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"Kerr, M."
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The association of child maltreatment and systemic inflammation in adulthood: A systematic review
Child maltreatment (CM) is associated with mental and physical health disorders in adulthood. Some studies have identified elevated markers of systemic inflammation in adult survivors of CM, and inflammation may mediate the association between CM and later health problems. However, there are methodological inconsistencies in studies of the association between CM and systemic inflammation and findings are conflicting. We performed a systematic review to examine the association of CM with systemic inflammation in adults.
A pre-registered systematic review was performed following PRISMA guidelines. Medline, Embase, Scopus and PsychInfo were searched for studies of the association of CM with blood markers of inflammation in adults. Quality was assessed using the Crowe Critical Appraisal Tool. We had intended to perform a meta-analysis, but this was not possible due to variation in study design and reporting.
Forty-four articles met criteria for inclusion in the review. The most widely reported biomarkers were C-Reactive Protein (CRP) (n = 27), interleukin-6 (IL-6) (n = 24) and Tumour Necrosis Factor-alpha (TNF-a) (n = 17). Three studies were prospective (all relating to CRP) and the remainder were retrospective. 86% of studies were based in high income countries. In the prospective studies, CM was associated with elevated CRP in adulthood. Results of retrospective studies were conflicting. Methodological issues relating to the construct of CM, methods of analysis, and accounting for confounding or mediating variables (particularly Body Mass Index) may contribute to the uncertainty in the field.
There is some robust evidence from prospective studies that CM is associated with elevated CRP in adulthood. We have identified significant methodological inconsistencies in the literature and have proposed measures that future researchers could employ to improve consistency across studies. Further prospective, longitudinal, research using robust and comparable measures of CM with careful consideration of confounding and mediating variables is required to bring clarity to this field.
Journal Article
Gun violence prevention? : the politics behind policy responses to school shootings in the United States
This book examines the gun-related policy responses to three school shooting incidents in the United States. Gun violence prevention activists and others involved in policy making were interviewed for the book, and news media articles and policy documents were critically assessed. As a result, interpretations of the Second Amendment are shown to affect the acceptability of certain gun restrictions. News media content and policy documents, coupled with the thoughts of activists, also give an indication of why certain policy measures passed and others failed at the time of each of the case studies--back cover.
Book
Association between pathologic response and survival after neoadjuvant therapy in lung cancer
Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary tumor (PT) and lymph nodes (LNs)), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pathologic complete response and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-programmed death protein 1) plus chemotherapy in patients with resectable lung cancer. RVT, regression and necrosis were quantified (0–100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus >0% RVT-PT (hazard ratio = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (area under the curve = 0.74); 2-year EFS rates were 90%, 60%, 57% and 39% for patients with 0–5%, >5–30%, >30–80% and >80% RVT, respectively. Each 1% RVT associated with a 0.017 hazard ratio increase for EFS. Combining pathologic response from PT and LNs helped differentiate outcomes. When compared with radiographic response and circulating tumor DNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted. ClinicalTrials.gov registration:
NCT02998528
.
Analysis of the phase 3 CheckMate 816 trial shows that the depth of pathologic response as assessed by percent residual viable tumor is correlated with event-free survival following neoadjuvant immunotherapy plus chemotherapy, supporting pathologic response as a biomarker of survival.
Journal Article
Death is but a dream : finding hope and meaning at life's end
\"The first book to explore the meaningful dreams and visions that bring comfort as death nears\"-- Provided by publisher.
Book
Comparing and contrasting predictive biomarkers for immunotherapy and targeted therapy of NSCLC
The era of personalized medicine for advanced-stage non-small-cell lung cancer (NSCLC) began when biomarker-based evidence of molecular pathway and/or oncogene addiction of the tumour became mandatory for the allocation of specific targeted therapies. More recently, the immunotherapy revolution, specifically, the development of immune-checkpoint inhibitors (ICIs), has dramatically altered the NSCLC treatment landscape. Herein, we compare and contrast the clinical development of immunotherapy and oncogene-directed therapy for NSCLC, focusing on the role of predictive biomarkers. Immunotherapy biomarkers are fundamentally different from oncogene biomarkers in that they are continuous rather than categorical (binary), spatially and temporally variable and reliant on multiple complex interactions rather than a single, dominant determinant. The performance of predictive biomarkers for ICIs might be improved by combining different markers to reduce the assumptive risks associated with each one. Novel combinations with chemotherapy and ICIs complicate biomarker discovery but do not decrease the value of the markers identified. Perfectly predictive biomarkers of benefit from immunotherapy are unlikely to be identified, although exclusionary biomarkers of minimal benefit or an unacceptable risk of toxicity might be feasible. The clinical adoption and applicability of such biomarkers might vary depending on line of treatment, the available therapeutic alternatives and health economic considerations.The advent of effective molecularly targeted treatments and immunotherapies for non-small-cell lung cancer (NSCLC) has greatly improved patient outcomes. Whereas most patients selected for treatment with molecularly targeted drugs derive benefits from these agents, benefit from immunotherapy is more difficult to predict. Herein, Camidge and colleagues compare and contrast predictive biomarkers for immunotherapy and targeted therapy of NSCLC to highlight considerations for biomarker development.
Journal Article
الأداء الأمثل للشركات
يقدم هذا الكتاب طرقا بسيطة ومباشرة لتطبيق الأفكار الثاقبة في عالم إدارة النظم الاقتصادية الجديدة كما أنه يقدم حلولا شاملة للمشكلات الأساسية التي يواجهها مديرون الشركات فيما يتعلق بالموظفين وعمليات التشغيل والوسائل التكنولوجية ويكشف الكتاب النقاب عن كيفية تحسين أداء الموظفين بالشركات بداية من كبار المسئولين وحتى أصغر الموظفين ويستعرض كيفية تصميم نظم تكنولوجيا المعلومات للاستجابة لمتطلبات السوق بشكل سريع وزيادة العائدات على استثمارات هذه التكنولوجيا في الوقت نفسه ويناقش بعض الطرق التي تضيف أبعادا أخرى لأساليب إعادة هيكلة العمل وذلك بهدف تحسين الجودة وتنفيذ العمليات التجارية على النحو الأمثل والتنمية المستمرة لمهارات الموظفين.
BOOK
The magnetic field and turbulence of the cosmic web measured using a brilliant fast radio burst
Fast radio bursts (FRBs) are millisecond-duration events thought to originate beyond the Milky Way galaxy. Uncertainty surrounding the burst sources, and their propagation through intervening plasma, has limited their use as cosmological probes. We report on a mildly dispersed (dispersion measure 266.5 ± 0.1 parsecs per cubic centimeter), exceptionally intense (120 ± 30 janskys), linearly polarized, scintillating burst (FRB 150807) that we directly localize to 9 square arc minutes. On the basis of a low Faraday rotation (12.0 ± 0.7 radians per square meter), we infer negligible magnetization in the circum-burst plasma and constrain the net magnetization of the cosmic web along this sightline to <21 nanogauss, parallel to the line-of-sight. The burst scintillation suggests weak turbulence in the ionized intergalactic medium.
Journal Article
Gravitational waves from binary supermassive black holes missing in pulsar observations
Gravitational waves are expected to be radiated by supermassive black hole binaries formed during galaxy mergers. A stochastic superposition of gravitational waves from all such binary systems would modulate the arrival times of pulses from radio pulsars. Using observations of millisecond pulsars obtained with the Parkes radio telescope, we constrained the characteristic amplitude of this background, Ac,yr, to be <1.0 × 10–15 with 95% confidence. This limit excludes predicted ranges for Ac,yr from current models with 91 to 99.7% probability. We conclude that binary evolution is either stalled or dramatically accelerated by galactic-center environments and that higher-cadence and shorter-wavelength observations would be more sensitive to gravitational waves.
Journal Article