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The current version of the Declaration of Helsinki states that ‘the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention(s) … ’. This wording implies that it is acceptable for patients to be assigned to receive an unproven new intervention and to be denied a best current proven intervention. We assert that patients being invited to participate in controlled trials cannot, ethically, be expected to forego proven beneficial forms of care. Patients being treated in controlled trials should not knowingly be disadvantaged compared with similar patients being treated in usual clinical care, where they have access to beneficial care. In this article, we have tried to separate for discussion ‘the withholding of effective care from trial participants’, ‘informed consent to treatment’, ‘blinding’ and ‘use of placebos’.

To assess the prevalence of abortion among population groups and changes in rates between 2008 and 2014.We used secondary data from the Abortion Patient Survey, the American Community Survey, and the National Survey of Family Growth to estimate abortion rates. We used information from the Abortion Patient Survey to estimate the lifetime incidence of abortion.Between 2008 and 2014, the abortion rate declined 25%, from 19.4 to 14.6 per 1000 women aged 15 to 44 years. The abortion rate for adolescents aged 15 to 19 years declined 46%, the largest of any group. Abortion rates declined for all racial and ethnic groups but were larger for non-White women than for non-Hispanic White women. Although the abortion rate decreased 26% for women with incomes less than 100% of the federal poverty level, this population had the highest abortion rate of all the groups examined: 36.6. If the 2014 age-specific abortion rates prevail, 24% of women aged 15 to 44 years in that year will have an abortion by age 45 years.The decline in abortion was not uniform across all population groups.

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It is stressed that the positive performance of small to medium sized enterprises (SMEs) is integral for the growth and advancements of regional, national and world economies. In spite of this, the performance of SMEs within specific regions is often varied with some regions outperforming others. The Northwest of England is traditionally a low performing region that has been starved of funding and job creation, often halting its overall contribution to the UK economy. However, the region is experiencing a resurge in its level of entrepreneurial spirit, enterprise creation, and sits behind the West Midlands and London only, in terms of SME birth rates. Worryingly, however, it possesses the second highest death rate of all UK regions with no logical or clear explanation for this issue. Yet, there is a severe lack of literature that provides regional focus on high potential and high performing regions such as the Northwest of England. Critical success factors (CSFs) are a long-established mechanism for monitoring and sustaining the performance of an enterprise. They have long been identified as a key part of strategizing towards success in business management. The identification of such factors is crucial to aid understanding and to help facilitate the survival and positive performance of SMEs. Therefore, this research will seek to address a literature gap and investigate success factors that are critical to success for North-western SMEs. An extensive literature review was firstly undertaken, revealing a large abundance of factors mentioned in the literature. Crucially, the literature revealed the ever-present issue of heterogeneity that impacts the accuracy of concluding whether a factor is of critical nature in varying contexts. The issue of heterogeneity is consistently highlighted as a problem, yet the homogenous term ‘SME’ continues to be applied with the assumption that critical success factors are of equal importance for all SME sizes. Therefore, a further research gap was identified. This being, does heterogeneity influence the level of criticalness when considering the three different sized businesses (micro, small and medium) included in the homogenous term SME. For this research, a post-positivist philosophy was adopted with an abductive approach. A mixed-method approach was employed, firstly conducting a critical literature review to unearth the CSFs that are repeatedly mentioned in related literature. Secondly, semi-structured interviews were utilised to gain the expert opinion as to whether the critical success factors discovered in the literature were of a critical nature to the Northwest of England, and to uncover the mechanics behind why the factor is regarded as critical. NVIVO 12 was employed to assist the analysis of qualitative data and 26 factors were confirmed as critical to success with 116 subthemes being discovered as to the reasons why they are considered critical. Following this, a self-administrated survey was created and distributed to SME owners registered in the Northwest of England with 207 surveys being received and valid for usage. SPSS 27 was employed in the analysis of the demographic statistics, along with the analysis techniques employed to generate interfernal statistics to satisfy the research aim, questions, and objectives. The quantitative findings discovered that 23 of the 26 factors were considered critical to success for micro sized businesses, 25 of the 26 were deemed critical for small sized businesses and 25 of the 26 were deemed critical for medium sized businesses. Additionally, the One-way ANOVA and post-hoc tests revealed that 8 of the 26 factors possessed a statistically significant difference. The Pearson correlation results revealed a host of varying correlations that differed greatly when comparing the sized businesses.

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Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

Objective: To demonstrate sexual dimorphism in serum leptin levels not only during puberty, but also in childhood in Japan. Design: Cross-sectional study. Setting: Hamamatsu-Hokuen study in Japan. Subjects: Body weight and height were measured in normal-weight Japanese children and adolescents (143 boys, 178 girls), and 161 boys and 129 girls whose percentage of overweight for the standard (%Wt) was more than+25%. Serum leptin levels were compared with %Wt. Subjects were divided into group 1 (6–10 y of age) and group 2 (11–15 y of age) according to their age. Results: In overweight subjects, leptin was more highly correlated with %Wt in boys of group 2 (r=0.67, P

Sex differences are commonly observed in behaviors that are closely linked to adaptive function, but sex differences can also be observed in behavioral "building blocks" such as locomotor activity and reward processing. Modern neuroscientific inquiry, in pursuit of generalizable principles of functioning across sexes, has often ignored these more subtle sex differences in behavioral building blocks that may result from differences in these behavioral building blocks. A frequent assumption is that there is a default (often male) way to perform a behavior. This approach misses fundamental drivers of individual variability within and between sexes. Incomplete behavioral descriptions of both sexes can lead to an overreliance on reduced "single-variable" readouts of complex behaviors, the design of which may be based on male-biased samples. Here, we advocate that the incorporation of new machine-learning tools for collecting and analyzing multimodal "big behavior" data allows for a more holistic and richer approach to the quantification of behavior in both sexes. These new tools make behavioral description more robust and replicable across laboratories and species, and may open up new lines of neuroscientific inquiry by facilitating the discovery of novel behavioral states. Having more accurate measures of behavioral diversity in males and females could serve as a hypothesis generator for where and when we should look in the brain for meaningful neural differences.

OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of −40.7% (95% confidence interval [CI]: −47.7 to −33.7) in A&E attendances, −25.8% (95% CI: −31.1 to −20.4) in emergency hospital admissions and −60.9% (95% CI: −66.1 to −55.7) in planned hospital admissions, in comparison to the 2018–2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.

Aims: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). Background: Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. Objectives: Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity and associated functional impairments. Methods: Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. Results: We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology’s within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. Conclusion: Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

China is the most productive seaweed farming country in the world and her seaweed imports and exports have a significant impact on global seaweed trade commodities and food security. Nevertheless, few studies had delved into the main characteristics and development of China's seaweed farming industry. This paper aims to narrow this research gap by analyzing trade patterns in China's seaweed products and the international competitiveness of seaweed product by using the international market share index (IMS), the trade competitiveness index (TC), and revealed comparative advantage index (RCA) from 2002 to 2017. The results showed that Japan, the Association of Southeast Asian Nations (ASEAN), Chile, Peru, and the Republic of Korea are China's main trade partners, the total trade value of China's seaweed products has grown rapidly, its imports have gradually exceeded exports, the trade deficit continues to expand, and its competitiveness keeps decreasing. The reasons for this trend may include the changing seaweed trade commodity structure, product differentiation, increased government support in competing countries, and trade barriers among the trade partners. We propose actively expanding international trade markets, establishing a strong seaweed product processing industry to develop high value-added seaweed products, optimizing the trade commodity structure, and differentiating of seaweed products to improve the competitiveness of China's seaweed products.

Using a continuous-time model of litigation, we show that the increasingly popular practice of third-party litigation financing has ambiguous welfare implications. A defendant and a plaintiff bargain over a settlement payment. The defendant takes costly actions to avoid deadweight losses associated with large transfers to the plaintiff. Litigation financing bolsters the plaintiff, leading to larger deadweight losses. However, by endogenously deterring the defendant from taking costly actions, litigation financing can nonetheless improve the joint surplus of the plaintiff and the defendant. In contrast to popular opinion, litigation financing does not necessarily encourage high-risk frivolous lawsuits.

Given the alleged uniqueness of Islamic stocks, it is expected that they should provide insurance when faced with adverse market conditions. This expectation is tested by assessing contagion, using 25 Islamic indexes during the period 2007–2017, by employing contemporary econometric techniques. The results reveal robust contagion effects of the financial crisis on Islamic stock indexes. Furthermore, we find Baker and Wurgler’s investor sentiment can predict Islamic stock returns during the crisis period. Our findings indicate that Islamic stocks cannot be used as a haven asset during financial turmoil.

Shariah screening discards the firms that belong to impermissible business sectors (or sin industries) and follow capital structure with high debt and current assets. This study tests whether the firms passing Shariah screening have better (or worse) governance quality as compared to firms not subjected to Islamic screening. The screened firms may have lesser governance quality as they cannot use debt to discipline managers or achieve optimal capital structure. On the contrary, they may be better governed as these firms get higher presence of institutional investors and better analyst coverage. This paper provides comparison of governance quality of Shariah compliant (SC) firms in United States by using proprietary dataset of Dow Jones US Indices. The screened firms offer ground for a natural experiment as they pass negative ethical screening and meet financial criteria for the inclusion in the index. The findings suggest that the SC firms have lesser governance quality than Shariah Non-Compliant firms. The lower level of governance can be attributed to lower Size, lower Profitability, higher Dividend Payout, higher Total Risk and lower Free Cash Flow. Various robustness tests are performed to validate the findings and the results remained robust. These findings provide useful insights about the governance mechanism of SC firms that are emerging as an important alternative investment class in the last two decades.

Cultural dimensions have a significant impact on capital structure decisions, particularly in Islamic economies where unique personal, social and ethical values are closely integrated with culture. This study considers the relationship between four Hofstede cultural dimensions to explain their connection with the capital structure decisions of Shariah-compliant firms. Using a panel of 342 Shariah complaint companies from Malaysia, Saudi Arabia and Pakistan for the period 2013 to 2017, this study investigates the influence of cultural dimensions on short-term, long-term and total leverage in the presence of several firm- and country-specific variables. On average, Saudi Arabian firms witnessed comparatively higher percentages of all three debt classifications considered. Typically, determinants of debt do not otherwise differ significantly across the three countries. Firms also carefully consider asset structure and growth opportunities when raising debt capital. On the other hand, when tested alongside cultural dimensions, Islamic firms from countries with (a) higher power distance scores, (b) higher levels of individualism, (c) higher masculinity scores and (d) lower degrees of uncertainty avoidance exhibit a preference for long-term debt. This finding diverges from the existing literature on non-Islamic firms. Agency theory and pecking order theory predominate in explaining our findings.

Traditionally, equity mispricing has been documented as an important determinant of speed of adjustment to target leverage levels. More recently, the impact of Shari’ah compliance has been shown to significantly affect capital structure decisions. In this paper, we explore the effect of equity mispricing in Shari’ah compliant (vs. non-compliant) firms. We conduct our study on a comprehensive sample of Malaysian firms from year 1998–2016. We show that established findings in the dynamic trade-off theory do not hold for Shari’ah compliant firms. Shari’ah compliant firms increase their reliance on equity financing at greater levels than non-compliant firms when they are above target levels and equities are overpriced. In contrast, for Shari’ah compliant firms below target levels and where equity is under-priced, the rate of adjustment is slower than non-compliant firms. Our findings suggest that managers of Shari’ah compliant firms are inclined to time the equity market when above target levels to capture the impact of lower costs of equity during periods of over-valuation of equity. However, those managers tend to be reluctant to resort to debt financing when below target leverage even in the presence of equity under-pricing.

This paper analyses the effect of bank lending and fee income on Islamic and conventional bank's performance. The paper builds a theoretical model and provides empirical evidence to show that Islamic banks as compared to conventional banks can have a greater reliance on fee-based income than returns from loans to increase their profitability. Using data from a sample of 20 countries for the period from 2000 to 2015 for Islamic and conventional banks, we find that the bank fee is an important determinant of the profitability of an Islamic bank. Interestingly, many commonly used measures such as loan to deposit ratio do not affect the Islamic banks' profitability as much as they do for conventional banks. Our findings imply that Islamic banks' lower sensitivity to loan to deposit ratio may contribute to lower credit risk. However, an over-reliance on fee-based income may affect their growth, profitability and sustainability in the long run.

Mediterranean mussel farming in Greece developed considerably during the last 40 years reaching a gross commodity product up to the limits of the country's production capacity (35–40,000 tonnes/year). Despite the achievements in the sector's growth, little or no effort has been attributed yet to risk assessment and moreover to risk management of the activity. The present effort aims at developing a working framework for the shellfish aquaculture of Greece to be used as a tool by the sector's decision makers to advance strategies for risk elimination or avoidance. The work was based on a generic risk management standard tool, the Joint Australian and New Zealand Risk Management Standard AS/NZS ISO 31000:2009 that has been adapted to the specific national characteristics of all levels of the mussel farming business -activities and the industry function. The framework supported by data sets regarding development, production, profits and losses, retrieved by surveys through distributed questionnaires or interviews during site-visits, as well as by collecting data from national and international authorities. Data input covered technology, farm size, farmer risk-attitude, risk-management strategies, risk-perceptions and socioeconomic profiles. Major risks and risk management options were identified providing aid for remediation risk policies to the stakeholders.

To overcome the cost of competition resulting from close social proximity while foraging in a group, individuals may balance their use of private (i.e. acquired from personal sampling) and social (i.e. acquired by watching other individuals) information in order to adjust their foraging strategy accordingly. Reliability of private information about environmental characteristics, such as the spatial distribution of prey, is thus likely to affect individual movement and social interactions during foraging. Our aim was to investigate how movement characteristics of foraging individuals changed as they acquired reliable private information about the spatial occurrence of prey in a foraging context. We allowed guppies (Poecilia reticulata) to develop the reliability of their private knowledge about prey spatial occurrence by repeatedly testing shoals in a foraging task under three experimental distributions of prey: 1) aggregated prey forming three patches located in fixed locations, 2) scattered distribution of prey with random locations, or 3) no prey (used as control). We then applied tracking methods to obtain individual time series of spatial coordinates from which we computed a suite of movement variables reflecting search effort, social proximity and locomotion characteristics during foraging, in order to examine changes occurring over repeated trials and to investigate which best explained foraging success. We show that foraging shoals became more efficient at finding and consuming food over the first three days by increasing their time spent active. Over time, individuals foraging on either scattered or aggregated prey travelled greater distances, showed an increasing distance to their closest neighbour and became slightly more stochastic in their acceleration profile, compared to control individuals. We found that behaviour changed as private information increased over time. Social proximity was the major predictor of foraging success in the absence of prior foraging information, while stochasticity in acceleration and search effort became the most important predictors of foraging success as information increased. In conclusion, we show that individual movement patterns changed as they acquire private information. Contrary to our predictions, the spatial distribution of prey did not affect any of the movement variables of interest. Our results emphasise the importance of information, both private and social, in shaping movement behaviour in animals. Keywords: social foraging, movement, private information, prey spatial distribution, fish.

There is a continuing interest in exploring the impact of operational excellence (OE) on operational performance. Several OE practices such as Lean, Agile, and Six Sigma are well recognized. However, not all OE deployments in firms have been successful, and a failure of such efforts has often been expensive. Past research reveals several critical failure factors (CFFs) that lead to OE deployment failures in firms. We present these CFFs as an integrated model, based on two dominant schools of OE that promote technical and behavioral factors independently. Further, we validate their direct and mediating relationships through an empirical examination of 663 responses collected from 153 manufacturing units across the USA, U.K., China, and India. This article contributes to the OE body of knowledge by examining the significant direct and mediating effects of behavioral and technical CFFs on the OE failures. Our findings reveal that the technical CFFs mediate the impact of behavioral CFFs on OE failures. Consequently, several managerial and theoretical implications are presented.

Summarization: Alternative tourism has gained considerable interest among consumers and enterprises in the tourism sector, creating new opportunities for providing high quality and innovative tourist services, while contributing to sustainable development. The Internet plays a key role as a tool for promoting alternative tourism. Motivated by this, this article presents an original research on the evaluation of the content features of the websites of enterprises involved with alternative tourism services in the region of Chania, Greece. The sample consists of 28 websites evaluated over 11 performance criteria through the ELECTRE III multicriteria method. The websites are ranked in a benchmarking context and the results of the evaluation are used to identify the most successful practices, as well as the website features that require improvements for the enterprises to take advantage of the opportunities that arise in the new era of technological innovation in the tourism sector. Presented on: IEEE Transactions on Engineering Management

Purpose To describe the use of glycerine in improving media clarity in cases with edematous cornea. Methods Retrospective case-series including patients with posterior segment pathologies needing surgical invention and having corneal edema. Each case was studied for the role of topical application of glycerine instead of viscoelastic agents and the course of surgery. The cases were followed up for minimum 3-months duration. Results Six cases with corneal edema having posterior segment pathology underwent surgery with intraoperative topical application of glycerine. The corneal edema was seen to clear with progression of surgery and was maintained until the end of surgery. Procedures like vitreoretinal surgery, identification of break, internal limiting membrane peeling, intraocular lens explantation, scleral indentation, DSEK graft removal, and subretinal band removal could be performed in these cases. Conclusion Intraoperative glycerine use during vitreoretinal surgeries is helpful in improving the corneal clarity and maintaining it till the end of surgery.

Diagnostic theories are fundamental to information system (IS) practice and are represented as trees. While there are approaches for validating diagnostic trees, these validate the overall performance of the tree rather than identifying ways incorrect diagnoses can occur. It is important to fully validate diagnostic trees because even if the tree gives the correct decision “most of the time,” it is possible for incorrect decisions traveling down little-used branches of the tree to result in catastrophic decisions. In this article, we describe the process of using a variant of q-sorting to validate diagnostic trees. In this methodology, diagnostic trees that independent experts develop are transformed into a quantitative form, and that quantitative form is tested to determine the inter-rater reliability of the individual branches in the tree. The trees are then successively transformed to incrementally test if they branch in the same way. The results help researchers not only identify quality items for use in a diagnostic tree but also facilitate diagnoses of problems with those items and facilitate the reconciliation of discrepant trees by experts. The methodology validates not only the whole tree but also its subparts.