Sacral nerve modulation for patients with fecal incontinence: long-term outcome and effects on sexual function

Double incontinence; Sacral nerve modulation; Urinary incontinenceDoble incontinencia; Modulación del nervio sacro; Incontinencia urinariaDoble incontinència; Modulació del nervi sacre; Incontinència urinàriaSacral nerve modulation has become an established treatment for fecal and urinary incontinence, and sexual disorders. The objective of this study was to evaluate the long-term outcome of sacral neuromodulation in patients with fecal or combined fecal and urinary incontinence (double incontinence), assessing its safety, efficacy, and impact on quality of life and sexual function. This was a multicentric, retrospective, cohort study including patients with fecal or double incontinence who received sacral neuromodulation at seven European centers between 2007 and 2017 and completed a 5-year follow-up. The main outcome measures included improvements of incontinence symptoms and quality of life compared with baseline, evaluated using validated tools and questionnaires at 1-, 6-, 12-, 36- and 60-month follow-up. 108 (102 women, mean age 62.4 ± 13.4 years) patients were recruited, of whom 88 (81.4%) underwent definitive implantation of the pacemaker. Patients’ baseline median Cleveland Clinic Incontinence Score was 15 (10–18); it decreased to 2 (1–4) and 1 (1–2) at the 12- and 36-month follow-up (p < 0.0001), remaining stable at the 5-year follow-up. Fecal incontinence quality of life score improved significantly. All patients with sexual dysfunction (n = 48) at baseline reported symptom resolution at the 5-year follow-up. The study was limited by the retrospective design and the relatively small patient sample. Sacral nerve modulation is an effective treatment for fecal and double incontinence, achieving satisfactory long-term success rates, with resolution of concomitant sexual dysfunction.Open access funding provided by Università degli Studi della Campania Luigi Vanvitelli within the CRUI-CARE Agreement. This research was not funded by any agency in the public, commercial, or not-for-profit sectors

Search and design of nonmagnetic centrosymmetric layered crystals with large local spin polarization

Until recently, spin polarization in nonmagnetic materials was the exclusive territory of noncentrosymmetric structures. It was recently shown that a form of &quot;hidden spin polarization&quot; (named the &quot;Rashba-2&quot; or &quot;R-2&quot; effect) could exist in globally centrosymmetric crystals provided the individual layers belong to polar point group symmetries. This realization could considerably broaden the range of materials that might be considered for spin-polarization spintronic applications to include the hitherto &quot;forbidden spintronic compound&quot; that belongs to centrosymmetric symmetries. Here we take the necessary steps to transition from such general, material-agnostic condensed matter theory arguments to material-specific &quot;design principles&quot; that could aid future laboratory search of R-2 materials. Specifically, we (i) classify different prototype layered structures that have been broadly studied in the literature in terms of their expected R-2 behavior, including the Bi2Se3-structure type (a prototype topological insulator), MoS2-structure type (a prototype valleytronic compound), and LaBiOS2-structure type (a host of superconductivity upon doping); (ii) formulate the properties that ideal R-2 compounds should have in terms of combination of their global unit cell symmetries with specific point group symmetries of their constituent &quot;sectors&quot;; and (iii) use first-principles band theory to search for compounds from the prototype family of LaOBiS2-type structures that satisfy these R-2 design metrics. We initially consider both stable and hypothetical M???OMX2 (M&apos;: Sc, Y, La, Ce, Pr, Nd, Al, Ga, In, Tl; M: P, As, Sb, Bi; X: S, Se, Te) compounds to establish an understanding of trends of R-2 with composition, and then indicate the predictions that are expected to be stable and synthesizable. We predict large spin splittings (up to ???200meV for holes in LaOBiTe2) as well as surface Rashba states. Experimental testing of such predictions is called for. &amp;copy; 2015 American Physical Society.open0

Spin Calogero Particles and Bispectral Solutions of the Matrix KP Hierarchy

Pairs of $n\times n$ matrices whose commutator differ from the identity by a matrix of rank $r$ are used to construct bispectral differential operators with $r\times r$ matrix coefficients satisfying the Lax equations of the Matrix KP hierarchy. Moreover, the bispectral involution on these operators has dynamical significance for the spin Calogero particles system whose phase space such pairs represent. In the case $r=1$, this reproduces well-known results of Wilson and others from the 1990's relating (spinless) Calogero-Moser systems to the bispectrality of (scalar) differential operators. This new class of pairs $(L, \Lambda)$ of bispectral matrix differential operators is different than those previously studied in that $L$ acts from the left, but $\Lambda$ from the right on a common $r\times r$ eigenmatrix.Comment: 16 page

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.&lt;/p&gt

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Radiation combined with macrophage depletion promotes adaptive immunity and potentiates checkpoint blockade

Emerging evidence suggests a role for radiation in eliciting anti-tumour immunity. We aimed to investigate the role of macrophages in modulating the immune response to radiation. Irradiation to murine tumours generated from colorectal (MC38) and pancreatic (KPC) cell lines induced colony-stimulating factor 1 (CSF-1). Coincident with the elevation in CSF-1, macrophages increased in tumours, peaking 5 days following irradiation. These tumour-associated macrophages (TAMs) were skewed towards an immunosuppressive phenotype. Macrophage depletion via anti-CSF (aCSF) reduced macrophage numbers, yet only achieved tumour growth delay when combined with radiation. The tumour growth delay from aCSF after radiation was abrogated by depletion of CD8 T cells. There was enhanced recognition of tumour cell antigens by T cells isolated from irradiated tumours, consistent with increased antigen priming. The addition of anti-PD-L1 (aPD-L1) resulted in improved tumour suppression and even regression in some tumours. In summary, we show that adaptive immunity induced by radiation is limited by the recruitment of highly immunosuppressive macrophages. Macrophage depletion partly reduced immunosuppression, but additional treatment with anti-PD-L1 was required to achieve tumour regression

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p &#60; 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

The DEEP Groth Strip Survey. I. The Sample

The Deep Extragalactic Exploratory Probe (DEEP) is a multi-phase research program dedicated to the study of the formation and evolution of galaxies and of large scale structure in the distant Universe. This paper describes the first five-year phase, denoted DEEP1. A series of ten DEEP1 papers will discuss a range of scientific topics (e.g., the study of photometric and spectral properties of a general distant galaxy survey, the evolution observed in galaxy populations of varied morphologies). The observational basis for these studies is the Groth Survey Strip field, a 127 square arcminute region which has been observed with the Hubble Space Telescope in both broad I-band and V-band optical filters and with the Low Resolution Imaging Spectrograph on the Keck Telescopes. Catalogs of photometric and structural parameters have been constructed for 11,547 galaxies and stars at magnitudes brighter than 29, and spectroscopy has been conducted for a magnitude-color weighted subsample of 818 objects. We evaluate three independent techniques for constructing an imaging catalog for the field from the HST data, and discuss the depth and sampling of the resultant catalogs. The selection of the spectroscopic subsample is discussed, and we describe the multifaceted approach taken to prioritizing objects of interest for a variety of scientific subprograms. A series of Monte Carlo simulations then demonstrates that the spectroscopic subsample can be adequately modeled as a simple function of magnitude and color cuts in the imaging catalog.Comment: ApJS accepted, 15 pages, 12 figures. Version with higher-quality figures available at http://astronomy.nmsu.edu/nicol

Albuminuria Testing in Hypertension and Diabetes:An Individual-Participant Data Meta-Analysis in a Global Consortium

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%-74.5%) in diabetes and 4.1% (1.3%-20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42-1.60]; in hypertension, 1.36 [1.28-1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR/g, the median 5-year incidence of ACR ≥30 mg/g across cohorts was 23.9% in diabetes and 21.7% in hypertension. Incident albuminuria was associated with initiation of renin-angiotensin-aldosterone system inhibitors (incidence-rate ratio [95% CI], diabetes 3.09 [2.71-3.53]; hypertension 2.87 [2.29-3.59]). In conclusion, despite similar risk of albuminuria to those with diabetes, ACR screening in patients with hypertension was low. Our findings suggest that regular albuminuria screening should be emphasized to enable early detection of chronic kidney disease and initiation of treatment with cardiovascular and renal benefits