Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
572
result(s) for
"Robson, Mark"
Sort by:
اللغة نظريا
جاء هذا الكتاب لمعالجة الاعتقاد الذي مفاده أن الباحثين في علم اللغة لا يميلون إلى معرفة ما يكفي عن فلسفة اللغة والنظريات النقدية المرتبطة باللغة، والاعتقاد بأن الباحثين في الفلسفة والنظرية النقدية كثيرا ما يتحدثون حول اللغة دون معرفة الكثير عن علم اللغة. كما تنطلق هذه الملاحظة، في الحقيقة، على العديد من زملائنا الأكاديميين، كما يمكن القول إنها تنطبق على مؤلفي هذا الكتاب قبل المباشرة بكتابته، وتعد كتابته بالنسبة لنا عملية تعلم قيمة، كما أنه قد يعد كتابا كان يتوجب كتابته بالاشتراك مع الآخرين. يهدف كتاب \"اللغة نظريا\" إلى التأمل في مقاربات مختلفة للغة، وتكفي الدلالات المتعددة التي تشير إليها كلمة (in) الخاصة بعنوان الكتاب (Language in Theory) لتذكيرنا بذلك أولا، يعنى الكتاب بالنظريات اللغوية، والأطر، والنماذج والمقاربات، عبر نطاق الأنظمة المعرفية التي انكبت سلسلة (RELI) برمتها على دراستها.
Book
Heavy metal contamination and human health risk assessment in drinking water from shallow groundwater wells in an agricultural area in Ubon Ratchathani province, Thailand
Most local people in the agricultural areas of Hua-ruea sub-district, Ubon Ratchathani province (Thailand), generally consume shallow groundwater from farm wells. This study aimed to assess the health risk related to heavy metal contamination in that groundwater. Samples were randomly collected from 12 wells twice in each of the rainy and the dry seasons and were analyzed by inductive coupled plasma spectrometry-mass spectrometry (ICP-MS). The concentration of detected metals in each well and the overall mean were below the acceptable groundwater standard limits for As, Cd, Cr, Cu, Hg, Ni and Zn, but Pb levels were higher in four wells with an overall average Pb concentration of 16.66 ± 18.52 μg/l. Exposure questionnaires, completed by face-to-face interviews with 100 local people who drink groundwater from farm wells, were used to evaluate the hazard quotients (HQs) and hazard indices (HIs). The HQs for non-carcinogenic risk for As, Cu, Zn and Pb, with a range of 0.004–2.901, 0.053–54.818, 0.003–6.399 and 0.007–26.80, respectively, and the HI values (range from 0.10 to 88.21) exceeded acceptable limits in 58 % of the wells. The HI results were higher than one for groundwater wells located in intensively cultivated chili fields. The highest cancer risk found was 2.6 × 10⁻⁶ for As in well no. 11. This study suggested that people living in warmer climates are more susceptible to and at greater risk of groundwater contamination because of their increased daily drinking water intake. This may lead to an increased number of cases of non-carcinogenic and carcinogenic health defects among local people exposed to heavy metals by drinking the groundwater.
Journal Article
The best horror of the year. Volume ten
A group of mountain climbers, caught in the dark, fights to survive their descent; An American band finds more than they bargained for in Mexico while scouting remote locations for a photo shoot; A young student's exploration into the origins of a mysterious song leads him on a winding, dangerous path through the US's deep south; A group of kids scaring each other with ghost stories discovers alarming consequences. The Best Horror of the Year showcases the previous year's best offerings in horror short fiction. This edition includes award-winning and critically acclaimed authors Mark Morris, Kaaron Warren, John Langan, Carole Johnstone, Brian Hodge, and others. For more than three decades, award-winning editor and anthologist Ellen Datlow has had her finger on the pulse of the latest and most terrifying in horror writing. Night Shade Books is proud to present the tenth volume in this annual series, a new collection of stories to keep you up at night.
BOOK
Points to Consider Regarding Risk-Reducing Mastectomy in High-, Moderate-, and Low-Penetrance Gene Carriers
Risk-reducing mastectomy is considered a safe and effective surgical procedure in high-risk individuals with BRCA1/2 germline mutations. Multigene panels identify women with alterations in breast cancer susceptibility genes other than BRCA1/2. International guidelines classify these genes as high-, moderate-, and low-penetrance based on their associated relative risk for breast cancer. Classification of specific genes is not always concordant among guidelines, and the indications for risk-reducing mastectomy are not defined. In this opinion paper, we review some considerations to clarify these controversial points.
Journal Article
Genome doubling shapes the evolution and prognosis of advanced cancers
Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospectively sequenced advanced cancer patients. WGD varied by tumor lineage and molecular subtype, and arose early in carcinogenesis after an antecedent transforming driver mutation. While associated with
TP53
mutations, 46% of all WGD arose in
TP53
-wild-type tumors and in such cases was associated with an E2F-mediated G1 arrest defect, although neither aberration was obligate in WGD tumors. The variability of WGD across cancer types can be explained in part by cancer cell proliferation rates. WGD predicted for increased morbidity across cancer types, including
KRAS
-mutant colorectal cancers and estrogen receptor-positive breast cancers, independently of established clinical prognostic factors. We conclude that WGD is highly common in cancer and is a macro-evolutionary event associated with poor prognosis across cancer types.
The authors identify whole-genome doubling (WGD) in 30% of ~10,000 sequenced tumors from patients with advanced cancer. WGD correlates with increased risk of death across cancer types.
Journal Article
Counselling framework for moderate-penetrance cancer-susceptibility mutations
The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice. The appropriate management of individuals harbouring moderate-penetrance genetic variants in individuals referred for clinical testing is unclear. The authors of this Perspectives article provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer.
The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice, particularly in the USA, despite concerns regarding the uncertain clinical validity for some gene variants and the uncertain clinical utility of most multigene panels. So-called 'moderate-penetrance' gene mutations associated with cancer susceptibility are identified in approximately 2–5% of individuals referred for clinical testing; some of these mutations are potentially actionable. Nevertheless, the appropriate management of individuals harbouring such moderate-penetrance genetic variants is unclear. The cancer risks associated with mutations in moderate-penetrance genes are lower and different than those reported for high-penetrance gene mutations (such as mutations in
BRCA1
and
BRCA2
, and those associated with Lynch syndrome). The extrapolation of guidelines for the management of individuals with high-penetrance variants of cancer-susceptibility genes to the clinical care of patients with moderate-penetrance gene mutations could result in substantial harm. Thus, we provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer.
Journal Article
Cancer therapy shapes the fitness landscape of clonal hematopoiesis
Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in
ASXL1
are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (
TP53
,
PPM1D
,
CHEK2
). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies.
Environmental exposures shape patterns of selection for mutations in clonal hematopoiesis. Cancer therapies promote the growth of clones with mutations that are strongly enriched in treatment-related myeloid neoplasms.
Journal Article
Tumour lineage shapes BRCA-mediated phenotypes
Mutations in
BRCA1
and
BRCA2
predispose individuals to certain cancers
1
–
3
, and disease-specific screening and preventative strategies have reduced cancer mortality in affected patients
4
,
5
. These classical tumour-suppressor genes have tumorigenic effects associated with somatic biallelic inactivation, although haploinsufficiency may also promote the formation and progression of tumours
6
,
7
. Moreover,
BRCA1/2
-mutant tumours are often deficient in the repair of double-stranded DNA breaks by homologous recombination
8
–
13
, and consequently exhibit increased therapeutic sensitivity to platinum-containing therapy and inhibitors of poly-(ADP-ribose)-polymerase (PARP)
14
,
15
. However, the phenotypic and therapeutic relevance of mutations in
BRCA1
or
BRCA2
remains poorly defined in most cancer types. Here we show that in the 2.7% and 1.8% of patients with advanced-stage cancer and germline pathogenic or somatic loss-of-function alterations in
BRCA1/2
, respectively, selective pressure for biallelic inactivation, zygosity-dependent phenotype penetrance, and sensitivity to PARP inhibition were observed only in tumour types associated with increased heritable cancer risk in
BRCA1/2
carriers (BRCA-associated cancer types). Conversely, among patients with non-BRCA-associated cancer types, most carriers of these
BRCA1/2
mutation types had evidence for tumour pathogenesis that was independent of mutant
BRCA1/2
. Overall, mutant BRCA is an indispensable founding event for some tumours, but in a considerable proportion of other cancers, it appears to be biologically neutral—a difference predominantly conditioned by tumour lineage—with implications for disease pathogenesis, screening, design of clinical trials and therapeutic decision-making.
Analysis of more than 17,000 tumours suggests that the contribution of germline and somatic mutations in the
BRCA1
and
BRCA2
genes to oncogenesis depends on tumour lineage.
Journal Article
High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants
Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2 megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA–white blood cell sequencing for accurate variant interpretation.
Journal Article
Management of an Inherited Predisposition to Breast Cancer
A healthy 33-year-old woman comes to establish care. She has no breast symptoms, her age at menarche was 14 years, and she has no children. She notes a family history of early-onset breast cancer in her sister, mother, and maternal aunt. Her maternal grandfather died of prostate cancer. What screening and risk-reduction strategies would you advise?
A healthy 33-year-old woman notes a family history of early-onset breast cancer in her sister, mother, and maternal aunt. What screening and risk-reduction strategies would you advise?
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
Stage
A healthy 33-year-old woman comes to establish care. She reports no breast symptoms, her age at menarche was 14, and she has no children. She notes a family history of early-onset breast cancer in her sister (whose condition was diagnosed at the age of 35 years and who is alive at 39 years), mother (diagnosed at 37 years and alive at 60 years), and maternal aunt (diagnosed at 42 years and alive at 62 years). Her maternal grandfather died of prostate cancer. What would you advise regarding screening for breast cancer and strategies to reduce her risk?
The Clinical . . .
Journal Article