting version of the SAT problem (a well-known #P-complete problem) is also provided, by using a family of counting polarizationless P systems with active membranes, without dissolution rules and division rules for non-elementary membranes but where only very restrictive cooperation (minimal cooperation and minimal production) in object evolution rules is allowed

Quality of life, tuberculosis and treatment outcome; a case-control and nested cohort study

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities 13/7/2016-24/2/2018 and followed-up until 8/11/2019. Inclusion criteria were: age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly-selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with: QOL; health; energy; activities of daily living (ADL); self; relationships; money; and living place. FINDINGS: Newly-diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13-points had 4.2-times (95%CI=2.3,7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later and for patients with successful treatment, QOL became similar to participants who never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psycho-socio-economic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL 8-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care

Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study

Aortic stiffness is associated with an increased risk of cardio- and cerebrovascular disease and mortality and may increase risk of dementia. The aim of the present study is to examine the association between arterial stiffness and cognitive decline in a large prospective cohort study with three repeated cognitive assessment over 7 years of follow-up. Aortic pulse wave velocity (PWV) was measured among 4300 participants (mean ± standard deviation age 65.1 ± 5.2 years) in 2007–2009 and categorized based on the tertiles: (lowest third:  8.91 m/s). A global cognitive score was calculated in 2007–2009, 2012–2013, and 2015–2016 based on responses to memory, reasoning and fluency tests. Standardized global cognitive score (mean = 0, SD = 1) in highest third versus lowest third of PWV category was lower at baseline (− 0.12, 95% CI − 0.18, − 0.06). Accelerated 7-year cognitive decline was observed among individuals with the highest PWV [difference in 7-year cognitive change for highest third versus lowest third PWV: − 0.06, 95% CI − 0.11, − 0.01, P < 0.01]. Higher aortic stiffness was associated with faster cognitive decline. Clinicians may be able to use arterial stiffness severity as an indicator to administer prompt treatments to prevent or delay the onset of cognitive decline or dementia. Future studies need to determine whether early intervention of vascular stiffness is effective in delaying these outcomes

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Association of anorexia nervosa with risk of cancer. A systematic review and meta-analysis

This is the final version. Available from the publisher via the DOI in this record.IMPORTANCE Anorexia nervosa is recognized as an important cause of morbidity in young people. However, the risk of cancer in people with anorexia nervosa remains uncertain. OBJECTIVE To evaluate the association of anorexia nervosa with the risk of developing or dying of cancer. DATA SOURCES MEDLINE, Scopus, Embase, and Web of Science from database inception to January 9, 2019. STUDY SELECTION Published observational studies in humans examining the risk of cancer in people with anorexia nervosa compared with the general population or those without anorexia nervosa. Studies needed to report incidence or mortality rate ratios (RRs). DATA EXTRACTION AND SYNTHESIS Screening, data extraction, and methodological quality assessment were performed by at least 2 researchers independently. A random-effects model was used to synthesize individual studies. Heterogeneity (I 2 ) was assessed and 95% prediction intervals (PIs) were calculated. MAIN OUTCOMES AND MEASURES All cancer incidence and cancer mortality associated with anorexia nervosa. Secondary outcomes were site-specific cancer incidence and mortality. RESULTS Seven cohort studies published in 10 articles (42 602 participants with anorexia nervosa) were included. Anorexia nervosa was not associated with risk of developing any cancer (4 studies in women; RR, 0.97; 95% CI, 0.89-1.06; P = .53; I 2 , 0%; 95% PI, 0.80-1.18; moderate confidence). Anorexia nervosa was associated with decreased breast cancer incidence (5 studies in women; RR, 0.60; 95% CI, 0.50-0.80; P < .001; I 2 , 0%; 95% PI, 0.44-0.83; high confidence). Conversely, anorexia nervosa was associated with increased risk of developing lung cancer (3 studies in women; RR, 1.50; 95% CI, 1.06-2.12; P = .001; I 2 , 0%; 95% PI, 0.19-16.46; low confidence) and esophageal cancer (2 studies in women; RR, 6.10; 95% CI, 2.30-16.18; P < .001; I 2 , 0%; low confidence). CONCLUSIONS AND RELEVANCE Among people with anorexia nervosa, risk of developing cancer did not differ compared with the general population, but a significantly reduced risk of breast cancer was observed. Understanding the mechanisms underlying these associations could have important preventive potentialGeneralitat ValencianaCarlos III Health Institut

Does Poorer Pulmonary Function Accelerate Arterial Stiffening?

Whether poorer pulmonary function accelerates progression of arterial stiffness remains unknown as prior observational studies have not examined longitudinal changes in arterial stiffness in relation to earlier pulmonary function. Data (N=5342, 26% female) were drawn from the Whitehall II cohort study. Participants completed repeated assessments of forced expiratory volume in 1 second (FEV1, L) and carotid-femoral pulse wave velocity (cf-PWV, m/s) over 5 years. The effect of FEV1 on later cf-PWV and its progression was estimated using linear mixed-effects modeling. Possible explanatory mechanisms, such as mediation by low-grade systemic inflammation, common-cause explanation by preexisting cardiometabolic risk factors, and reverse-causation bias, were assessed. Poorer pulmonary function was associated with later higher cf-PWV and its subsequent progression (cf-PWV 5-year change 0.09, 95% CI 0.03-0.17 per SD lower FEV1) after adjustment for age, sex, ethnicity, heart rate, and mean arterial pressure. Decrease in pulmonary function was associated with later higher cf-PWV (0.17, 95% CI 0.04-0.30 in the top compared to bottom quartile of decline in FEV1). There was no evidence to support mediation by circulating CRP (C-reactive protein) or IL (interleukin)-6. Furthermore, arterial stiffness was not associated with later FEV1 after accounting for cardiometabolic status. In conclusion, poorer pulmonary function predicted future arterial stiffness. These findings support pulmonary function as a clinically important risk factor for arterial stiffness and provide justification for future intervention studies for pulmonary function based on its relationship with arterial stiffness

Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study

BACKGROUND: Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures. METHODS: In this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45-55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data. FINDINGS: Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model. INTERPRETATION: Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. FUNDING: British Heart Foundation and British Medical Research Council