Medical Research and Incompetent Adults

The spectre of Nazi medical experimentation during the Second World War undoubtedly hangs over any discussion of medical research and incompetent adults. The concentration camp experiments denied the rights of people who would have been able to give or withhold consent but were, of course, not asked. The fears raised by the nature of these experiments has given rise to a real, understandable and genuine concern that research participants, particularly those who are vulnerable, may be abused through their participation. For example, Professors Kennedy and Grubb take the view that nontherapeutic research on incompetent adults is prohibited and go on to say that “given the history of Europe in the 1930s and 1940s which culminated in the Nuremberg Trials ... it is entirely understandable that some European countries would hold the view that an absolute prohibition was the only defensible [position].” The question that arises is whether prohibition is always the correct approach, or whether some forms of research should be permissible, recognising that strict protections will be necessary. We reflect upon the rigidity of the distinction between therapeutic and non-therapeutic research in the context of a research project that we undertook

Adverse effects of perinatal nicotine exposure on reproductive outcomes

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women

Optimal Location of Sources in Transportation Networks

We consider the problem of optimizing the locations of source nodes in transportation networks. A reduction of the fraction of surplus nodes induces a glassy transition. In contrast to most constraint satisfaction problems involving discrete variables, our problem involves continuous variables which lead to cavity fields in the form of functions. The one-step replica symmetry breaking (1RSB) solution involves solving a stable distribution of functionals, which is in general infeasible. In this paper, we obtain small closed sets of functional cavity fields and demonstrate how functional recursions are converted to simple recursions of probabilities, which make the 1RSB solution feasible. The physical results in the replica symmetric (RS) and the 1RSB frameworks are thus derived and the stability of the RS and 1RSB solutions are examined.Comment: 38 pages, 18 figure

Demographic trends in the incidence of malignant appendiceal tumours in England between 1995 and 2016:Population-based analysis

AIMS: Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors. METHODS: All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis. RESULTS: A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20–29 years (15.6 per cent, 95 per cent c.i 12.7–18.6 per cent) and 30–39 years (14.2 per cent, 12.2–16.2 per cent) and lowest among those aged 70–79 years (6.8 per cent, 5.7–8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003. CONCLUSIONS: The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems

HST morphologies of local Lyman break galaxy analogs I: Evidence for starbursts triggered by merging

Heckman et al. (2005) used the Galaxy Evolution Explorer (GALEX) UV imaging survey to show that there exists a rare population of nearby compact UV-luminous galaxies (UVLGs) that closely resembles high redshift Lyman break galaxies (LBGs). We present HST images in the UV, optical, and Ha, and resimulate them at the depth and resolution of the GOODS/UDF fields to show that the morphologies of UVLGs are also similar to those of LBGs. Our sample of 8 LBG analogs thus provides detailed insight into the connection between star formation and LBG morphology. Faint tidal features or companions can be seen in all of the rest-frame optical images, suggesting that the starbursts are the result of a merger or interaction. The UV/optical light is dominated by unresolved (~100-300 pc) super starburst regions (SSBs). A detailed comparison with the galaxies Haro 11 and VV 114 at z=0.02 indicates that the SSBs themselves consist of diffuse stars and (super) star clusters. The structural features revealed by the new HST images occur on very small physical scales and are thus not detectable in images of high redshift LBGs, except in a few cases where they are magnified by gravitational lensing. We propose, therefore, that LBGs are mergers of gas-rich, relatively low-mass (~10^10 Msun) systems, and that the mergers trigger the formation of SSBs. If galaxies at high redshifts are dominated by SSBs, then the faint end slope of the luminosity function is predicted to have slope alpha~2. Our results are the most direct confirmation to date of models that predict that the main mode of star formation in the early universe was highly collisional.Comment: 32 pages, 15 figures. ApJ In pres

Extrapleural pneumonectomy for malignant pleural mesothelioma: Outcomes of treatment and prognostic factors

ObjectiveThis study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma.MethodsFrom October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy.ResultsThe mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses.ConclusionThe present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma

Dissociation cross sections of ground-state and excited charmonia with light mesons in the quark model

We present numerical results for the dissociation cross sections of ground-state, orbitally- and radially-excited charmonia in collisions with light mesons. Our results are derived using the nonrelativistic quark model, so all parameters are determined by fits to the experimental meson spectrum. Examples of dissociation into both exclusive and inclusive final states are considered. The dissociation cross sections of several C=(+) charmonia may be of considerable importance for the study of heavy ion collisions, since these states are expected to be produced more copiously than the J/psi. The relative importance of the productions of ground-state and orbitally-excited charmed mesons in a pion-charmonium collision is demonstrated through the $\sqrt {s}$-dependent charmonium dissociation cross sections.Comment: 9 pages, 8 figure

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Multi-scale modeling study of the source contributions to near-surface ozone and sulfur oxides levels over California during the ARCTAS-CARB period

Chronic high surface ozone (O3) levels and the increasing sulfur oxides (SOx = SO2+SO4) ambient concentrations over South Coast (SC) and other areas of California (CA) are affected by both local emissions and long-range transport. In this paper, multi-scale tracer, full-chemistry and adjoint simulations using the STEM atmospheric chemistry model are conducted to assess the contribution of local emission sourcesto SC O3 and to evaluate the impacts of transported sulfur and local emissions on the SC sulfur budgetduring the ARCTAS-CARB experiment period in 2008. Sensitivity simulations quantify contributions of biogenic and fire emissions to SC O3 levels. California biogenic and fire emissions contribute 3–4 ppb to near-surface O3 over SC, with larger contributions to other regions in CA. During a long-range transport event from Asia starting from 22 June, high SOx levels (up to ~0.7 ppb of SO2 and ~1.3 ppb of SO4) is observed above ~6 km, but they did not affect CA surface air quality. The elevated SOx observed at 1–4 km is estimated to enhance surface SOx over SC by ~0.25 ppb (upper limit) on ~24 June. The near-surface SOx levels over SC during the flight week are attributed mostly to local emissions. Two anthropogenic SOx emission inventories (EIs) from the California Air Resources Board (CARB) and the US Environmental Protection Agency (EPA) are compared and applied in 60 km and 12 km chemical transport simulations, and the results are compared withobservations. The CARB EI shows improvements over the National Emission Inventory (NEI) by EPA, but generally underestimates surface SC SOx by about a factor of two. Adjoint sensitivity analysis indicated that SO2 levels at 00:00 UTC (17:00 local time) at six SC surface sites were influenced by previous day maritime emissions over the ocean, the terrestrial emissions over nearby urban areas, and by transported SO2 from the north through both terrestrial and maritime areas. Overall maritime emissions contribute 10–70% of SO2 and 20–60% fine SO4 on-shore and over the most terrestrial areas, with contributions decreasing with in-land distance from the coast. Maritime emissions also modify the photochemical environment, shifting O3 production over coastal SC to more VOC-limited conditions. These suggest an important role for shipping emission controls in reducing fine particle and O3concentrations in SC