Fatigue Testing a Mechanized Percussion Well Drilling System for Water Access in Western Africa

The Mechanized Percussion Well Drilling (MPWD) Collaboratory project seeks to design a simple mechanized well drilling system for drilling shallow water wells in Western Africa. Our client, Open Door Development (ODD), seeks to make water accessible to all in the region, but has had difficulty drilling through hard soil layers. To combat this problem, the MPWD team has worked closely with Mr. Joseph Longenecker to develop a mechanized percussion well drilling rig that is capable of drilling through these harder layers. Currently, the MPWD team is seeking to provide recommendations to improve the lifetime of our client’s new, fully mechanized rig design. This year, our team’s work has been focused specifically on analyzing the lifetime of the rig’s driveline chains and also on its frame. For the driveline chains, the team will be conducting fatigue testing on a model of the driveline system to determine which type of chain should be used on the rig. To determine the lifetime of the frame, the team will be performing a series of static, buckling, and fatigue finite element analyses on the rig’s frame. The most recent accomplishments of the MPWD team have nearly proved that their design for the loading application will be feasible for use on the actual testing rig and that multiple studies of finite element analysis can be performed to simulate the different rig frame loading scenarios.https://mosaic.messiah.edu/engr2021/1019/thumbnail.jp

Systematic Overestimation of Machine Learning Performance in Neuroimaging Studies of Depression

We currently observe a disconcerting phenomenon in machine learning studies in psychiatry: While we would expect larger samples to yield better results due to the availability of more data, larger machine learning studies consistently show much weaker performance than the numerous small-scale studies. Here, we systematically investigated this effect focusing on one of the most heavily studied questions in the field, namely the classification of patients suffering from Major Depressive Disorder (MDD) and healthy controls. Drawing upon a balanced sample of $N = 1,868$ MDD patients and healthy controls from our recent international Predictive Analytics Competition (PAC), we first trained and tested a classification model on the full dataset which yielded an accuracy of 61%. Next, we mimicked the process by which researchers would draw samples of various sizes ($N=4$ to $N=150$) from the population and showed a strong risk of overestimation. Specifically, for small sample sizes ($N=20$), we observe accuracies of up to 95%. For medium sample sizes ($N=100$) accuracies up to 75% were found. Importantly, further investigation showed that sufficiently large test sets effectively protect against performance overestimation whereas larger datasets per se do not. While these results question the validity of a substantial part of the current literature, we outline the relatively low-cost remedy of larger test sets

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar afective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratifcation are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identifed genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × ­10−3; FDR< 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common infammatory/autoimmune processes, our fndings strongly suggest that HLA-mediated low infammatory background may contribute to the efcient response to Li in BD patients, while an infammatory status overriding Li anti-infammatory properties would favor a weak response

Many Neglected Tropical Diseases May Have Originated in the Paleolithic or Before: New Insights from Genetics

The standard view of modern human infectious diseases is that many of them arose during the Neolithic when animals were first domesticated, or afterwards. Here we review recent genetic and molecular clock estimates that point to a much older Paleolithic origin (2.5 million years ago to 10,000 years ago) of some of these diseases. During part of this ancient period our early human ancestors were still isolated in Africa. We also discuss the need for investigations of the origin of these diseases in African primates and other animals that have been the original source of many neglected tropical diseases

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD

Hearing Loss in Stranded Odontocete Dolphins and Whales

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70–90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested

In-Orbit Performance of the GRACE Follow-on Laser Ranging Interferometer

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1 nm/Hz at Fourier frequencies above 100 mHz. © 2019 authors. Published by the American Physical Society

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

From multivariate methods to an AI ecosystem

Depression constitutes a leading cause of disability worldwide. Despite extensive research on its interaction with psychobiological factors, associated pathways are far from being elucidated. Metabolomics, assessing the final products of complex biochemical reactions, has emerged as a valuable tool for exploring molecular pathways. We conducted a metabolome-wide association analysis to investigate the link between the serum metabolome and depressed mood (DM) in 1411 participants of the KORA (Cooperative Health Research in the Augsburg Region) F4 study (discovery cohort). Serum metabolomics data comprised 353 unique metabolites measured by Metabolon. We identified 72 (5.1%) KORA participants with DM. Linear regression tests were conducted modeling each metabolite value by DM status, adjusted for age, sex, body-mass index, antihypertensive, cardiovascular, antidiabetic, and thyroid gland hormone drugs, corticoids and antidepressants. Sensitivity analyses were performed in subcohorts stratified for sex, suicidal ideation, and use of antidepressants. We replicated our results in an independent sample of 968 participants of the SHIP-Trend (Study of Health in Pomerania) study including 52 (5.4%) individuals with DM (replication cohort). We found significantly lower laurylcarnitine levels in KORA F4 participants with DM after multiple testing correction according to Benjamini/Hochberg. This finding was replicated in the independent SHIP-Trend study. Laurylcarnitine remained significantly associated (p value &amp;lt; 0.05) with depression in samples stratified for sex, suicidal ideation, and antidepressant medication. Decreased blood laurylcarnitine levels in depressed individuals may point to impaired fatty acid oxidation and/or mitochondrial function in depressive disorders, possibly representing a novel therapeutic target