INFLUENCE OF PUBLIC TENDER REQUIREMENT ON YOUTHS ACCESSIBILITY TO GOVERNMENT PROCUREMENT OPPORTUNITIES NAKURU COUNTY

Youth in accessing Government Tenders opportunity has proven successful around the world. However poor implementation of policies has ensured that the vulnerable populations are more likely to be overlooked by the government, and less likely to receive skills and training. Young people are among the distraught or vested parties in many creating economies. Various studies carried out globally and locally indicate Youths are among the disadvantaged or special interest groups in many developing economies. Globally, the World Bank (2010) indicates that many countries are yet to develop procedural frameworks that ensure: Government tender procedures are transparent and promote equity.  The purpose of this study, therefore, was to assess the influence of public tenders requirements on youth accessibility to government procurement opportunities in Nakuru county. The study specifically attempted to establish the influence of financial capacity, legal requirements, and technical capability on youth accessibility to government procurement opportunities in Nakuru County. The study was anchored on three theories, namely: Resource-based view theory, Institutional Theory, and skill-based theory. The study employed a descriptive survey research design using quantitative approaches. The research targeted 110 youths in Nakuru County. The study used a closed-ended questionnaire in collecting primary data. The questionnaires were pretested to ensure validity and reliability. The collected data were summarized and analyzed using both descriptive and inferential statistics and then presented in tables. The study concluded that financial capacity and legal requirements have a statistically significant influence on the youth's accessibility to government procurement opportunities in Nakuru County. In the context of technical capability, the study concluded that although they have a positive influence on youth’s access to the government tendering process in Nakuru County on their own, the influence is not statistically significant. The study recommends a deeper look into the influence of the various metrics used to examine the influence of financial capacity, legal requirements, and technical capacity on youth accessibility to government procurement opportunities in Nakuru County

Effect of aging in functional redox state of single isolated skeletal muscle fibres

[EN] Skeletal muscle constantly produces reactive oxygen species (ROS). During contractile activity ROS are generated in skeletal muscle fibres. There is considerable support for an involvement of ROS in the process of aging. Several studies indicate that adaptive responses of skeletal muscle that are activated and regulated by ROS are disrupted during aging. The aim of this study was to monitor, in real time, intracellular ROS production in single skeletal muscle fibres from old and young mice and study the effect of contractile activity in these cells. Following evaluate and correlate the potential changes in intracellular ROS production with glutathione redox state and antioxidant enzymatic activities in muscle. Single skeletal muscle fibres were isolated from the Flexor Digitorus Brevis muscle from young (2-4 monthold) and old (26-28 month-old) C57BL/6 mice. Fibres were loaded with DCFH-DA, a fluorophore probe that allows the quantification of intracellular ROS generation by fluorescence microscopy imaging. Contractile activity was induced in fibres by electrical stimulation. Glutathione redox state and activity of antioxidant enzymes were analysed in gastrocnemious muscle. Intracellular basal level of ROS was higher in fibres from old mice. Contractile activity induced increase of ROS generation in fibres from young mice. However, this response was attenuated in fibres from old mice. Glutathione redox state was significant different, in favour of oxidized glutathione, in muscles from old mice. Glutathione peroxidase and catalase activities were significantly augmented in muscles from old mice. In conclusion, the process of aging modifies the basal redox status in skeletal muscle fibres in favour of oxidation and induces adaptation mechanisms of antioxidant defences. These are not able to neutralize the increase of basal oxidation, but they might lead to the attenuation of ROS produced by contractile activity observed in fibres from old mice

Evidence for feasibility of implementing online brief cognitive‐behavioral therapy for eating disorder pathology in the workplace

Objective: CBT-T is a brief (10-week) cognitive-behavioral therapy for non-underweight eating disorders. This report describes the findings from a single center, single group, feasibility trial of online CBT-T in the workplace as an alternative to health service settings. Method: This trial was approved by the Biomedical and Scientific Research Ethics committee, University of Warwick, UK (reference 125/20-21) and was registered with ISRCTN (reference number: ISRCTN45943700). Recruitment was based on self-reported eating and weight concerns rather than diagnosis, potentially enabling access to treatment for employees who have not previously sought help and for those with sub-threshold eating disorder symptoms. Assessments took place at baseline, mid-treatment (week 4), post-treatment (week 10), and follow-up (1 and 3 months post-treatment). Participant experiences following treatment were assessed using quantitative and qualitative approaches. Results: For the primary outcomes, pre-determined benchmarks of high feasibility and acceptability were met, based on recruiting >40 participants (N = 47), low attrition (38%), and a high attendance rate (98%) over the course of the therapy. Participant experiences revealed low previous help-seeking for eating disorder concerns (21%). Qualitative findings indicated a wide range of positive impacts of the therapy and the workplace as the therapeutic setting. Analysis of secondary outcomes for participants with clinical and sub-threshold eating disorder symptoms showed strong effect sizes for eating pathology, anxiety and depression, and moderate effect sizes for work outcomes. Discussion: These pilot findings provide a strong rationale for a fully powered randomized controlled trial to determine the effectiveness of CBT-T in the workplace. Public Significance: This study demonstrates the feasibility of implementing an eating disorders intervention (online CBT-T) in the workplace as an alternative to traditional healthcare settings. Recruitment was based on self-reported eating and weight concerns rather than diagnosis, potentially enabling access to treatment for employees who had not previously sought help. The data also provide insights into recruitment, acceptability, effectiveness, and future viability of CBT-T in the workplace

Involvement of Reactive Oxygen Species (ROS) inskeletal muscle function during ageing: Study in amodel of isolated single skeletal muscle fibre

[ES] Suplemento de la revista Free Radical Biology and Medicine: Involvement of Reactive Oxygen Species (ROS) inskeletal muscle function during ageing: Study in amodel of isolated single skeletal muscle fibre

A feasibility study of the delivery of online brief cognitive-behavioral therapy (CBT-T) for eating disorder pathology in the workplace

Objective CBT-T is a brief (10 sessions) version of cognitive behavioral therapy for non-underweight eating disorders. This report describes the protocol for a single center, single group, feasibility trial of online CBT-T in the workplace as an alternative to the health-service setting. By offering mental health services for eating disorders in the workplace, greater accessibility and increased help-seeking behaviors could be achieved. Method Treatment will be delivered online over 10 weeks and offered to employees based on self-referral rather than meeting diagnostic criteria, making treatment available to employees with sub-threshold eating disorder symptoms. Results Assessments will be conducted at baseline, mid-treatment (week 4), posttreatment (week 10) and at follow-up (1 month and 3 months posttreatment). For the primary outcome, measures will include recruitment, attrition and attendance data using pre-set benchmarks to determine high, medium or low feasibility and acceptability. Qualitative participant experiences data will be analyzed using thematic analysis. Impact on work engagement and effect sizes will be determined from secondary outcome measures; the latter enabling sample size calculations for future study. Discussion These pilot data will provide insights to recruitment, acceptability, effectiveness and viability of a future fully powered clinical trial of online CBT-T in the workplace. Public Significance Statement This study will present feasibility data from an eating disorders intervention (online CBT-T) using the workplace as an alternative to the healthcare setting to recruit and treat workers. Recruitment will be based on self-reported eating and weight concerns rather than diagnosis potentially enabling treatment to employees who have not previously sought help. The data will also provide insights to recruitment, acceptability, effectiveness, and future viability of CBT-T in the workplace

Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<$10^{−4}$). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×$10^{−8}$. Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×$10^{−6}$; Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC

The CHIP-Family study to improve the psychosocial wellbeing of young children with congenital heart disease and their families: design of a randomized controlled trial

Background: Children with congenital heart disease (CHD) are at increased risk for behavioral, emotional, and cognitive problems. They often have reduced exercise capacity and participate less in sports, which is associated with a lower quality of life. Starting school may present more challenges for children with CHD and their families than for families with healthy children. Moreover, parents of children with CHD are at risk for psychosocial problems. Therefore, a family-centered psychosocial intervention for children with CHD when starting school is needed. Until now, the 'Congenital Heart Disease Intervention Program (CHIP) - School' is the only evidence-based intervention in this field. However, CHIP-School targeted parents only and resulted in non-significant, though positive, effects as to child psychosocial wellbeing. Hence, we expanded CHIP by adding a specific child module and including siblings, creating the CHIP-Family intervention. The CHIP-Family study aims to (1) test the effects of CHIP-Family on parental mental health and psychosocial wellbeing of CHD-children and to (2) identify baseline psychosocial and medical predictors for the e

Novel Common Genetic Susceptibility Loci for Colorectal Cancer

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant