Predictors of web-based follow-up response in the Prevention of Low Back Pain in the Military Trial (POLM)

<p>Abstract</p> <p>Background</p> <p>Achieving adequate follow-up in clinical trials is essential to establish the validity of the findings. Achieving adequate response rates reduces bias and increases probability that the findings can be generalized to the population of interest. Therefore, the purpose of this study was to determine the influence of attention, demographic, psychological, and health status factors on web-based response rates in the ongoing Prevention of Low Back Pain in the Military (POLM) trial.</p> <p>Methods</p> <p>Twenty companies of Soldiers (n = 4,325) were cluster randomized to complete a traditional exercise program including sit-ups (TEP) with or without a psychosocial educational program (PSEP) or a core stabilization exercise program (CSEP) with or without PSEP. A subgroup of Soldiers (n = 371) was randomized to receive an additional physical and ultrasound imaging (USI) examination of key trunk musculature. As part of the surveillance program, all Soldiers were encouraged to complete monthly surveys via email during the first year. Descriptive statistics of the predictor variables were obtained and compared between responders and non-responders using two sample t-tests or chi-square test, as appropriate. Generalized linear mixed models were subsequently fitted for the dichotomous outcomes to estimate the effects of the predictor variables. The significance level was set at .05 a priori.</p> <p>Results</p> <p>The overall response rate was 18.9% (811 subjects) for the first year. Responders were more likely to be older, Caucasian, have higher levels of education and income, reservist military status, non smoker, lower BMI, and have received individualized attention via the physical/USI examination (p < .05). Age, race/ethnicity, education, military status, smoking history, BMI, and whether a Soldier received the physical/USI examination remained statistically significant (p < .05) when considered in a full multivariate model.</p> <p>Conclusion</p> <p>The overall web based response rate during the first year of the POLM trial was consistent with studies that used similar methodology, but lower when compared to rates expected for standard clinical trials. One year response rate was significantly associated with demographic characteristics, health status, and individualized attention via additional testing. These data may assist for planning of future trials that use web based response systems.</p> <p>Trial Registration</p> <p>This study has been registered at reports at <url>http://clinicaltrials.gov</url> (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00373009">NCT00373009</a>).</p

The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors

The immense molecular diversity of neurons challenges our ability to understand the genetic and cellular etiology of neuropsychiatric disorders. Leveraging knowledge from neurobiology may help parse the genetic complexity: identifying genes important for a circuit that mediates a particular symptom of a disease may help identify polymorphisms that contribute to risk for the disease as a whole. The serotonergic system has long been suspected in disorders that have symptoms of repetitive behaviors and resistance to change, including autism. We generated a bacTRAP mouse line to permit translational profiling of serotonergic neurons. From this, we identified several thousand serotonergic-cell expressed transcripts, of which 174 were highly enriched, including all known markers of these cells. Analysis of common variants near the corresponding genes in the AGRE collection implicated the RNA binding protein CELF6 in autism risk. Screening for rare variants in CELF6 identified an inherited premature stop codon in one of the probands. Subsequent disruption of Celf6 in mice resulted in animals exhibiting resistance to change and decreased ultrasonic vocalization as well as abnormal levels of serotonin in the brain. This work provides a reproducible and accurate method to profile serotonergic neurons under a variety of conditions and suggests a novel paradigm for gaining information on the etiology of psychiatric disorders

Integrating Functional and Diffusion Magnetic Resonance Imaging for Analysis of Structure-Function Relationship in the Human Language Network

The capabilities of magnetic resonance imaging (MRI) to measure structural and functional connectivity in the human brain have motivated growing interest in characterizing the relationship between these measures in the distributed neural networks of the brain. In this study, we attempted an integration of structural and functional analyses of the human language circuits, including Wernicke's (WA), Broca's (BA) and supplementary motor area (SMA), using a combination of blood oxygen level dependent (BOLD) and diffusion tensor MRI.Functional connectivity was measured by low frequency inter-regional correlations of BOLD MRI signals acquired in a resting steady-state, and structural connectivity was measured by using adaptive fiber tracking with diffusion tensor MRI data. The results showed that different language pathways exhibited different structural and functional connectivity, indicating varying levels of inter-dependence in processing across regions. Along the path between BA and SMA, the fibers tracked generally formed a single bundle and the mean radius of the bundle was positively correlated with functional connectivity. However, fractional anisotropy was found not to be correlated with functional connectivity along paths connecting either BA and SMA or BA and WA. for use in diagnosing and determining disease progression and recovery

DYX1C1 is required for axonemal dynein assembly and ciliary motility

DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2–4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4)

Pre-treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-food chain

The enormous quantity of food wastes discarded annually force to look for alternatives for this interesting feedstock. Thus, food bio-waste valorisation is one of the imperatives of the nowadays society. This review is the most comprehensive overview of currently existing technologies and processes in this field. It tackles classical and innovative physical, physico-chemical and chemical methods of food waste pre-treatment and extraction for recovery of added value compounds and detection by modern technologies and are an outcome of the COST Action EUBIS, TD1203 Food Waste Valorisation for Sustainable Chemicals, Materials and Fuels

Outcomes of Immune Checkpoint Inhibitor Administration in Hospitalized Patients With Solid Tumor Malignancies

PURPOSE: More oncologists desire to treat their patients with immune checkpoint inhibitors (ICIs) in the inpatient setting as their use has become more widespread for numerous oncologic indications. This is cost-prohibitive to patients and institutions because of high drug cost and lack of reimbursement in the inpatient setting. We sought to examine current practice of inpatient ICI administration to determine if and in which clinical scenarios it may provide significant clinical benefit and therefore be warranted regardless of cost. METHODS: We conducted a retrospective chart review of adult patients who received at least one dose of an ICI for treatment of an active solid tumor malignancy during hospitalization at a single academic medical center between January 2017 and June 2018. Patient, disease, and admission characteristics including mortality data were examined, and cost analysis was performed. RESULTS: Sixty-five doses of ICIs were administered to 58 patients during the study period. Nearly 40% and 80% of patients died within 30 days and 180 days of ICI administration, respectively. There was a trend toward longer overall survival in patients with good prognostic factors including positive programmed death-ligand 1 (PD-L1) expression or microsatellite instability-high (MSI-H) status. Slightly over 70% of patients were discharged within 7 days of ICI administration. The total cost of inpatient ICI administration over the 18-month study period was $615,016 US dollars. CONCLUSION: Inpatient ICI administration is associated with high costs and poor outcomes in acutely ill hospitalized patients with advanced solid tumor malignancies and therefore should largely be avoided. Careful discharge planning to expedite outpatient treatment after discharge will be paramount in ensuring patients with good prognostic features who will benefit most from ICI therapy can be promptly treated in the outpatient setting as treating very close to discharge in the inpatient setting appears to be unnecessary, regardless of tumor features