Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
22,875
result(s) for
"Sykes, A."
Sort by:
The Effects of Youth Mentoring Programs: A Meta-analysis of Outcome Studies
Mentoring programs, which pair youth with caring, non-parental adults with the goal of promoting positive youth development, are an increasingly popular strategy for early intervention with at-risk youth. However, important questions remain about the extent to which these interventions improve youth outcomes. The present study involved a comprehensive meta-analysis of all outcome studies of intergenerational, one-on-one youth mentoring programs written in the English language between 1975 and 2017, using rigorous inclusion criteria designed to align with developmental theories of youth mentoring. Analysis of 70 mentoring outcome studies, with a sample size of 25,286 youth (average age of 12 years old), yielded a statistically significant effect of mentoring programs across all youth outcomes. The observed effect size fell within the medium/moderate range according to empirical guidelines derived from universal prevention programs for youth, and was consistent with past meta-analyses of youth mentoring. Moderation analyses indicated that programs serving a larger proportion of male youth, deploying a greater percentage of male mentors or mentors with a helping profession background, and requiring shorter meetings yielded larger effect sizes, as did evaluations that relied on questionnaires and youth self-report. Taken together, these findings provide some support for the efficacy of mentoring interventions, while also emphasizing the need to remain realistic about the modest impact of these programs as currently implemented, and highlighting opportunities for improving the quality and rigor of mentoring practices.
Journal Article
لعنة آدم : \العلم الذي يكشف عن مصيرنا الوراثي\
قرأت منذ سنوات كتاب سبع بنات لحواء لنفس المؤلف المتخصص في علم الوراثة بريان سايكس والذي نشر في مكتبة الأسرة في عهد سمير سرحان في هذا الكتاب سبع بنات لحواء يعرض سايكس كيف أمكن التوصل لحل العديد من الغاز التاريخ وأصول الإنسان عبر جينات الميتوكوندريا حيث إن جيناتها تورث فقط من خلال الأم وبالتالي فهي تورث كما هي دون تغيير باستثناء الطفرات التي قد تحدث بها والتي وان حدثت فإنه أيضا تكون هناك ثمة قرابة بل ويعكس معدل الطفرات زمن معيشة الأم الأولى... وفي النهاية توصل إلى إرجاع أصل الأوروبيين إلى سبع أمهات في هذا الكتاب لعنة آدم يكرر سايكس نفس الفكرة ولكن على جينات أخرى تورث من الرجال فقط هذه المرة. . هي الجينات الموجودة على كروموسوم واي ويبدأ في الكشف عن أصول بعض العائلات ومنهم عائلته نفسها ويحاول أن يقارن بين نتائجه التي توصل إليها مسبقا في كتابه الأول عن جينات الميتوكوندريا المورثة من الأم فقط بنتائجه في كتابه الثاني عن جينات كروموسوم واىوأيولىوآي المورثة عبر الأب فقط... ويتطرق إلى مستقبل الذكور في العالم... وهل تفيد هذه التقنية في تفسير ظواهر مثل غلبة الإناث أو الذكور في بعض العائلات. . وضعف الحيوانات المنوية لدى البعض.. والشذوذ الجنسي... والاستنساخ يندر أن تجد ترجمة عربية سلسة غير منفرة للمواد العلمية... المترجم للكتابين مصطفى إبراهيم فهمي أحد القلائل جدا الذين يترجمون العلوم باحتراف دون فذلكة للمصطلحات ودون أي اشتقاقات غريبة وبإضافة حواش مختصرة تصيب أهدافها.
Book
Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors
Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D
2
receptor. However, support for this hypothesis is limited to a relatively small number of observations made across several decades and under different experimental conditions. Here we show that association rates, but not dissociation rates, correlate with EPS. We measured the kinetic binding properties of a series of typical and atypical APDs in a novel time-resolved fluorescence resonance energy transfer assay, and correlated these properties with their EPS and prolactin-elevating liabilities at therapeutic doses. EPS are robustly predicted by a rebinding model that considers the microenvironment of postsynaptic D
2
receptors and integrates association and dissociation rates to calculate the net rate of reversal of receptor blockade. Thus, optimizing binding kinetics at the D
2
receptor may result in APDs with improved therapeutic profile.
Atypical antipsychotics show reduced extrapyramidal side effects compared to first generation drugs. Here the authors use time-resolved FRET to measure binding kinetics, and show that side effects correlate with drug association rates to the D
2
receptor, while dissociation rates correlate with prolactin elevation.
Journal Article
Mechanism of hard-nanomaterial clearance by the liver
The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 ± 6.4%), hepatic B cells (81.5 ± 9.3%) and liver sinusoidal endothelial cells (64.6 ± 13.7%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 ± 10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.
The blood clearance mechanism, by the liver, of administered hard nanomaterials is reported in relation to blood flow dynamics, organ microarchitecture and cellular phenotype.
Journal Article
The role of kinetic context in apparent biased agonism at GPCRs
Biased agonism describes the ability of ligands to stabilize different conformations of a GPCR linked to distinct functional outcomes and offers the prospect of designing pathway-specific drugs that avoid on-target side effects. This mechanism is usually inferred from pharmacological data with the assumption that the confounding influences of observational (that is, assay dependent) and system (that is, cell background dependent) bias are excluded by experimental design and analysis. Here we reveal that ‘kinetic context’, as determined by ligand-binding kinetics and the temporal pattern of receptor-signalling processes, can have a profound influence on the apparent bias of a series of agonists for the dopamine D
2
receptor and can even lead to reversals in the direction of bias. We propose that kinetic context must be acknowledged in the design and interpretation of studies of biased agonism.
Biased agonists act at a receptor to preferentially induce distinct intracellular signalling responses over others. Here the authors show how kinetics of ligand binding and signaling responses greatly influence observed bias profiles, and hence must be considered when studying biased agonists.
Journal Article
Tailoring nanoparticle designs to target cancer based on tumor pathophysiology
Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes.
Journal Article
The impact of Duration of Untreated Psychosis on functioning and quality of life over one year of Coordinated Specialty Care (CSC)
This study examined the relationship between the Duration of Untreated Psychosis (DUP) and functional outcomes at baseline, 6 months, and 12 months after admission to Coordinated Specialty Care (CSC).
A total of 246 participants from two U.S. public-sector CSC programs were categorized into Low and High DUP groups using two criteria: (i) a median split of the DUP distribution and (ii) the World Health Organization (WHO) aspirational standard of 3 months. Changes in global functioning (GAF), social functioning (GF: Social), and occupational functioning (GF: Role), symptom severity (PANSS), and quality of life (QoL) were assessed using a Linear Mixed Model Repeated Measures (MMRM) analysis across the three time points. A Generalized Linear Model (GLM) with a logit link function was applied to analyze binary outcomes, specifically the status of being Neither in the Labor Force, Education, or Training (NLFET). Both models adjusted for time and site as covariates and used an unstructured variance-covariance matrix to account for within-subject correlations in repeated measures. The difference-in-differences method was employed to estimate the impact of DUP on outcomes over time, with results reported as least square means for continuous outcomes, odds ratios for binary outcomes, and 95% confidence intervals (CI) for both Low and High DUP groups.
No significant differences were observed between the Low and High DUP groups at baseline. By 6 months, participants in the Low DUP group (DUP < 3 months) exhibited significantly greater improvements (reduction) in NLFET status (3-month OR = 3.25, p = 0.03; median split OR = 2.25, p = 0.03) and global functioning, GF: Role, and GF: Social. By 12 months, the Low DUP group continued to show significantly greater NLFET status improvement (3-month OR = 3.59, p = 0.03; median split OR = 3.40, p = 0.0032). Improvements in global functioning were sustained at 12 months, while social and occupational functioning gains were not. No significant differences were observed between groups for quality of life or symptom severity over time.
Shorter DUP is linked to more rapid functional recovery within the first year after CSC admission.
Journal Article
The impact of obstructive sleep apnea on exercise capacity in a cardiac rehabilitation program
PurposeCardiac rehabilitation (CR) improves clinical outcomes in patients with cardiovascular disease (CDV). Patients with CVD often have multiple comorbidities, including obstructive sleep apnea (OSA), potentially affecting their ability to participate and achieve functional improvement during CR. We aimed to test the hypothesis that OSA reduces peak exercise capacity (EC) in patients undergoing CR and to explore if OSA treatment modifies this relationship.MethodsData from a retrospective cohort of CR patients was analyzed. OSA was defined as a respiratory event index > 5/h or physician diagnosis. Patients with OSA were considered “treated” if using continuous positive airway pressure regularly during the CR period. Change in METs was the primary study outcome.ResultsAmong 312 CR patients, median age of 67 years, 103 (33%) had known OSA (30 treated, 73 untreated). Patients with OSA vs. those with no OSA were more likely to be obese and male; otherwise, groups were similar. Compared with the no OSA group, patients with OSA had lower pre-CR METs (3.3 [2.9–4.5] vs. 3.9 [3.1–5], P = .01) and lower post-CR METs (5.3 [4–7] vs. 6 [4.6–7.6], P = .04), but achieved a similar increase in METs post-CR (1.8 [0.6–2.6] vs. 2.0 [0.9–3], P = .22). Furthermore, compared to no OSA, pre-CR and post-CR METs tended to be similar in patients with treated OSA, but lower in untreated patients, with similar increases in METs across all groups, even when adjusting for covariates via multivariable regression.ConclusionOSA is prevalent in patients with CVD undergoing CR. CR substantially improves exercise capacity independent of OSA status, but screening for—and treatment of—OSA may improve the absolute exercise capacity achieved through CR.
Journal Article
Prolonged Monkeypox Virus Infections, California, USA, May 2022–August 2024
Monkeypox virus (MPXV) infection typically lasts 14-28 days. Prolonged MPXV infection, in which symptoms or test positivity last >28 days, has been documented but not fully characterized. We used the California Department of Public Health (California, USA) mpox registry to compare prolonged (>28 days) and nonprolonged (<28 days) mpox cases by demographics, HIV status, and JYNNEOS vaccination status. Of 6,469 cases, 82 (1.3%) were prolonged. Persons with prolonged MPXV infections were more likely to be Black or African American (prolonged, 20.7%, vs. nonprolonged, 11.6%) and to have HIV (prolonged, 61.0%, vs. nonprolonged, 39.9%). Among persons with HIV, prolonged infections were more likely among those with lower (<200) CD4 counts (prolonged, 10.0%, vs. nonprolonged, 3.9%) or not engaged in HIV care (prolonged, 46.0%, vs. nonprolonged, 18.1%). No prolonged infections occurred in persons who received 2 JYNNEOS vaccine doses. Groups disproportionately affected by prolonged mpox should be prioritized for mpox vaccine education and outreach.
Journal Article