Neurocognitive and Seizure Outcomes of Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy.

Objective. To report our institutional seizure and neuropsychological outcomes for a series of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH) between 2004 and 2011. Methods. A retrospective study of patients with mTLE was conducted. Seizure outcome was reported using time-to-event analysis. Cognitive outcome was reported using the change principal in component factor scores, one each, for intellectual abilities, visuospatial memory, and verbal memory. The Boston Naming Test was used for naming assessment. Language dominant and nondominant resections were compared separately. Student's t-test was used to assess statistical significance. Results. Ninety-six patients (75 ATL, 21 SelAH) were included; fifty-four had complete neuropsychological follow-up. Median follow-up was 40.5 months. There was no statistically significant difference in seizure freedom or any of the neuropsychological outcomes, although there was a trend toward greater postoperative decline in naming in the dominant hemisphere group following ATL. Conclusion. Seizure and neuropsychological outcomes did not differ for the two surgical approaches which is similar to most prior studies. Given the theoretical possibility of SelAH sparing language function in patients with epilepsy secondary to mesial temporal sclerosis and the limited high-quality evidence creating equipoise, a multicenter randomized clinical trial is warranted

Special Considerations in Facial Transplantation: A Systematic Review

Background: Vascularized composite allotransplantation (VCA) of the face is an exceedingly complex procedure, requiring extensive planning and surgical precision in order to successfully manage patients with facial disfigurements. This review aims to present an overview of the salient anatomic considerations in facial transplantation, as well as give attention to unique patient populations and special considerations. Methods: A literature review was performed in search of articles pertaining to considerations in facial transplantation using the databases PubMed, Web of Science, and Cochrane. Articles selected for further review included full-text articles with an emphasis on specific anatomic defects and how they were addressed in the transplant process, as well as management of special patient populations undergoing facial transplantation. Results: In total, 19 articles were deemed appropriate for inclusion. This systematic review of the literature pertaining to considerations in facial transplantation revealed common themes, as well as the importance of a multidisciplinary approach to the procedure. The ultimate outcome is dependent upon the synchronization of subunits of the allograft and the desired functional outcomes, including osseous, ocular, oral, and otologic considerations. Management of specific pathology and subgroups of patients are critical aspects. Although pediatric face transplantation has not yet been performed, it is likely a future step in the evolution of this procedure. Conclusion: When performing a face transplantation, many components must be considered pre-, intra-, and post-operatively. This systematic review presents specific anatomic considerations, as well as information about special patient populations within this cross-section of multidisciplinary microsurgery, psychiatry, and transplant immunology

On Nibbles and Bytes: The Conundrum of Memory for Space Systems - NASA Electronic Parts and Packaging (NEPP) and Efforts in Memories

Radiation requirements and trends. TID: 1) >90% of NASA applications are < 100 krads-Si in piecepart requirements. a) Many commercial devices (NVM and SDRAMs) meet or come close to this. b) Charge pump TID tolerance has improved an order magnitude over the last 10 years. 2) There are always a few programs with higher level needs and, of course, defense needs SEL: 1) Prefer none or rates that are considered low risk. a) Latent damage is a bear to deal with. 2) As we re packing cells tighter and even with lower Vdd, we re seeing SEL on commercial devices regularly (<90nm). a) Often in power conversion, I/O, or control areas. SEU: 1) It s not the bit errors, it s the SEFIs errors that are the biggest issues. a) Scrubbing concerns for risk, power, speed

Public attitudes towards alcohol control policies in Scotland and England: Results from a mixed-methods study

The harmful effects of heavy drinking on health have been widely reported, yet public opinion on governmental responsibility for alcohol control remains divided. This study examines UK public attitudes towards alcohol policies, identifies underlying dimensions that inform these, and relationships with perceived effectiveness. A cross-sectional mixed methods study involving a telephone survey of 3477 adult drinkers aged 16-65 and sixteen focus groups with 89 adult drinkers in Scotland and England was conducted between September 2012 and February 2013. Principal components analysis (PCA) was used to reduce twelve policy statements into underlying dimensions. These dimensions were used in linear regression models examining alcohol policy support by demographics, drinking behaviour and perceptions of UK drinking and government responsibility. Findings were supplemented with a thematic analysis of focus group transcripts. A majority of survey respondents supported all alcohol policies, although the level of support varied by type of policy. Greater enforcement of laws on under-age sales and more police patrolling the streets were strongly supported while support for pricing policies and restricting access to alcohol was more divided. PCA identified four main dimensions underlying support on policies: alcohol availability, provision of health information and treatment services, alcohol pricing, and greater law enforcement. Being female, older, a moderate drinker, and holding a belief that government should do more to reduce alcohol harms were associated with higher support on all policy dimensions. Focus group data revealed findings from the survey may have presented an overly positive level of support on all policies due to differences in perceived policy effectiveness. Perceived effectiveness can help inform underlying patterns of policy support and should be considered in conjunction with standard measures of support in future research on alcohol control policies

German ambulatory care physicians' perspectives on clinical guidelines – a national survey

BACKGROUND: There has been little systematic research about the extent to which German physicians accept or reject the concept and practice of a) clinical practice guidelines (CPG) and b) evidence based medicine (EBM) The aim of this study was to investigate German office-based physicians' perspective on CPGs and EBM and their application in medical practice. METHODS: Structured national telephone survey of ambulatory care physicians, four thematic blocks with 21 questions (5 point Likert scale). 511 office-based general practitioners and specialists. Main outcome measures were the application of Clinical Practice Guidelines in daily practice, preference for sources of guidelines and degree of knowledge and acceptance of EBM. In the data analysis Pearson's correlation coefficient was used for explorative analysis of correlations. The comparison of groups was performed by Student's t-test. Chi(2 )test was used to investigate distribution of two or more categorical variables. RESULTS: Of the total study population 55.3% of physicians reported already using guidelines in the treatment of patients. Physicians in group practices (GrP) as well as general practitioners (GP) agreed significantly more with the usefulness of guidelines as a basis for patient care than doctors in single practices (SP) or specialists (S) (Student's t-test mean GP 2.57, S 2.84, p < 0.01; mean GrP 2.55, SP 2.80, p < 0.05). 33.1% of the participants demonstrated a strong rejection to the application of guidelines in patient care. Acceptance of guidelines from a governmental institution was substantially lower than from physician networks or medical societies (36.2% vs. 53.4% vs. 62.0%). 73.8% of doctors interpret EBM as a combination of scientific research and individual medical knowledge; 80% regard EBM as the best basis for patient care. CONCLUSION: Despite a majority of physicians accepting and applying CPGs a large group remains that is critical and opposed to the utilization of CPGs in daily practice and to the concept of EBM in general. Doctors in single practice and specialists appear to be more critical than physicians in group practices and GPs. Future research is needed to evaluate the willingness to acquire necessary knowledge and skills for the promotion and routine application of CPGs

Cluster randomized trial assessing the effects of rapid ethical assessment on informed consent comprehension in a low-resource setting

Background Maximizing comprehension is a major challenge for informed consent processes in low-literacy and resource-limited settings. Application of rapid qualitative assessments to improve the informed consent process is increasingly considered useful. This study assessed the effects of Rapid Ethical Assessment (REA) on comprehension, retention and quality of the informed consent process. Methods A cluster randomized trial was conducted among participants of HPV sero-prevalence study in two districts of Northern Ethiopia, in 2013. A total of 300 study participants, 150 in the intervention and 150 in the control group, were included in the study. For the intervention group, the informed consent process was designed with further revisions based on REA findings. Informed consent comprehension levels and quality of the consent process were measured using the Modular Informed Consent Comprehension Assessment (MICCA) and Quality of Informed Consent (QuIC) process assessment tools, respectively. Result Study recruitment rates were 88.7 % and 80.7 % (p = 0.05), while study retention rates were 85.7 % and 70.3 % (p < 0.005) for the intervention and control groups respectively. Overall, the mean informed consent comprehension scores for the intervention and control groups were 73.1 % and 45.2 %, respectively, with a mean difference in comprehension score of 27.9 % (95 % CI 24.0 % - 33.4 %; p < 0.001,). Mean scores for quality of informed consent for the intervention and control groups were 89.1 % and 78.5 %, respectively, with a mean difference of 10.5 % (95 % CI 6.8 -14.2 %; p < 0.001). Conclusion Levels of informed consent comprehension, quality of the consent process, study recruitment and retention rates were significantly improved in the intervention group. We recommend REA as a potential modality to improve informed consent comprehension and quality of informed consent process in low resource settings

Aldose Reductase Inhibition Prevents Metaplasia of Airway Epithelial Cells

BACKGROUND: Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo. METHODOLOGY/FINDINGS: Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE. CONCLUSIONS: The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 &#215; 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 &#215; 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 &#215; 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers

South-returning wings: Yang Shih and the new Sung metaphysics.

The Neo-Confucian philosopher Yang Shih (1053-1135) flourished during one of the most fertile periods in the history of Chinese philosophy. His curiosity about differences among the Confucian classics, his interest in the Book of Change, his exploration of Buddhist philosophy and his reaction against the philosophical foundation of Wang An-shih's political policies mark Yang Shih as highly representative of his generation. That these factors led to his formulation of a Confucian metaphysics makes him philosophically significant. Further, as the Ch'eng brothers' emissary to southern China, the founder of the Tung-lin Academy, and a progenitor of Chu Hsi, Yang's historical significance is considerable. Yang Shih forms the link between northern and southern China, the Ch'eng brothers and Chu Hsi. This study offers two types of framework within which the diverse elements of Yang Shih's thought may be analyzed: (1) a systemic approach based on the centrality of metaphysics to his teachings, and (2) a comparative approach examining Yang's reaction to the philosophical underpinnings of Wang An-shih's political theories. The major portion of the dissertation deals with Yang's concept of the Tao as a palpable entity, its operator (the principle of change), and its dynamic (response). It examines the ramifications of this groundwork for Yang's theories of human nature and the value of wen (the written and cultural heritage) as well as his attitude toward so-called "heterodox" schools, most notably Buddhism and Taoism. The secondary portion of the dissertation focusses on Yang Shih's criticism of Wang An-shih's Tzu-shuo. Despite the marked divergence of their approaches to political and social issues, an examination of their respective philosophical theories shows the difference between Yang Shih and Wang An-shih to be predominantly one of discourse and emphasis rather than fundamental metaphysical theory. Three appendices follow the body of the dissertation. The first describes the various available editions of the primary source text; the second consists of a biography of Yang Shih; and a glossary of Chinese terms forms the third