Advanced Signal Processing Techniques for Fault Detection and Diagnosis in a Wind Turbine Induction Generator Drive Train: A Comparative Study

International audienceThis paper deals with the diagnosis of Wind Turbines based on generator current analysis. It provides a comparative study between traditional signal processing methods, such as periodograms, with more sophisticated approaches. Performances of these techniques are assessed through simulation experiments and compared for several types of fault, including air-gap eccentricities, broken rotor bars and bearing damages

A Discrete Class of Intergenic DNA Dictates Meiotic DNA Break Hotspots in Fission Yeast

Meiotic recombination is initiated by DNA double-strand breaks (DSBs) made by Spo11 (Rec12 in fission yeast), which becomes covalently linked to the DSB ends. Like recombination events, DSBs occur at hotspots in the genome, but the genetic factors responsible for most hotspots have remained elusive. Here we describe in fission yeast the genome-wide distribution of meiosis-specific Rec12-DNA linkages, which closely parallel DSBs measured by conventional Southern blot hybridization. Prominent DSB hotspots are located ∼65 kb apart, separated by intervals with little or no detectable breakage. Most hotspots lie within exceptionally large intergenic regions. Thus, the chromosomal architecture responsible for hotspots in fission yeast is markedly different from that of budding yeast, in which DSB hotspots are much more closely spaced and, in many regions of the genome, occur at each promoter. Our analysis in fission yeast reveals a clearly identifiable chromosomal feature that can predict the majority of recombination hotspots across a whole genome and provides a basis for searching for the chromosomal features that dictate hotspots of meiotic recombination in other organisms, including humans

Using Indium-111 labeled radiopharmaceuticals to target the BB2 receptor on human prostate cancer cells [abstract]

Abstract only availableThe BB2 receptor, belonging to the Bombesin receptor family, has been shown to be highly over expressed in a variety of cancer cell lines, including human prostate cancer. Our laboratory have been involved, for over a decade, in synthesizing Bombesin analogues that target the BB2 receptor for the purpose of developing radiopharmaceuticals for diagnostic and/or therapeutic treatment of cancer. Radiopharmaceuticals based on Bombesin are typically composed of a chelator, isotope, linking group and targeting vector [See Bifunctional Conjugate Design [figure below]. Previous studies by our group and others have shown that variations in linking groups affect the retention time of the bifunctional conjugate in prostate cancer (PC-3) cells. Higher retention time allows for more efficacious therapeutic benefits and enhanced diagnostic imaging capabilities. In this study, we seek to determine the pharmacokinetic benefits achieved in altering the linking group using aliphatic and aromatic linking groups. In-vitro analysis of the radiopharmaceuticals studied found that the Bombesin derivative with the aliphatic linking group demonstrated a slightly higher affinity for the BB2 receptor compared to the Bombesin analogs containing aromatic linking groups. In vivo pharmacokinetic and imaging studies were performed using pre-clinical models of prostate cancer. The tumor uptake of the Bombesin derivatives with the aromatic linking groups were found to be significantly higher compared to that of the Bombesin derivative with the aliphatic linking group. In contrast, the aromatic Bombesin analogs also exhibited higher amounts of undesirable accumulation in the kidneys and other non-target tissues. In conclusion, we found that the aliphatic compounds were more appropriate for diagnostic imaging of prostate cancer due to the reduced non-target retention. The Bombesin analogs with aromatic linking groups showed potential for use as therapeutic agents for prostate cancer treatment.National Institutes of Health Molecular Imaging Progra

Targeting the BB2 receptor on human prostate cancer cells using Indium-111 labeled radiopharmaceutical [abstract]

Abstract only availableFaculty Mentor: Dr. Timothy Hoffman, Internal MedicineThe BB2 receptor, belonging to the Bombesin receptor family, has been shown to be highly over expressed in a variety of cancer cell lines, including human prostate cancer. Over expression of the BB2 receptor offers an appealing target for the design of targeted radiopharmaceuticals.  The Hoffman laboratory and others have been involved, for over a decade, in synthesizing Bombesin analogues that target the BB2 receptor for the purpose of developing a viable radiopharmaceutical for diagnostic or therapeutic treatment of cancer. Radiopharmaceuticals based on Bombesin analogues are typically composed of a targeting vector, radioisotope, chelator and linking group [See Bifunctional Conjugate Design figure below]. Previous studies have shown that variations in linking groups may affect the retention time of the bifunctional conjugate in prostate cancer (PC-3) cells.  Higher retention time allows for more efficacious therapeutic benefits and enhanced diagnostic imaging capabilities.  In the work presented, we designed and synthesized a 111In-Bombesin analogue with a phenyl linker group in order to determine if the phenyl linker group would provide higher retention times in prostate cancer.  In-vitro analysis of the radiopharmaceutical was performed using PC-3 cells to determine the affinity of the new compound for the BB2 receptor to be 1.09 nM. In-vivo studies of the radiopharmaceutical were also conducted by injection of the radiopharmaceutical into CF-1 (“normal”) mice, as well as SCID (Severe Combined Immunodeficient) mice bearing 2-3 week old PC-3 tumors. Experimental results on SCID mice revealed uptakes of 6.36, 3.34, 2.42 and 1.69 % Injected Dose of radiopharmaceutical per gram of tumor tissue at 0.25, 1, 4 and 24 hours, respectively. Imaging using Micro-SPECT (Single-Photon Emission Computed Tomography) was performed to track the dispersion of the radiopharmaceutical throughout the mouse model and confirmed the targeted uptake of the radiopharmaceutical

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index.

BACKGROUND: Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. METHODS AND FINDINGS: We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality-no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77-0.81), and in early (AUC = 0.81 95% CI: 0.78-0.83) and late (AUC = 0.84, 95% CI: 0.78-0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60-64 years, overall mortality was estimated at 9% (95% CI: 6-11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3-7%) to 21% (95% CI: 12-31%), depending on sex and comorbid disease. CONCLUSION: Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines

A discrete class of intergenic DNA dictates meiotic DNA break hotspots in fission yeast.

Meiotic recombination is initiated by DNA double-strand breaks (DSBs) made by Spo11 (Rec12 in fission yeast), which becomes covalently linked to the DSB ends. Like recombination events, DSBs occur at hotspots in the genome, but the genetic factors responsible for most hotspots have remained elusive. Here we describe in fission yeast the genomewide distribution of meiosis-specific Rec12-DNA linkages, which closely parallel DSBs measured by conventional Southern blot hybridization. Prominent DSB hotspots are located ;65 kb apart, separated by intervals with little or no detectable breakage. Most hotspots lie within exceptionally large intergenic regions. Thus, the chromosomal architecture responsible for hotspots in fission yeast is markedly different from that of budding yeast, in which DSB hotspots are much more closely spaced and, in many regions of the genome, occur at each promoter. Our analysis in fission yeast reveals a clearly identifiable chromosomal feature that can predict the majority of recombination hotspots across a whole genome and provides a basis for searching for the chromosomal features that dictate hotspots of meiotic recombination in other organisms, including humans

Family systemic psychosocial support for at-risk adolescents in Lebanon: study protocol for a multi-site randomised controlled trial

Background: Adolescents growing up in communities characterised by adversity face multiple risk factors for poor mental health and wellbeing. There is currently a scarcity of research on effective approaches for preventing and treating psychological distress in this population, particularly in humanitarian settings. The powerful impact of the home environment and family support is well known; however, approaches targeting the family are seldom developed or evaluated in such settings. We developed a brief family systemic psychosocial support intervention to be delivered through existing child protection systems with non-specialist facilitators. This paper outlines the study protocol for a randomised controlled trial of the intervention in Lebanon.Methods: We will conduct a single-blind hybrid effectiveness-implementation multi-site RCT comparing the locally developed systemic family intervention to a waitlist control group for families residing in vulnerable regions in North Lebanon and Beqaa governorates (including families of Syrian, Palestinian, and Lebanese backgrounds). Outcomes on a range of family, adolescent, and caregiver measures will be assessed at baseline (T0) and post-intervention (T1), and at a 3-month follow-up for the treatment arm (T2). Families will be eligible for the trial if they are identified by implementing organisations as being medium-to-high risk for child protection concerns and have one or more adolescent aged 12–17 who demonstrates significant psychological distress on a self-report brief screening tool. Families will be randomly assigned to a treatment or a waitlist control condition. Families in the waitlist condition will receive a group version of the programme after completion of the study, to allow us to assess feasibility, acceptability, and preliminary indications of intervention effects of this modality. The primary outcome is reduction in overall adolescent-reported psychological distress over time, with post-intervention (T1) as the primary endpoint. Secondary adolescent-reported outcomes include family functioning, psychosocial wellbeing, and emotional regulation difficulties. Secondary caregiver-reported outcomes include parenting style, family functioning, psychological distress, and emotional regulation difficulties. Discussion: This trial will provide the first assessment of the effectiveness of the family systemic psychosocial support intervention for use in Lebanon, with important implications for the use of systemic, low-cost, non-specialist interventions for this age range. Trial registration: Local registry: National Mental Health Program, Ministry of Public Health, Lebanese Republic. Registered on 19 October 2021 Lebanese Clinical Trial Registry LBCTR2021104870