Monaghanlauridsen7226
We propose a new method for multivariate response regression and covariance estimation when elements of the response vector are of mixed types, for example some continuous and some discrete. Our method is based on a model which assumes the observable mixed-type response vector is connected to a latent multivariate normal response linear regression through a link function. We explore the properties of this model and show its parameters are identifiable under reasonable conditions. We impose no parametric restrictions on the covariance of the latent normal other than positive definiteness, thereby avoiding assumptions about unobservable variables which can be difficult to verify in practice. To accommodate this generality, we propose a novel algorithm for approximate maximum likelihood estimation that works "off-the-shelf" with many different combinations of response types, and which scales well in the dimension of the response vector. Our method typically gives better predictions and parameter estimates than fitting separate models for the different response types and allows for approximate likelihood ratio testing of relevant hypotheses such as independence of responses. The usefulness of the proposed method is illustrated in simulations; and one biomedical and one genomic data example.In two studies, we examined whether open science practices, such as making materials, data, and code of a study openly accessible, positively affect public trust in science. Furthermore, we investigated whether the potential trust-damaging effects of research being funded privately (e.g. by a commercial enterprise) may be buffered by such practices. BI-2493 datasheet After preregistering six hypotheses, we conducted a survey study (Study 1; N = 504) and an experimental study (Study 2; N = 588) in two German general population samples. In both studies, we found evidence for the positive effects of open science practices on trust, though it should be noted that in Study 2, results were more inconsistent. We did not however find evidence for the aforementioned buffering effect. We conclude that while open science practices may contribute to increasing trust in science, the importance of making use of open science practices visible should not be underestimated.
Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs).
Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method.
Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48,p < 0.01), while African American (OR 6.87,p = 0.02) and Asian race (OR 3.12,p ≤ 0.01), signet ring cells on biopsy (OR 3.14,p < 0.01), and distal tumors (OR 1.62,p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1).
Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates amongSNH patients.
Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients.Informal settlements (high population density areas at the outskirts of urban areas characterized by lack basic amenities) in South Africa are consequences of apartheid regime's discriminatory migrant labour and spatial policy and continue to grow. Living in informal settlements accompanies a mire of social/health challenges that threatens upward mobility, but few studies exist that document drivers of mental health challenges in these settings. We investigated the prevalence and social determinants of poor mental health for young men in informal settlements adjacent to one of the largest cities that is at the heart of HIV endemic in South Africa. This study involved a cross-sectional study with cluster sampling design of 674 young men aged 18-30 years residing in eThekwini informal settlement communities. We assessed the prevalence, and social determinants, of significant depressive (i.e., depression) and post-traumatic stress (i.e., PTS) symptoms using logistic regression. Given the complex survey design ofdividual, interpersonal, and social variables that contribute to poor mental health are needed.Cisplatin was originally discovered through its antibacterial action and subsequently has found use as a potent broad-spectrum anticancer agent. This study determines the effect of growth media and solvent on the antibacterial activity of cisplatin and its analogue, oxaliplatin. Escherichia coli MG1655 or MG1655 ΔtolC was treated with the platinum compounds under different conditions and susceptibility was determined. Our results showed that DMSO reduced the activity of cisplatin by fourfold (MIC 12·5 mg l-1 ) compared with 0·9% NaCl-solubilized cisplatin (MIC 3·12 mg l-1 ) when tested in MOPS. Surprisingly, complete loss of activity was observed in Mueller-Hinton Broth II (MHB II). By supplementing MOPS with individual components of MHB II such as the sulphur-containing amino acids, l-cysteine and l-methionine, individually or in combination reduced activity by ≥8-fold (MIC ≥25 mg l-1 ). Oxaliplatin was less active against E. coli (MIC 100 mg l-1 ) but exhibited similar inactivation in the presence of DMSO, MHBII or MOPS spiked with l-cysteine and l-methionine (MIC ≥400 mg l-1 ). Our data suggest that the antibacterial activity of cisplatin and oxaliplatin is modulated by both choice of solvent and composition of growth media. We demonstrate that this is primarily due to sulphur-containing amino acids cysteine and methionine, an essential component of the recommended media for testing antimicrobial susceptibility, MHBII.
Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized.
To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis.
This cross-sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self-reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps.
Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (3 psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis.
Body surface gastric mapping (BSGM) is a new clinical tool for gastric motility diagnostics, providing high-resolution data on gastric myoelectrical activity. Artifact contamination was a key challenge to reliable test interpretation in traditional electrogastrography. This study aimed to introduce and validate an automated artifact detection and rejection system for clinical BSGM applications.
Ten patients with chronic gastric symptoms generated a variety of artifacts according to a standardized protocol (176 recordings) using a commercial BSGM system (Alimetry, New Zealand). An automated artifact detection and rejection algorithm was developed, and its performance was compared with a reference standard comprising consensus labeling by 3 analysis experts, followed by comparison with 6 clinicians (3 untrained and 3 trained in artifact detection). Inter-rater reliability was calculated using Fleiss' kappa.
Inter-rater reliability was 0.84 (95% CI0.77-0.90) among experts, 0.76 (95% CI0.68-0.83) among untrained clinicians, and 0.71 (95% CI0.62-0.79) among trained clinicians. The sensitivity and specificity of the algorithm against experts was 96% (95% CI91%-100%) and 95% (95% CI90%-99%), respectively, vs 77% (95% CI68%-85%) and 99% (95% CI96%-100%) against untrained clinicians, and 97% (95% CI92%-100%) and 88% (95% CI82%-94%) against trained clinicians.
An automated artifact detection and rejection algorithm was developed showing >95% sensitivity and specificity vs expert markers. This algorithm overcomes an important challenge in the clinical translation of BSGM and is now being routinely implemented in patient test interpretations.
An automated artifact detection and rejection algorithm was developed showing >95% sensitivity and specificity vs expert markers. This algorithm overcomes an important challenge in the clinical translation of BSGM and is now being routinely implemented in patient test interpretations.
To reveal the possible routine of brain network dynamic alterations in patients with mesial temporal lobe epilepsy (mTLE) and to establish a predicted model of seizure recurrence during interictal periods.
Seventy-nine unilateral mTLE patients with hippocampal sclerosis and 97 healthy controls from two centers were retrospectively enrolled. Dynamic brain configuration analyses were performed with resting-state functional magnetic resonance imaging (MRI) data to quantify the functional stability over time and the dynamic interactions between brain regions. Relationships between seizure frequency and ipsilateral hippocampal module allegiance were evaluated using a machine learning predictive model.
Compared to the healthy controls, patients with mTLE displayed an overall higher dynamic network, switching mainly in the epileptogenic regions (false discovery rate [FDR] correctedp-FDR < .05). Moreover, the dynamic network configuration in mTLE was characterized by decreased recruitment (intra-network comme. Our study provides novel insights into the brain dynamic network alterations and supports the potential use of DMN dynamic parameters as candidate neuroimaging markers in monitoring the seizure frequency clinically during interictal periods.
Efmoroctocog alfa, the first recombinant factor VIII fusion protein with extended half-life (rFVIII-Fc), has been hypothesized to lower FVIII consumption in patients with severe Haemophilia A (pwSHA), without reducing clinical efficacy. What about real life?
MOTHIF-II was a noninterventional, multicentre, before/after study, via the collection of retrospective data from July 2015 to June 2016 (called T1), and from July 2017 to June 2018 (called T2), in 7 French haemophilia treatment centres. We examined the prescriptions and dispensations of factor VIII and the Annual Bleeding Rate (ABR), in pwSHA without current inhibitors on prophylaxis, before and after the introduction of rFVIII-Fc. The data gathered from the BERHLINGO research database and from the French Healthcare claims database with a determinist pairing process based on the national unique identification number.
A total of 156 pwSHA were included in the prescription cohort and 83 in the ABR cohort. For switched patients, the mean amounts of prescribed FVIII were significantly higher during T1 compared to T2 (4333 (2052) vs.