Search

We have developed “Microscope-Cockpit” (Cockpit), a highly adaptable open source user-friendly Python-based Graphical User Interface (GUI) environment for precision control of both simple and elaborate bespoke microscope systems. The user environment allows next-generation near instantaneous navigation of the entire slide landscape for efficient selection of specimens of interest and automated acquisition without the use of eyepieces. Cockpit uses “Python-Microscope” (Microscope) for high-performance coordinated control of a wide range of hardware devices using open source software. Microscope also controls complex hardware devices such as deformable mirrors for aberration correction and spatial light modulators for structured illumination via abstracted device models. We demonstrate the advantages of the Cockpit platform using several bespoke microscopes, including a simple widefield system and a complex system with adaptive optics and structured illumination. A key strength of Cockpit is its use of Python, which means that any microscope built with Cockpit is ready for future customisation by simply adding new libraries, for example machine learning algorithms to enable automated microscopy decision making while imaging.

Introduction Recent studies in in vitro fertilisation (IVF) patients have associated abnormal vaginal microbiota (AVM) with poor clinical pregnancy rates of 6%–9% per embryo transfer. The biological plausibility for this finding is hypothesised to be ascending infection to the endometrium which in turn hampers embryo implantation. New molecular based diagnosis may offer advantages compared to microscopical diagnosis of AVM which has huge inter-study variability ranging from 4 to 38%; however, the important question is whether screening and treatment of AVM would improve reproductive outcomes in IVF patients. Herein, we describe a protocol for an ongoing double-blind, placebo-controlled multicentre trial of IVF patients diagnosed with AVM and randomised in three parallel groups 1:1:1.Methods and analysis This is a drug intervention study where IVF patients will be screened for AVM, using a qPCR assay targeting Atopobium vaginae and Gardnerella vaginalis. If positive, patients will be randomised to one of the three study arms. The first arm consists of clindamycin 300 mg ×2 daily for 7 days followed by vaginal Lactobacillus crispatus CTV-05 until clinical pregnancy scan week 7–9. The second arm consists of clindamycin and placebo L. crispatus CTV-05, whereas patients in the third arm will be treated with placebo/placebo. We used a superiority design to estimate that active treatment in both arms will increase the primary outcome, clinical pregnancy rate per embryo transfer, from 20% to 40%. A potential difference between the two active arms was considered exploratory. With a power of 80% and an alpha at 5%, the sample size is estimated to be 333 patients randomised. A pre-planned interim analysis is scheduled at 167 patients randomised.Ethics and dissemination All patients have to give informed consent. Dissemination of results is ensured in clinical trial agreements whether they be positive or not. Ethics committee, Central Denmark Region approved this protocol.Trial registration number ICH-GCP monitored trial, EudraCT 2016-002385-31; Pre-results.

Objective: A matched, case?control study was conducted to examine the association between development of low birth weight (LBW) and maternal factors, including dietary intake, comorbidities, and socioeconomic factors, among women in Cap Haitien, Haiti. Design: Mothers who delivered LBW babies; defined as ?2.5?kg, were identified by review of the medical record and matched to mothers of similar age, parity, with normal birth weight (NBW) babies. A survey was administered consisting of Women's Dietary Diversity Score (WDDS), maternal reporting of comorbidities, income, and educational level. Subjects: Women were eligible if they delivered and had newborns weighed within the last 2 years. Total study participants consisted of 32 cases and 34 controls matched for age, parity, and month of delivery. Results: Mothers who consume eggs were 78% less likely to have given birth to a LBW infant (OR 0.22 (95% CI: 0.05?0.87). Mothers with NBW babies had a nonsignificant trend towards higher WDDS. The prevalence of hypertension in mothers who were seen in the clinic at least once over the past 2 years was found to be 27%, and 78% of mothers were not aware of their diagnosis. Conclusion: Enhancing maternal nutrition during pregnancy has broad implications for reducing LBW, improving fetal health and reducing fetal predilection for chronic diseases in adulthood. Longitudinal prospective studies are needed to evaluate the selective benefit of eggs and other high-quality foods in protecting fetal growth. Efforts to improve knowledge and awareness of hypertension in Haiti should be undertaken.

Networks of neurons control feeding and activity patterns by integrating internal metabolic signals of energy balance with external environmental cues such as time-of-day. Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative that molecular players that maintain neuronal coordination of energy homeostasis are identified. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding. These effects lead to increased weight loss, but do not require p75NTR during development. Instead, p75NTR is required for fasting-induced activation of neurons within the arcuate hypothalamus. Indeed, p75NTR specifically in AgRP neurons is required for FAA in response to daytime restricted feeding. These findings establish p75NTR as a novel regulator gating behavioral response to food scarcity and time-of-day dependence of circadian food anticipation.

Estimating the expectation value of an operator corresponding to an observable is a fundamental task in quantum computation. It is often impossible to obtain such estimates directly, as the computer is restricted to measuring in a fixed computational basis. One common solution splits the operator into a weighted sum of Pauli operators and measures each separately, at the cost of many measurements. An improved version collects mutually commuting Pauli operators together before measuring all operators within a collection simultaneously. The effectiveness of doing this depends on two factors. Firstly, we must understand the improvement offered by a given arrangement of Paulis in collections. In our work, we propose two natural metrics for quantifying this, operating under the assumption that measurements are distributed optimally among collections so as to minimise the overall finite sampling error. Motivated by the mathematical form of these metrics, we introduce $\large{S}$ORTED $\large{I}$NSERTION, a collecting strategy that exploits the weighting of each Pauli operator in the overall sum. Secondly, to measure all Pauli operators within a collection simultaneously, a circuit is required to rotate them to the computational basis. In our work, we present two efficient circuit constructions that suitably rotate any collection of $\boldsymbol{k}$ independent commuting $\boldsymbol{n}$-qubit Pauli operators using at most $\boldsymbol{kn-k(k+1)/2}$ and $\boldsymbol{O(kn/\log k)}$ two-qubit gates respectively. Our methods are numerically illustrated in the context of the Variational Quantum Eigensolver, where the operators in question are molecular Hamiltonians. As measured by our metrics, $\large{S}$ORTED $\large{I}$NSERTION outperforms four conventional greedy colouring algorithms that seek the minimum number of collections.

BackgroundOlder adults with serious mental illness (SMI) often have multiple comorbidities and complex medication schedules. Shortages of behavioral health specialists (BHSs), especially in rural areas, frequently make primary care providers (PCPs) the only clinician managing this complex population. The aim of this study was to describe rural/urban psychiatric medication prescribing in older adults with SMI by PCPs and BHSs, and by clinician type.MethodsThis retrospective descriptive analysis used 2018 Medicare data to identify individuals with a bipolar, major depression, schizophrenia, or psychosis diagnosis and examined medication claims for antianxiety, antidepressants, antipsychotics, hypnotics, and anticonvulsants. Descriptive statistics summarized percentage of medications provided by PCPs and BHSs stratified by rural and urban areas and by drug class. Additional analyses compared psychiatric prescribing patterns by physicians, advanced practice registered nurses (APRNs), and physician assistants (PAs).ResultsIn urban areas, PCPs prescribed at least 50% of each psychiatric medication class, except antipsychotics, which was 45.2%. BHSs prescribed 40.7% of antipsychotics and less than 25% of all other classes. In rural areas, percentages of psychiatric medications from PCPs were over 70% for each medication class, except antipsychotics, which was 60.1%. Primary care physicians provided most psychiatric medications, between 36%-57% in urban areas and 47%-65% in rural areas. Primary care APRNs provided up to 13% of prescriptions in rural areas, which was more than the amount prescribed by BHS physicians, expect for antipsychotics. Psychiatric mental health APRNs provided up to 7.5% of antipsychotics in rural areas, but their prescribing contribution among other classes ranged between 1.1%-3.6%. PAs provided 2.5%-3.4% of medications in urban areas and this increased to 3.9%-5.1% in rural areas.ConclusionsResults highlight the extensive roles of PCPs, including APRNs, in managing psychiatric medications for older adults with SMI.

A Lactobacillus-dominated vaginal microbiota (VMB) has been associated with health and considered an important host defense mechanism against urogenital infections. Conversely, depletion of lactobacilli and increased microbial diversity, amplifies the risk of adverse gynecologic and obstetric outcomes. A common clinical condition that exemplifies dysbiosis is bacterial vaginosis (BV). BV is currently treated with antibiotics, but frequently recurs, due in part to persistent dysbiosis and failure of lactobacilli to repopulate the vagina. New treatment options are needed to address BV. The VMB is relatively simple and optimally dominated by one or several species of Lactobacillus. Lactobacillus crispatus is strongly associated with vaginal health and depleted in dysbiosis. Replenishing the dysbiotic VMB with protective L. crispatus CTV-05 is a promising approach to prevent recurrent infections and improve women's health. Here we discuss confirmation of this approach with the microbiome-based biologic drug, LACTIN-V (L. crispatus CTV-05), focusing on prevention of BV recurrence.

We have developed "Microscope-Cockpit" (Cockpit), a highly adaptable open source user-friendly Python-based Graphical User Interface (GUI) environment for precision control of both simple and elaborate bespoke microscope systems. The user environment allows next-generation near instantaneous navigation of the entire slide landscape for efficient selection of specimens of interest and automated acquisition without the use of eyepieces. Cockpit uses "Python-Microscope" (Microscope) for high-performance coordinated control of a wide range of hardware devices using open source software. Microscope also controls complex hardware devices such as deformable mirrors for aberration correction and spatial light modulators for structured illumination via abstracted device models. We demonstrate the advantages of the Cockpit platform using several bespoke microscopes, including a simple widefield system and a complex system with adaptive optics and structured illumination. A key strength of Cockpit is its use of Python, which means that any microscope built with Cockpit is ready for future customisation by simply adding new libraries, for example machine learning algorithms to enable automated microscopy decision making while imaging.

BackgroundBacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis.MethodsWe conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12.ResultsA total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, L. crispatus CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups.ConclusionsThe use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).

ObjectivesIn 2013, the American Society of Addiction Medicine (ASAM) approved its Standards of Care for the Addiction Specialist Physician. Subsequently, an ASAM Performance Measures Panel identified and prioritized the standards to be operationalized into performance measures. The goal of this study is to describe the process of operationalizing 3 of these standards into quality measures, and to present the initial measure specifications and results of pilot testing these measures in a large health care system. By presenting the process rather than just the end results, we hope to shed light on the measure development process to educate, and also to stimulate debate about the decisions that were made.MethodsEach measure was decomposed into major concepts. Then each concept was operationalized using commonly available administrative data sources. Alternative specifications examined and sensitivity analyses were conducted to inform decisions that balanced accuracy, clinical nuance, and simplicity. Using data from the US Veterans Health Administration (VHA), overall performance and variation in performance across 119 VHA facilities were calculated.ResultsThree measures were operationalized and pilot tested: pharmacotherapy for alcohol use disorder, pharmacotherapy for opioid use disorder, and timely follow-up after medically managed withdrawal (aka detoxification). Each measure was calculable with available data, and showed ample room for improvement (no ceiling effects) and wide facility-level variability.ConclusionsNext steps include conducting feasibility and pilot testing in other health care systems and other contexts such as standalone addiction treatment programs, and also to study the specification and predictive validity of these measures.