Explore the vast range of titles available.

The use of data from the real world to address clinical and policy-relevant questions that cannot be answered using data from clinical trials is garnering increased interest. Indeed, data from cancer registries and linked treatment records can provide unique insights into patients, treatments and outcomes in routine oncology practice. In this Review, we explore the quality of real-world data (RWD), provide a framework for the use of RWD and draw attention to the methodological pitfalls inherent to using RWD in studies of comparative effectiveness. Randomized controlled trials and RWD remain complementary forms of medical evidence; studies using RWD should not be used as substitutes for clinical trials. The comparison of outcomes between nonrandomized groups of patients who have received different treatments in routine practice remains problematic. Accordingly, comparative effectiveness studies need to be designed and interpreted very carefully. With due diligence, RWD can be used to identify and close gaps in health care, offering the potential for short-term improvement in health-care systems by enabling them to achieve the achievable.In the past few years, the use of data from the real world has garnered increasing interest; however, studies using real-world data (RWD) should not be used as substitutes for clinical trials. The authors of this Review explore the quality of RWD, provide a framework for the use of RWD and draw attention to the methodological pitfalls inherent to using RWD.

الكتاب يهدف لتوفير رؤية مبدئية عن كيفية البحث، من عملية اختيار الموضوع وجمع المعلومات والمصادر إلى عملية الكتابة للنتائج، يغطي هذا الكتاب كل ما يتعلق بالبحث العلمي من إعداد وتخطيط وكتابة وإخراج ونشر وهو موجه للباحثين في شتى العلوم بشكل عام من طلاب وأساتذة وموظفين ويحاول المؤلفون على نحو خاص طرح حلول للمعضلات التي تواجه طلاب الدراسات العليا والباحثين (وكثير منهم قد لا يجيد تحدث اللغة الإنجليزية) ومن هذه المشاكل، عملية جمع المعلومات والتحقق منها وتوثيقها والكتابة عنها ويتناول هذا الكتاب مهمة البحث عن مجرد الفكرة، وكيفية صياغتها والبحث عن المشكلة وكيفية النشر في المجلات العلمية وقواعده كما يتطرق المؤلفون أيضا لتنوع أساليب الكتابة وأنواع المصادر وكيف يتم توظيف كل منها وفي أي مرحلة من البحث.

AbstractObjectiveTo quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.DesignSystematic review and meta-analysis.Data sourcesPublished studies in Medline from 1 January 2000 to 10 April 2020.Eligibility criteria for selecting studiesCurative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.ResultsThe review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.ConclusionsCancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

\"This new edition of the classic reference work on writing research papers recognizes recent developments in information literacy--including finding, evaluating, and citing a wide range of digital sources--and the evolving use of software for citation management, graphics, and paper format and submission while continuing to reflect best practices for research and writing, as adapted from the most recent editions of The Craft of Research and The Chicago Manual of Style\"--Provided by publisher.

Crumb rubber granulate (CRG) produced from end of life tires (ELTs) is commonly applied to synthetic turf pitches (STPs), playgrounds, safety surfaces and walkways. In addition to fillers, stabilizers, cross-linking agents and secondary components (e.g., pigments, oils, resins), ELTs contain a range of other organic compound and heavy metal additives. While previous environmental impact studies on CRG have focused on terrestrial soil and freshwater ecosystems, many sites applying CRG in Norway are coastal. The current study investigated the organic chemical and metal additive content of ‘pristine’ and ‘weathered’ CRG and their seawater leachates, as well as uptake and effects of leachate exposure using marine copepods (Acartia and Calanus sp.). A combination of pyrolysis gas chromatography mass spectrometry (py-GC-MS) and chemical extraction followed by GC-MS analysis revealed similar organic chemical profiles for pristine and weathered CRG, including additives such as benzothiazole, N-1,3-dimethylbutyl-N′-phenyl-p-phenylenediamine and a range of polycyclic aromatic hydrocarbons (PAHs) and phenolic compounds (e.g., bisphenols). ICP-MS analysis revealed g kg–1 quantities of Zn and mg kg–1 quantities of Fe, Mn, Cu, Co, Cr, Pb, and Ni in the CRG. A cocktail of organic additives and metals readily leached from the CRG into seawater, with the most abundant leachate components being benzothiazole and Zn, Fe, Co (metals), as well as detectable levels of PAHs and phenolic compounds. Concentrations of individual components varied with CRG source material and CRG to seawater ratio, but benzothiazole and Zn were typically the organic and metal components present at the highest concentrations in the leachates. While organic chemical concentrations in the leachates stabilized within days, metals continued to leach out over the 30-day period. Marine copepods exposed to high CRG leachate concentrations exhibited high mortalities within 48 h. The smaller lipid-poor Acartia had a higher sensitivity to leachates than the larger lipid-rich Calanus, indicating species-specific differences in vulnerability to leachates. The effect on survival was alleviated at lower leachate concentrations, indicating a dose-response relationship. Benzothiazole and its derivatives appear to be of concern owing to their proven toxicity, while bisphenols are also known to be toxic and were enriched in the leachates relative to the other compounds in the CRG.

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public. Radical rethinking is needed to address the burning issues in cancer care in low- and middle-income countries. In this Perspective, the authors outline the main challenges and top priorities for cancer research now and into the future.

Plastic garbage patches at the ocean surface are symptomatic of a wider pollution affecting the whole marine environment. Sinking of plastic debris increasingly appears to be an important process in the global fate of plastic in the ocean. However, there is insufficient knowledge about the processes affecting plastic distributions and degradation and how this influences the release of additives under varying environmental conditions, especially in deep-sea environments. Here we show that in abiotic conditions increasing hydrostatic pressure inhibits the leaching of the heaviest organic additives such as tris(2-ethylhexyl) phosphate and diisononyl phthalate from polyethylene and polyvinylchloride materials, whereas deep-sea and surface marine prokaryotes promote the release of all targeted additives (phthalates, bisphenols, organophosphate esters). This study provides empirical evidences for more efficient additive release at the ocean surface than in deep seawater, where the major plastic burden is supposed to transit through before reaching the sediment compartment. Plastics are major marine pollutants, and while research suggests that they can release potential harmful additives into seawater, how environmental conditions influence this is unknown. Here the authors determine that byproducts released from microplastics are less under deep-sea conditions versus surface.

The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice. This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries. 87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 [17%] in low-income and lower-middle-income countries, 165 [17%] in upper-middle-income countries, and 618 [65%] in high-income countries). The most commonly selected medicines were doxorubicin (by 499 [53%] of 948 respondents), cisplatin (by 470 [50%]), paclitaxel (by 423 [45%]), pembrolizumab (by 414 [44%]), trastuzumab (by 402 [42%]), carboplatin (by 390 [41%]), and 5-fluorouracil (by 386 [41%]). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9–54% in low-income and lower-middle-income countries, 13–90% in upper-middle-income countries, and 68–94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13–68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2–41% of respondents in upper-middle-income countries and 0–9% in high-income countries. These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines. None.

The addition of water on or below the earth’s surface generates changes in stress that can trigger both stable and unstable sliding of landslides and faults. While these sliding behaviours are well-described by commonly used mechanical models developed from laboratory testing (e.g., critical-state soil mechanics and rate-and-state friction), less is known about the field-scale environmental conditions or kinematic behaviours that occur during the transition from stable to unstable sliding. Here we use radar interferometry (InSAR) and a simple 1D hydrological model to characterize 8 years of stable sliding of the Mud Creek landslide, California, USA, prior to its rapid acceleration and catastrophic failure on May 20, 2017. Our results suggest a large increase in pore-fluid pressure occurred during a shift from historic drought to record rainfall that triggered a large increase in velocity and drove slip localization, overcoming the stabilizing mechanisms that had previously inhibited landslide acceleration. Given the predicted increase in precipitation extremes with a warming climate, we expect it to become more common for landslides to transition from stable to unstable motion, and therefore a better assessment of this destabilization process is required to prevent loss of life and infrastructure.