The association of posttraumatic stress disorder with fast food and soda consumption and unhealthy weight loss behaviors among young women.
This study examines the association of posttraumatic stress disorder (PTSD) symptoms with fast food and soda consumption, unhealthy dieting behaviors, and body mass index (BMI) in a group of young women. This study was conducted on cross-sectional data gathered from 3181 females 16-24 years of age attending five publicly funded clinics in Texas. The associations among PTSD, fast food consumption frequency, soda consumption frequency, unhealthy dieting behaviors, and BMI were examined using binary and ordinal logistic regression. PTSD symptoms were associated with an increased frequency of consumption of fast food and soda as well as unhealthy dieting behaviors but not with increased body mass index (BMI). PTSD symptoms adversely affect both eating and dieting behaviors of young women. These behaviors may have negative long-term consequences for the health of females with PTSD symptoms.


Innovation, centralization, and growth. Coronary artery bypass graft surgery in Manitoba.
Innovation and diffusion of new surgical procedures are limited in Manitoba, Canada by restrictions on which hospitals are allowed to perform particular surgical programs. Programs centralizing performance of certain operations in a few hospitals have the potential for controlling costs and quality of care but may limit access for individuals living in other areas. Such issues are highlighted in this analysis of coronary artery bypass graft surgery in Manitoba. Patterns of growth and access are first examined; then regional variations in rates of bypass surgery are compared with rates for coronary angiography and valve surgery. Physician reluctance to refer patients to Winnipeg appears to be responsible for the lower rates of these procedures in Western Manitoba. The implications for studies of centralization/regionalization of medical services, physician decision-making, and diffusion of technology are explored.


Genetic deletion of glycogen synthase kinase-3beta abrogates activation of IkappaBalpha kinase, JNK, Akt, and p44/p42 MAPK but potentiates apoptosis induced by tumor necrosis factor.
Glycogen synthase kinase (GSK)-3beta is a constitutively active, proline-directed serine/threonine kinase that controls growth modulation and tumorigenesis through multiple intracellular signaling pathways. How GSK-3beta regulates signaling pathways induced by cytokines such as tumor necrosis factor (TNF) is poorly understood. In this study, we used fibroblasts derived from GSK-3beta gene-deleted mice to understand the role of this kinase in TNF signaling. TNF induced NF-kappaB activation as measured by DNA binding in wild-type mouse embryonic fibroblasts, but deletion of GSK-3beta abolished this activation. This inhibition was due to suppression of IkappaBalpha kinase activation and IkappaBalpha phosphorylation, ubiquitination, and degradation. TNF-induced NF-kappaB reporter gene transcription was also suppressed in GSK-3beta gene-deleted cells. NF-kappaB activation induced by lipopolysaccharide, interleukin-1beta, or cigarette smoke condensate was completely suppressed in GSK-3beta(-/-) cells. Deletion of GSK-3beta also abolished TNF-induced c-Jun N-terminal kinase and p44/p42 mitogen-activated kinase activation. Most surprisingly, TNF-induced Akt activation also required the presence of GSK-3beta. TNF induced expression of the NF-kappaB-regulated gene products cyclin D1, COX-2, MMP-9, survivin, IAP 1, IAP 2, Bcl-x(L), Bfl-1/A1, TRAF1, and FLIP in wild-type mouse embryonic fibroblasts but not in GSK-3beta(-/-) cells, and this correlated with potentiation of TNF-induced apoptosis as indicated by cell viability, annexin V staining, and caspase activation. Overall, our results indicate that GSK-3beta plays a critical role in TNF signaling and in the signaling of other inflammatory stimuli and that its suppression can be exploited as a potential target to inhibit angiogenesis, proliferation, and survival of tumor cells.


Structural foundation for the role of enterococcal PrgB in conjugation, biofilm formation, and virulence.
Type 4 Secretion Systems are a main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. In Gram-positives, these secretion systems often rely on surface adhesins to enhance cellular aggregation and mating-pair formation. One of the best studied adhesins is PrgB from the conjugative plasmid pCF10 of Enterococcus faecalis, which has been shown to play major roles in conjugation, biofilm formation, and importantly also in bacterial virulence. Since prgB orthologs exist on a large number of conjugative plasmids in various different species, this makes PrgB a model protein for this widespread virulence factor. After characterizing the polymer adhesin domain of PrgB previously, we here report the structure for almost the entire remainder of PrgB, which reveals that PrgB contains four immunoglobulin (Ig)-like domains. Based on this new insight, we re-evaluate previously studied variants and present new in vivo data where specific domains or conserved residues have been removed. For the first time, we can show a decoupling of cellular aggregation from biofilm formation and conjugation in prgB mutant phenotypes. Based on the presented data, we propose a new functional model to explain how PrgB mediates its different functions. We hypothesize that the Ig-like domains act as a rigid stalk that presents the polymer adhesin domain at the right distance from the cell wall.


Feasibility of Representing Data from Published Nursing Research Using the OMOP Common Data Model.
We explored the feasibility of representing nursing research data with the Observational Medical Outcomes Partners (OMOP) Common Data Model (CDM) to understand the challenges and opportunities in representing various types of health data not limited to diseases and drug treatments. We collected 1,431 unique data items from 256 nursing articles and mapped them to the OMOP CDM. A deeper level of mapping was explored by simulating 10 data search use cases. Although the majority of the data could be represented in the OMOP CDM, potential information loss was identified in contents related to patient reported outcomes, socio-economic information, and locally developed nursing intervention protocols. These areas will be further investigated in a follow up study. We will use lessons learned in this study to inform the metadata development efforts for data discovery.


MicroRNA MIR21 and T Cells in Colorectal Cancer.
The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell-mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided α level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3(+) and CD45RO(+) cells (Ptrend < 0.0005). The multivariate odds ratio of the highest versus lowest quartile of MIR21 for a unit increase in quartile categories of CD3(+) or CD45RO(+) cells was 0.44 [95% confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26-0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell-mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer.


One hundred consecutive cases of sentinel lymph node mapping in early colorectal carcinoma: detection of missed micrometastases.
Almost one third of patients with "node-negative" colorectal carcinoma (CRC) develop systemic disease. This implies that these patients have occult disease that is inadequately treated by surgery alone. We have coupled sentinel lymph node mapping and a focused pathologic examination to detect occult nodal micrometastases in CRC. Since 1996, sentinel lymph node mapping has been performed in 100 consecutive patients undergoing colectomy for CRC. Peritumoral injection of 0.5 to 1.0 ml of isosulfan blue dye was performed to demonstrate the sentinel node(s). All lymph nodes in the resection specimen were examined by routine hematoxylin and eosin staining. In addition, a focused examination of multiple sections of the sentinel nodes was performed using both hematoxylin and eosin and cytokeratin immunohistochemical analysis (CK-IHC). Overall, lymphatic mapping successfully demonstrated one to four sentinel lymph nodes in 97 (97%) of 100 patients. These sentinel nodes accurately reflected the status of the nodal basin in 92 (95%) of 97 patients. All five of the false negative cases occurred in T3/T4 tumors, and three of the five occurred during the first 30 cases in the experience. Unexpected lymphatic drainage was encountered in eight patients (8%) and altered the operative approach. Twenty-six patients were node positive by routine hematoxylin and eosin staining. Of the remaining 74 patients with hematoxylin and eosin-negative nodes, an additional 18 patients (24%) were upstaged by identification of occult nodal micrometastases that were missed on routine hematoxylin and eosin staining but detected on multiple sections (n = 5) or by CK-IHC (n = 13). The sentinel lymph nodes were the only positive nodes in 19 cases. Sentinel lymph node mapping may be performed in CRC with a high degree of success and accuracy. A focused pathologic examination of the sentinel node detects micrometastatic disease that is missed by conventional techniques in a significant proportion of patients with early CRC. Further studies are necessary to elucidate the clinical relevance of these micrometastases.


Cooperative N-Heterocyclic Carbene/Palladium-Catalyzed Enantioselective Umpolung Annulations.
A combination of NHC organocatalysis and transition-metal catalysis gives rise to fundamentally new cooperative reactivity and enables the regio- and enantioselective annulation reaction between enals and vinyl benzoxazinanones. The cooperative umpolung annulation eliminates mutual deactivation and leads to a diverse set of benzazepine derivatives in good yields with excellent enantioselectivities (up to 99% ee). The development of such a cooperative catalytic system dramatically expands the scope of NHC organocatalysis by opening up new metal-catalyzed reaction pathways for homoenolate intermediates.


The impact of onsite wastewater disposal systems on groundwater in areas inundated by Hurricane Sandy in New York and New Jersey.
Coastal onsite wastewater disposal systems (OWDS) were inundated by Hurricane Sandy's storm tide. This study compares the shallow groundwater quality (nutrients, pharmaceuticals, and hormones) downgradient of OWDS before and after Hurricane Sandy, where available, and establishes a baseline for wastewater influence on groundwater in coastal communities inundated by Hurricane Sandy. Nutrients and contaminants of emerging concern (CECs) were detected in shallow groundwater downgradient of OWDS in two settings along the New Jersey and New York coastlines: 1) a single, centralized OWDS in a park; and 2) multiple OWDS (cesspools) in low-density residential and mixed-use/medium density residential areas. The most frequently detected pharmaceuticals were lidocaine (40%), carbamazepine (36%), and fexofenadine, bupropion, desvenlafaxine, meprobamate, and tramadol (24-32%). Increases in the number and total concentration of pharmaceuticals after Hurricane Sandy may reflect other factors (seasonality, usage) besides inundation, and demonstrate the importance of analyzing for a wide variety of CECs in regional studies.


[Revascularization of the penis in vascular-induced erectile dysfunction: clinical results of the Hauri surgical method].
Hauri's modification of the procedure for operative penile revascularization has been known since 1983; it is characterized by an anastomosis between the inferior epigastric artery and the dorsal artery of the penis with an arteriovenous shunt with the deep dorsal vein of the penis. Since 1986 this surgical technique has been applied in 18 patients with vascular erectile dysfunction. Their average age was 47 years, and the mean observation period was 8 months. We did not consider the operation indicated unless the presence of pathologic vessels was demonstrated in the distal region of the internal pudendal artery by selective arteriography. After the operation, a 6-month therapy with platelet aggregation inhibitors is necessary. At postoperative follow-up 12 of the 18 patients reported that their sex life was unrestricted and they had spontaneous erections.


FlexTouch: An Insulin Pen-Injector with a Low Activation Force Across Different Insulin Formulations, Needle Technologies, and Temperature Conditions.
FlexTouch® (Novo Nordisk A/S, Bagsvaerd, Denmark) is a pen-injector with a torque spring mechanism requiring a low activation force. This laboratory-based study compared the activation force of FlexTouch during the injection of insulin with different needles and at temperature conditions within the range at which the device is recommended for use. Using a tensile tester, activation force was measured at maximum dose settings for insulin detemir (100 U/mL) and insulin degludec (100 and 200 U/mL) at standard (23°C ± 5°C), cool (5°C ± 3°C), and warm (30°C ± 2°C) conditions. Activation force was measured with two 32-gauge needles differing in internal diameter at standard conditions. At standard, cool, and warm conditions, estimated mean activation forces with 95% confidence interval were 5.71 newtons (N) (5.63-5.79), 5.94 N (5.83-6.06), and 5.69 N (5.58-5.80) with insulin detemir, 5.53 N (5.45-5.62), 5.56 N (5.44-5.67), and 5.33 N (5.22-5.44) with 100 U/mL insulin degludec, and 5.53 N (5.45-5.61), 5.83 N (5.71-5.94), and 5.56 N (5.45-5.68) with 200 U/mL insulin degludec, respectively. Mean activation forces were observed to be low with very small variability between measurements; however, the differences between insulins and temperature conditions were statistically significant. The activation force required by FlexTouch remained low across all situations tested. The differences between activation force needed with different insulins and temperature conditions were small and unlikely to be clinically meaningful.


Balkan endemic nephropathy is still present in the Kolubara region, Serbia.
Almost 50 years ago Balkan Endemic Nephropathy (BEN) was first described in Serbia in the village of Sopić where the first field examination was carried out in 1971. Our aim was to find out whether BEN is still present in this region. Prevalence data on BEN from a field examination run in 1971 were compared with the results of a cross-sectional study conducted in the same village in 1992. In addition, every new case of the disease diagnosed between 1971 and 1992 was recorded retrospectively. The prospective study included 50 members of five BEN families randomly selected from 28 BEN families registered in the village Sopić in 1992. The objective survey and examination of global and tubular kidney function was carried out in all examined persons once yearly in 1998, 1999, and 2000. The overall prevalence of BEN was 6.4% in 1971 and 8.9% in 1992. In the period of 21 years, 161 new BEN patients were detected in 28 families in which the disease had already been recorded. No new family affected by BEN and none of the new patients in 47 families registered previously as nonaffected were discovered. In the prospective study of five BEN families, three new BEN cases were discovered among 50 members, and two patients fulfilled criteria for BEN-suspected ones. Balkan Endemic Nephropathy (BEN) is still present in the village of Sopić, but the clinical course of the disease became more protracted over time. New cases of BEN appeared only in the affected families.


Clinicopathological and prognostic factors for long-term survival in Chinese patients with metastatic renal cell carcinoma treated with sorafenib: a single-center retrospective study.
Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1-27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7-16.4) months at a median follow-up time of 61.8 (95% CI: 16.2-97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.


No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50.
The 5' untranslated region of the fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats >or= 200, are associated with fragile X syndrome. Premutation alleles, repeats of approximately 55-199, are associated with a tremor-ataxia syndrome most commonly in older males and primary ovarian insufficiency in females. However, the neuropsychological impact of carrying a premutation allele is presently unclear in younger adults. In this study, we analyzed neuropsychological scores for 138 males and 506 females ascertained from the general population and from families with a history of fragile X syndrome. Subjects were age 18-50 years and had varying repeat lengths. Neuropsychological scores were obtained from measures of general intelligence, memory, and executive functioning, including attention. Principal component analysis followed by varimax rotation was used to create independent factors for analysis. These factors were modeled for males and females separately via a general linear model that accounted for correlation among related subjects. All models were adjusted for potential confounders, including age at testing, ethnicity, and household income. Among males, no repeat length associations were detected for any factor. Among females, only a significant association with repeat length and self-report attention (p < 0.01) was detected, with premutation carriers self-reporting significantly more attention-related problems compared to noncarriers. No significant interactions between repeat length and age were detected. Overall, these results indicate the lack of a global neuropsychological impact of carrying a premutation allele among adults under the age of 50.


Gender, employment, and retirement quality: a life course approach to the differential experiences of men and women.
Using a life course perspective in integrating 2 theories of retirement satisfaction--role theory and continuity theory--this study draws on a sample of retired men (n = 244) and women (n = 214), ages 50-72, to investigate factors contributing to the quality of their retirement experience. Overall, we find that men report greater retirement satisfaction than women, although the difference is small. For women, increased retirement quality is associated with good health, a continuous career (fewer years spent in part-time employment), an early retirement (though not earlier than anticipated), and a good postretirement income. For men, the key correlates with retirement quality are good health, an enjoyable preretirement job, low work-role salience, substantial preretirement planning, and retiring for internally motivated reasons (e.g., to do other things). These results underscore the importance of a life course focus on gendered pathways to and through life transitions such as retirement.


The British Journal of Anaesthesia. An informal history of the first 25 years.
In 1961, some 7 months after starting anaesthesia in the Leeds General Infirmary, I took out a subscription to the British Journal of Anaesthesia. It cost Pound Sterling3.15s.0d (Pound Sterling3.75) a year. The publishers John Sherratt and Son of Altringham) sent me the back numbers from the start of that year. I first had a paper published in the journal in 1965; first refereed a paper in 1969; joined the editorial board in 1975; and lasted there until 1998. The following account of the early years of the journal derives from the journal itself, and from records, letters and minutes of meetings kindly given to me by Dr Edmund Riding and Professor Andrew Hunter when they demitted offices with the journal. The history cannot be complete. Sadly, the earliest minutes books are lost. But there is much of interest covering the times when anaesthesia developed from the rag-and-bottle inhalation era to the use of intravenous anaesthetics, neuromuscular blocking agents, ventilators and monitoring. Thoracic and neurosurgical anaesthesia were revolutionized; cardiac surgery became possible; and resuscitation with intravenous fluids, blood and plasma all developed. Antibiotics improved care. Anaesthetists pioneered intensive care and latterly extended their roles in pain relief outside the operating theatre. All these developments have appeared in papers at some time in this journal. This is a personal view of the journal over its first 25 years: there will be errors and misinterpretations--these are mine.


Performance Invalidity Base Rates Among Healthy Undergraduate Research Participants.
Few studies have examined base rates of suboptimal effort among healthy, undergraduate students recruited for neuropsychological research. An and colleagues (2012, Conducting research with non-clinical healthy undergraduates: Does effort play a role in neuropsychological test performance? Archives of Clinical Neuropsychology, 27, 849-857) reported high rates of performance invalidity (30.8%-55.6%), calling into question the validity of findings generated from samples of college students. In contrast, subsequent studies have reported much lower base rates ranging from 2.6% to 12%. The present study replicated and extended previous work by examining the performance of 108 healthy undergraduates on the Dot Counting Test, Victoria Symptom Validity Test, Word Memory Test, and a brief battery of neuropsychological measures. During initial testing, 8.3% of the sample scored below cutoffs on at least one Performance Validity Test, while 3.7% were classified as invalid at Time 2 (M interval = 34.4 days). The present findings add to a growing number of studies that suggest performance invalidity base rates in samples of non-clinical, healthy college students are much lower than An and colleagues initial findings. Although suboptimal effort is much less problematic than suggested by An and colleagues, recent reports as high as 12% indicate including measures of effort may be of value when using college students as participants. Methodological issues and recommendations for future research are presented.


Laparoscopic excision of a large extra-adrenal perirenal myelolipoma.
Extra-adrenal myelolipoma is a very rare type of tumour. Laparoscopic removal of extra-adrenal myelolipoma has not been previously reported. We report the first case of laparoscopic excision of a large extra-adrenal perirenal myelolipoma.


The pollen- and embryo-specific Arabidopsis DLL promoter bears good potential for application in marker-free Cre/loxP self-excision strategy.
Marker-free transgenic plants can be generated with high efficiency by using the Cre/ lox P self-excision system controlled by the pollen- and embryo-specific Arabidopsis DLL promoter. In this work, we aimed to study the feasibility of using the pollen- and embryo-specific DLL promoter of the At4g16160 gene from Arabidopsis thaliana in a Cre/loxP self-excision strategy. A Cre/loxP self-excision cassette controlled by the DLL promoter was introduced into the tobacco genome via Agrobacterium-mediated transformation. No evidence for premature activation of the Cre/loxP system was observed in primary transformants. The efficiency of nptII removal during pollen and embryo development was investigated in transgenic T1 progenies derived from eight self- and four cross-pollinated T0 lines, respectively. Segregation and rooting assays were performed to select recombined T1 plants. Molecular analyses of these plants confirmed the excision event in all analysed T0 lines and marker-free transgenic T1 plants were obtained with efficiency of up to 96.2%. The Arabidopsis DLL promoter appears to be a strong candidate to drive Cre-mediated recombination not only in tobacco as a model plant, but also in other plant species.


A survival model for prognostic prediction based on ferroptosis-associated genes and the association with immune infiltration in lung squamous cell carcinoma.
Lung squamous cell carcinoma (LUSC) is the primary pathological type of lung cancer with a less favorable prognosis. This study attempts to construct a ferroptosis-associated signature associated with overall survival (OS) that can predict the prognosis of LUSC and explore its relationship with immune infiltration. A 5 ferroptosis-associated gene model was constructed by LASSO-penalized regression analysis to predict the prognosis of patients with LUSC in the TCGA database and validated in the GEO and TCGA databases. Patients were stratified into high-risk and low-risk groups by the median value of the risk scores, and the former prognosis was significantly worse (P<0.001). Additionally, we found a certain association between the two risk groups and immune infiltration through CIBERSORT. Meanwhile, the differentially expressed genes (DEGs) between normal and tumor tissue were used to perform functional analysis, which showed a significant association with leukocyte transendothelial migration pathways in the TCGA cohort. In addition, immune cell infiltration analysis confirmed that M2 macrophages were significantly highly expressed in the high-risk group. Overall, the model successfully established by ferroptosis-associated genes suggests that ferroptosis may be related to immune infiltration in LUSC.


Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults.
To investigate and describe the variability in cefepime exposures among 'real-world', critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations. A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2). Variability in the relationship between cefepime clearance and creatinine clearance (CrCL) was visualized, and a random, representative sample of 10 simulated patients was utilized to illustrate variability in cefepime exposures. A total of 75 adult medical ICU patients (52% female) and 98 serum cefepime samples were included in the study. Population parameter estimates for cefepime displayed a wide range of variation in Model 1 (CV: 45% to 95%), with low bias at the individual level at 0.226 mg/L but high bias in the population model 10.6 mg/L. Model 2 displayed similar fits, demonstrating that correcting for individual patient creatinine clearance slightly improves the bias of the population model (bias = 4.31 mg/L). Among 10 simulated patients that a clinician would deem similar from a dosing perspective (i.e. equivalent creatinine clearance), maximum concentrations after three simulated doses varied more than 8-fold from 41.2 to 339 mg/L at the 5th and 95th percentiles, and clearance profiles were highly different. Creatinine clearance estimates alone are inadequate for predicting cefepime exposures. Wide variations in cefepime exposure exist among ICU patients, even for those with similar kidney function estimates. Current population adjustment schemes based solely on creatinine clearance will result in unintended high and low exposures leading to safety and efficacy concerns, respectively.


Spatial targeted vector control is able to reduce malaria prevalence in the highlands of Burundi.
In a highland province of Burundi, indoor residual spraying and long-lasting insecticidal net distribution were targeted in the valley, aiming also to protect the population living on the hilltops. The impact on malaria indicators was assessed, and the potential additional effect of nets evaluated. After the intervention--and compared with the control valleys--children 1-9 years old in the treated valleys had lower risks of malaria infection (odds ratio, OR: 0.55), high parasite density (OR: 0.48), and clinical malaria (OR: 0.57). The impact on malaria prevalence was even higher in infants (OR: 0.14). Using nets did not confer an additional protective effect to spraying. Targeted vector control had a major impact on malaria in the high-risk valleys but not in the less-exposed hilltops. Investment in targeted and regular control measures associated with effective case management should be able to control malaria in the highlands.


Physicians Can Impact Patient Health.
Sugar-sweetened beverages account for nearly half the sugar Americans consume, at a time when over one-third of the population is obese and over two-thirds are considered overweight. To help reduce the health risks associated with obesity, physicians should consider targeting the one culprit most responsible for adding non-nutritional calories to the diet: sugar-sweetened soda. By helping patients to reduce or eliminate soda consumption, physicians can make a tremendous contribution to addressing the obesity crisis in the United States. The author offers suggestions for helping physicians to provide concrete steps their patients can use to decrease soda in their diets.


On the physical origin of the electro-mechano-acoustical analogy.
The electro-mechano-acoustical (EMA) analogy, introduced in the early 1900s, allows for the modeling of mechanical, acoustical, and EMA devices and systems using schematics of basic electrical elements, making possible the application of the well-established electrical network theory for studying, designing, and characterizing complex systems. By means of this elegant modeling, the behavior of intrinsically heterogeneous devices, such as microphones and loudspeaker drivers and systems, can be explained in each of the three domains and the mutual interactions between the electrical, mechanical, and acoustical parts can be precisely predicted. However, an open issue remains still unsolved: in all publications and textbooks, the EMA analogy has been always introduced only from the formal similarity of the equations describing the physical laws that regulate the basic EMA elements and a lack of insight into its physical fundamentals can be remarked. In this paper, an investigation on the existence of physical origins of the correspondences and similarities between the quantities and the laws describing the elements of electrical, mechanical, and acoustical domains is proposed and discussed. Historical research on the birth of EMA analogy theory with the fundamental contributions on its development given by the scientists and engineers is presented as well.


Recurrent NCOA2 gene rearrangements in congenital/infantile spindle cell rhabdomyosarcoma.
Spindle cell rhabdomyosarcoma (RMS) is a rare form of RMS with different clinical characteristics between children and adult patients. Its genetic hallmark remains unknown and it remains debatable if there is pathogenetic relationship between the spindle cell and the so-called sclerosing RMS. We studied two pediatric and one adult spindle cell RMS by next generation RNA sequencing and FusionSeq data analysis to detect novel fusions. An SRF-NCOA2 fusion was detected in a spindle cell RMS from the posterior neck in a 7-month-old child. The fusion matched the tumor karyotype and was confirmed by FISH and RT-PCR, which showed fusion of SRF exon 6 to NCOA2 exon 12. Additional 14 spindle cell (from 8 children and 6 adults) and 4 sclerosing (from 2 children and 2 adults) RMS were tested by FISH for the presence of abnormalities in NCOA2, SRF, as well as for PAX3 and NCOA1. NCOA2 rearrangements were found in two additional spindle cell RMS from a 3-month-old and a 4-week-old child. In the latter tumor, TEAD1 was identified by rapid amplification of cDNA ends (RACE) to be the NCOA2 gene fusion partner. None of the adult tumors were positive for NCOA2 rearrangement. Despite similar histomorphology in adults and young children, these results suggest that spindle cell RMS is a heterogeneous disease genetically as well as clinically. Our findings also support a relationship between NCOA2-rearranged spindle cell RMS occurring in young childhood and the so-called congenital RMS, which often displays rearrangements at 8q13 locus (NCOA2).


Interleukin-1β and interleukin-1receptor antagonist polymorphisms in Egyptian children with febrile seizures: A case-control study.
Febrile seizure is the most common seizure disorder of childhood. Of the pro-inflammatory cytokines, interleukin-1 is defined as the first endogenous pyrogen.We designed this study to investigate single-nucleotide polymorphisms (SNPs) situated at positions -31 (C/T), and -511 (C/T) of interleukin-1beta (IL-1β) gene promoter and interleukin-1receptor antagonist (IL-1RA) gene variable number of tandem repeats in intron 2 (VNTR); to determine whether these polymorphisms could be a marker of susceptibility to febrile seizures in Egyptian children and we also measured the serum level of IL-1β to assess its relation to such polymorphisms.This was a case-control study included 155 patients with febrile seizure, and matched with age, sex, ethnicity 155 healthy control subjects. IL-1β promoter at positions -31 (C/T), -511 (C/T), and IL-1RA gene VNTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) method.The frequency of the IL-1β-511 TT genotype and T allele at the same position were observed to be increased in patients with febrile seizures (FS) compared with the control group (odds ratio [OR]: 3.96; 95% confidence interval [CI]: 1.68-9.5; P = 0.001 for the TT genotype and OR: 1.65; 95% CI: 1.18-2.3; P = 0.003 for the T allele, respectively). The IL-1 RA II/II homozygous variant and IL-1 RA allele II were overrepresented in patients with FS than control group (OR: 4.02; 95% CI: 1.78-9.15; P = 0.001and OR: 1.73; 95% CI: 1.24-2.4; P = 0.001, respectively). We found a significant positive association between the IL-1 RA II/II genotype and susceptibility to FS in sporadic cases as did allele II at the same position (OR: 5.04; 95% CI: 2.1-12.5 for the IL-1 RA II/II genotype; P = 0.001) and (OR: 1.94; 95% CI: 1.3-2.8 for the allele II; P = 0.001, respectively). Carriers of the IL-1RA II/II homozygous variant and allele II had significantly higher serum levels of IL-1β compared with those with other genotypes and alleles.We demonstrate for the first time that the presence of a T allele or TT genotype at -511 of IL-1β promoter and IL-1RA II/II genotype constitute risk factors for developing FS in Egyptian children.


Biogenic amines in natural ciders.
Biogenic amines play an important physiological role in mammals, and high amounts of some exogenous amines in human diet may contribute to a wide variety of toxic effects. These amines are commonly found in many foodstuffs, particularly in fermented products such as cheese, meat products, beer, wine, and ciders. Here, the level of biogenic amines in some natural ciders was examined. Twenty-four samples of cider purchased from commercial sources were analyzed by reverse-phase high-performance liquid chromatography and fluorescence detection after precolumn derivatization with o-phthaldialdehyde. Amine levels were variable, ranging from not detected to 23 mg/liter. The average level of total biogenic amines in ciders was 5.94 +/- 8.42 mg/liter. Putrescine, histamine, and tyramine were the prevailing amines being present in 50.0, 37.5, and 33.3% of the ciders studied; very small amounts of ethylamine and phenylethylamine were observed in only one sample. Other cider parameters were analyzed to determine whether they affect the biogenic amine content in ciders, and the results were evaluated by applying cluster analysis and principal component analysis. Ciders that showed lower glycerol contents and higher amounts of 1,3-propanediol had much higher levels of histamine, tyramine, and putrescine, suggesting a high activity of lactic acid bacteria during cider making and thus the need for effective control of lactic acid bacteria.


Nitric Oxide Function and Nitric Oxide Synthase Evolution in Aquatic Chordates.
Nitric oxide (NO) is a key signaling molecule in almost all organisms and is active in a variety of physiological and pathological processes. Our understanding of the peculiarities and functions of this simple gas has increased considerably by extending studies to non-mammal vertebrates and invertebrates. In this review, we report the nitric oxide synthase (Nos) genes so far characterized in chordates and provide an extensive, detailed, and comparative analysis of the function of NO in the aquatic chordates tunicates, cephalochordates, teleost fishes, and amphibians. This comprehensive set of data adds new elements to our understanding of Nos evolution, from the single gene commonly found in invertebrates to the three genes present in vertebrates.


Relationships among victoria symptom validity test indices and personality assessment inventory validity scales in a large clinical sample.
The purpose of this study was twofold: (1) to examine the relationships among measures of cognitive symptom exaggeration (i.e., response accuracy and response latency) and (2) to examine the relationship between measures of cognitive and psychopathological symptom exaggeration. It was expected that Victoria Symptom Validity Test (VSVT) accuracy and latency measures would be significantly correlated, with invalid responders demonstrating longer response latencies. VSVT scores were also expected to correlate significantly with the Negative Impression Management (NIM) and Infrequency (INF) subscales of the Personality Assessment Inventory (PAI). VSVT and PAI data were collected from 300 patients during routine clinical neuropsychological evaluations. Results indicated that VSVT accuracy and latency measures were significantly and moderately correlated, and both types of VSVT scores were significantly, but modestly, related to NIM, but not INF. These findings suggest that VSVT response latencies may supplement accuracy scores in identifying patients who are exerting suboptimal effort on cognitive measures. These findings further suggest that measures of cognitive symptom validity only partially overlap with measures of psychopathological symptom exaggeration.


Cardiac tamponade: an initial presentation of SLE.
A 45-year-old woman presented with dyspnoea, chest pain, orthopnoea and bilateral leg oedema. On admission, she was found to have nephrotic syndrome and global pericardial effusion with impending tamponade for which pericardiocentesis was performed. The diagnosis of systemic lupus erythematosus was made based on the clinical and biochemical findings. She was also started on dialysis and immunosuppressants for lupus nephritis.


General AMBER Force Field Parameters for Diphenyl Diselenides and Diphenyl Ditellurides.
The General AMBER Force Field (GAFF) has been extended to describe a series of selenium and tellurium diphenyl dichalcogenides. These compounds, besides being eco-friendly catalysts for numerous oxidations in organic chemistry, display peroxidase activity, i.e., can reduce hydrogen peroxide and harmful organic hydroperoxides to water/alcohols and as such are very promising antioxidant drugs. The novel GAFF parameters are tested in MD simulations in different solvents and the (77)Se NMR chemical shift of diphenyl diselenide is computed using structures extracted from MD snapshots and found in nice agreement with the measured value in CDCl3. The whole computational protocol is described in detail and integrated with in-house code to allow easy derivation of the force field parameters for analogous compounds as well as for Se/Te organocompounds in general.


[The cardiac index dynamics of patients after the radical correction of tetralogy of Fallot depending on the level of the pressure-support ventilation (PSV) regimen].
Seventeen patients were examined, reoperated on for correction of Fallot's tetralogy on the open heart after a previous aortopulmonary anastomosis. Pressure support ventilation (PSV) was used in all patients during transfer to spontaneous pressure, making use of different levels of pressure support (20, 15, 13, 10, and 8 mm H2O). Decrease of pressure support from 20-15 mm H2O to 13 mm H2O resulted in a sharp increase of cardiac index. We explain this phenomenon by a drastic increase of the respiratory volume during the use of high PSV levels (20-15 mm H2O), surpassing 1.5-2 times the physiological and age-specific norm; this leads to a sharp increase of the mean intrathoracic pressure, disturbing the cardiovascular function.


Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival.
The transcription factor STAT5 has a critical role in B cell acute lymphoblastic leukemia (B-ALL). How STAT5 mediates this effect is unclear. Here we found that activation of STAT5 worked together with defects in signaling components of the precursor to the B cell antigen receptor (pre-BCR), including defects in BLNK, BTK, PKCβ, NF-κB1 and IKAROS, to initiate B-ALL. STAT5 antagonized the transcription factors NF-κB and IKAROS by opposing regulation of shared target genes. Super-enhancers showed enrichment for STAT5 binding and were associated with an opposing network of transcription factors, including PAX5, EBF1, PU.1, IRF4 and IKAROS. Patients with a high ratio of active STAT5 to NF-κB or IKAROS had more-aggressive disease. Our studies indicate that an imbalance of two opposing transcriptional programs drives B-ALL and suggest that restoring the balance of these pathways might inhibit B-ALL.


The Effect of Vibration Characteristics on the Atomization Rate in a Micro-Tapered Aperture Atomizer.
Because little is known about the atomization theory of a micro-tapered aperture atomizer, we investigated the vibration characteristics of this type of atomizer. The atomization mechanism of a micro-tapered aperture atomizer was described, and the atomization rate equation was deduced. As observed via microscopy, the angle of the micro-tapered aperture changes with the applied voltage, which proved the existence of a dynamic cone angle. The forward and reverse atomization rates were measured at various voltages, and the influence of the micro-tapered aperture and its variation on the atomization rate was characterized. The resonance frequency of the piezoelectric vibrator was obtained using a laser vibrometer, and the atomization rates were measured at each resonance frequency. From experiments, we found that the atomization rates at the first five resonance frequencies increased as the working frequency increased. At the fifth resonance frequency (121.1 kHz), the atomization rate was maximized (0.561 mL/min), and at the sixth resonance frequency (148.3 kHz), the atomization rate decreased significantly (0.198 mL/min). The experimental results show that the vibration characteristics of the piezoelectric vibrator have a relatively strong impact on the atomization rate. This research is expected to contribute to the manufacture of micro-tapered aperture atomizers.


Glycemic Control in Kenyan Children and Adolescents with Type 1 Diabetes Mellitus.
Background. Type 1 diabetes mellitus (T1DM) is the most common endocrine disorder in children and adolescents worldwide. While data about prevalence, treatment, and complications are recorded in many countries, few data exist for Sub-Saharan Africa. The aim of this study was to determine the degree of control in patients with T1DM aged 1-19 years over a 6-month period in 3 outpatient Kenyan clinics. It also sought to determine how control was influenced by parameters of patient and treatment. Methods. Eighty-two children and adolescents with T1DM were included in the study. Clinical history regarding duration of illness, type and dose of insulin, and recent symptoms of hypoglycemia/hyperglycemia were recorded. Glycaemia, HbA1c, and ketonuria were tested. HbA1c of 8.0% and below was defined as the cut-off for acceptable control. Results. The median HbA1c for the study population was 11.1% (range: 6.3-18.8). Overall, only 28% of patients had reasonable glycemic control as defined in this study. 72% therefore had poor control. It was also found that age above 12 years was significantly associated with poor control. Conclusions. African children and with T1DM are poorly controlled particularly in adolescents. Our data strongly support the necessity of Kenya children to receive more aggressive management and follow-up.


Is there a relationship between repopulation and hypoxia/reoxygenation? Results from human carcinoma of the cervix.
Long overall treatment times are detrimental for cure by radiotherapy and it has been argued that this may be due to repopulation occurring during the course of treatment. However, attempts to predict treatment outcome in relation to tumour proliferation, using pretreatment measurements of kinetic parameters such as Tpot or labelling index (LI) have not met with great success. One possible reason is that hypoxia/reoxygenation is linked to the growth of the tumour and its ability to repopulate. Data from studies in animal models have provided support for this possibility. We made measurement of tumour hypoxia, reoxygenation during treatment and pretreatment measurements of both Tpot and LI in groups of patients with cervix carcinoma undergoing radical radiation treatment. The data show a relationship between pretreatment pO2 measurements and treatment outcome, but reoxygenation did not show any association with treatment outcome. There was no significant association between pretreatment kinetic parameters and treatment outcome, nor was there any evidence of a relationship between pretreatment kinetic parameters and pO2. In the small group of 28 patients whose tumours underwent measurements of both pretreatment kinetic parameters (Tpot, LI) and reoxygenation, there was no relationship between these two sets of measurements. There was also no evidence that a combination of kinetic and reoxygenation measurements could be predictive of treatment outcome.


Effects of Six Commercial Saccharomyces cerevisiae Strains on Phenolic Attributes, Antioxidant Activity, and Aroma of Kiwifruit (Actinidia deliciosa cv.) Wine.
"Hayward" kiwifruit (Actinidia deliciosa cv.), widely planted all around the world, were fermented with six different commercial Saccharomyces cerevisiae strains (BM4×4, RA17, RC212, WLP77, JH-2, and CR476) to reveal their influence on the phenolic profiles, antioxidant activity, and aromatic components. Significant differences in the levels of caffeic acid, protocatechuate, and soluble solid content were found among wines with the six fermented strains. Wines fermented with RC212 strain exhibited the highest total phenolic acids as well as DPPH radical scavenging ability and also had the strongest ability to produce volatile esters. Wines made with S. cerevisiae BM 4×4 had the highest content of volatile acids, while the highest alcohol content was presented in CR476 wines. Scoring spots of wines with these strains were separated in different quadrants on the components of phenolics and aromas by principal component analyses. Kiwifruit wines made with S. cerevisiae RC212 were characterized by a rich fruity flavor, while CR476 strain and WLP77 strain produced floral flavors and green aromas, respectively. Altogether, the results indicated that the use of S. cerevisiae RC212 was the most suitable for the fermentation of kiwifruit wine with desirable characteristics.


Modified Genomic Sequencing PCR Using the MiSeq Platform to Identify Retroviral Integration Sites.
High-throughput mapping of retroviral vector integration sites (RIS) has become an invaluable tool to evaluate novel gene therapy vectors and to track clonal contribution in preclinical and clinical studies. Beard et al. (Methods Mol Biol 2014;1185:321-344) described an improved protocol developed for efficient capture, sequencing, and analysis of RIS that preserves gene-modified clonal contribution information. Here we describe adaptations to the previously published modified genomic sequencing PCR (MGS-PCR) protocol using the Illumina MiSeq paired-end sequencing platform. Lentiviral, gammaretroviral, and foamy virus vector integrations were analyzed. MGS-PCR using the MiSeq platform allows for the use of merged paired-end reads, which allows for efficient localization of RIS to published genomes.


Neoplastic and life-span effects of chronic exposure to tritium. I. Effects on adult rats exposed during pregnancy.
Female Sprague-Dawley rats were continuously exposed to equilibrium levels of tritiated water (HTO) during pregnancy. The tritium activities were 1, 10, 50, and 100 muCi HTO/ml body water which provided cumulative, whole-body radiation doses of approximately 6.6, 66, 330, and 660 rads. Administration of the radioisotope was terminated at parturition. Throughout their life-spans and at autopsy, the dams showed an increased incidence of mammary fibroadenomas at exposure to 330 and 660 rads. Although the data for the incidence of malignant mammary neoplasms were consistent with a linear dose response, the small numbers of tumors preclude specific definition of the dose-response curve. Postexposure life-spans for dams chronically exposed to 66, 330, and 660 rads during pregnancy were reduced by 14, 24, and 22%, respectively. Accelerated aging was also demonstrated in these rats: The mean age for mammary fibroadenoma onset decreased with an increasing dose of radiation.


Thermodynamic Insights into Variation in Thermomechanical and Physical Properties of Isotactic Polypropylene: Effect of Shear and Cooling Rates.
In order to elucidate the effect of shear and cooling process on structural, thermomechanical, and physical properties of polymer melt, excess entropy, a thermodynamic quantity is calculated from radial distribution function generated from equilibrated parts of the molecular simulation trajectories. The structural properties are calculated, which includes the density of polypropylene melt, end to end distance, radius of gyration of the polypropylene polymer chain, and monomer-monomer radial distribution function. Non-equilibrium molecular dynamics simulation was employed to investigate the role of the applied shear rate on the properties of polypropylene. Furthermore, a range of cooling rates were employed to cool the melt. Thermomechanical properties, such as Young's modulus, and physical properties, such as glass transition temperature, were determined for different cases. Results showed that slow cooling and high shear substantially improved the Young's modulus and glass transition temperature of the i-PP. Furthermore, a two-body contribution to the excess entropy was used to elucidate the structure-property relationships in the polymer melt as well as the glassy state and the dependence of shear and cooling rate on these properties. We have used the Rosenfeld excess entropy-viscosity relationship to calculate the viscous behavior of the polymer under a steady shear condition.


Famotidine in the short and long-term treatment of duodenal ulcer.
Famotidine was compared to ranitidine in a short-term study on the treatment of duodenal ulcer. Famotidine 20 mg. b.i.d., 40 mg. b.i.d. and 40 mg. nocte heal as many ulcer as ranitidine (90.9%, 91.7%, 83.3% and 100% respectively). A single 20 mg. bedtime dose shows to be effective on preventing ulcer recurrence for as long as 48 weeks; the 38% recurrence rate observed with famotidine was statistically different from the 78% observed with placebo. Diarrhoea was the most common complain observed during the short-term trial, followed by sleepiness and headache. The few and small biochemical alterations during the long-term treatment (increase in transaminases, alkaline phosphatase, glucose, BUN) could in no instance be directly related to the substances on use.


A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study.
The aim of this paper is to propose a pharmaceutical risk assessment strategy that goes beyond the usual characterisation of a clinical candidate molecule according to the biopharmaceutical classification system (BCS). This strategy was evaluated for a new CNS drug with poor solubility and good permeability. In a first step, GastroPlus was used to simulate the absorption process based on preformulation data. These input data involved a physicochemical drug characterisation including drug solubility measurements in simulated physiological media, as well as permeability determination. Further computer simulations were conducted to determine the sensitivity to changes of selected input values. Thus, oral bioavailability prediction was studied as a function of the particle size and drug solubility. The second part of the presented strategy for preclinical formulation development was to test specially designed formulations in a 2(3) screening factorial plan using the dog as the animal model. The factors were the dosage form, food effect and dose strength. One of the two experimental formulations was a capsule filled with the micronised drug, whereas the other formulation was a surfactant solution of the drug. Accordingly, a "worst case" formulation was compared with a "best case" drug solution over the clinically relevant dose range in fasted and fed dogs. The results of the computer simulation indicated that a fraction of the dose is dissolved in the stomach and precipitates partially in the small intestine. The simulation predicted almost full drug absorption during the GI transit time. Interestingly, the simulation implies that stomach drug solubility had little impact on overall fraction absorbed. The results also showed that changes of particle size and reference solubility within two orders of magnitude hardly affected the oral bioavailability. This in silico deduction was subsequently compared with the results of the dog studies. Indeed a surfactant drug solution showed no clear biopharmaceutical superiority over a solid capsule formulation on the average of both dose strengths in fasted and fed dogs. Despite the substantial variability of the in vivo data, the factorial screening design indicated marginal significant interaction between the dose level and feeding status. This can be viewed as a flag for the planning of further studies, since a potential effect of one factor may depend on the level of the other. In summary, the GastroPlus simulation together with the statistically designed dog study provided a thorough biopharmaceutical assessment of the new CNS drug. Based on these findings, it was decided to develop a standard granulate in capsules for phase I studies. More sophisticated formulation options were abandoned and so the clinical formulation development was conducted in a cost-efficient way.


Short communication: imputing genotypes using PedImpute fast algorithm combining pedigree and population information.
Routine genomic evaluations frequently include a preliminary imputation step, requiring high accuracy and reduced computing time. A new algorithm, PedImpute (http://dekoppel.eu/pedimpute/), was developed and compared with findhap (http://aipl.arsusda.gov/software/findhap/) and BEAGLE (http://faculty.washington.edu/browning/beagle/beagle.html), using 19,904 Holstein genotypes from a 4-country international collaboration (United States, Canada, UK, and Italy). Different scenarios were evaluated on a sample subset that included only single nucleotide polymorphism from the Bovine low-density (LD) Illumina BeadChip (Illumina Inc., San Diego, CA). Comparative criteria were computing time, percentage of missing alleles, percentage of wrongly imputed alleles, and the allelic squared correlation. Imputation accuracy on ungenotyped animals was also analyzed. The algorithm PedImpute was slightly more accurate and faster than findhap and BEAGLE when sire, dam, and maternal grandsire were genotyped at high density. On the other hand, BEAGLE performed better than both PedImpute and findhap for animals with at least one close relative not genotyped or genotyped at low density. However, computing time and resources using BEAGLE were incompatible with routine genomic evaluations in Italy. Error rate and allelic squared correlation attained by PedImpute ranged from 0.2 to 1.1% and from 96.6 to 99.3%, respectively. When complete genomic information on sire, dam, and maternal grandsire are available, as expected to be the case in the close future in (at least) dairy cattle, and considering accuracies obtained and computation time required, PedImpute represents a valuable choice in routine evaluations among the algorithms tested.


Enantioselective thiourea-catalyzed cationic polycyclizations.
A new thiourea catalyst is reported for the enantioselective cationic polycyclization of hydroxylactams. Both the yield and enantioselectivity of this transformation were found to vary strongly with the identity of a single aromatic residue on a common catalyst framework, with more expansive and polarizable arenes proving optimal. Evidence is presented for a mechanism in which stabilizing cation-pi interactions are a principal determinant of enantioselectivity.


Boundary conditions for stochastic solutions of the convection-diffusion equation.
Stochastic methods offer an attractively simple solution to complex transport-controlled problems, and have a wide range of physical, chemical, and biological applications. Stochastic methods do not suffer from the numerical diffusion that plagues grid-based methods, but they typically lose accuracy in the vicinity of interfacial boundaries. In this work we introduce some ideas and algorithms that can be used to implement boundary conditions in stochastic simulations of the convection-diffusion equation with accuracies comparable to the bulk phase. The algorithms have been tested in two-dimensional channel flows over a range of Peclet numbers, and compared with independent finite-difference calculations.


Home flow rates in evaluation of lower urinary tract symptoms in men.
We wanted to determine if 5-second home flow rates can be used in the evaluation in men with lower urinary tract symptoms (LUTS). Fifty previously untreated men with LUTS were evaluated by history and physical examination, international prostate symptom score (IPSS) questionnaire, and two methods of uroflowmetry. Each participant underwent three formal uroflow measurements using the Dantec UD5500 Mk2 machine and subjective 5-second home uroflow measurements twice daily for 7 days. The reliability of each test as well as correlation coefficients between the two methods of uroflowmetry were determined. The reliability for the average of the 14 home flow rates was 0.99 and the reliability for any single home flow was 0.82. Reliability for the average of three uroflows in measuring Qmax, Qave, flow times, and volume are 0.91, 0.91, 0.86, and 0.79, respectively. If single measurements are used, the values are 0.77, 0.78, 0.68, and 0.56. Home flow average is significantly different from Qmax and Qave (p < .001). No significant correlation was found between any of the uroflowmetry measurements or home flow average and IPSS or bother score. Home flows rates and uroflowmetry are reliable tests. There is a weak correlation between average home flows and Qmax and Qave. The greatest use of home flow rates probably lies in follow-up of patients who had either medical or surgical intervention for LUTS.


3D Foam-Like Composites of Mo2C Nanorods Coated by N-Doped Carbon: A Novel Self-Standing and Binder-Free O2 Electrode for Li-O2 Batteries.
The development of self-standing and binder-free O2 electrodes is significant for enhancing the total specific energy density and suppressing parasitic reactions for Li-O2 batteries, which is still a formidable challenge thus far. Here, a three-dimensional foam-like composite composed of Mo2C nanorods decorated by different amounts of N-doped carbon (Mo2C-NR@xNC (x = 5, 11, and 16 wt %)) was directly employed as the O2 electrode without applications of any binders and current collectors. Mo2C-NR@xNC presents a network microstructure with interconnected macropore and mesoporous channels, which is beneficial to achieving fast Li+ migration and O2 diffusion, facilitating the electrolyte impregnation, and providing enough space for Li2O2 storage. Additionally, the coated N-doped carbon layer can largely improve the electrochemical stability and conductivity of Mo2C. The cell with Mo2C-NR@11NC shows a considerable cyclability of 200 cycles with an overpotential of 0.28 V in the first cycle at a constant current density of 100 mA g-1, a superior reversibility associated with the formation and decomposition of Li2O2 as desired, and a high electrochemical stability. On the basis of the experimental results, the electrochemical mechanism for the cell using Mo2C-NR@11NC is proposed. These results represent a promising process in the development of a self-standing and binder-free foam-based electrode for Li-O2 batteries.


Nicotinamide protected first-phase insulin response (FPIR) and prevented clinical disease in first-degree relatives of type-1 diabetics.
After a study of ICA prevalence among relatives of Type-1 diabetics (DM1) in Santiago, Chile, parents of those who tested positive asked us to go on forward with an intervention study. We had screened 1021 relatives, of which 30 had shown ICA > or = 20 JDF units (2.9%). Among the 26/30 who participated in the intervention study, the baseline screening showed normal glucose tolerance in all, and the first-phase insulin response (FPIR) was normal in 24/26 individuals, which were randomized into Nicotinamide (n = 12; oral Nicotinamide, 1200 mg m(-2) day(-1)) and Placebo (n = 12) groups. The FPIRs and ICAs were monitored yearly. Compliance was monitored by urine Nicotinamide. The 1.5, 3.0 and 5-year life-table estimates of keeping the FPIR > or = 10th centile were, for Nicotinamide group 100% in all time points, and for Placebo these were 90.0% (c.i. = 100-71.4), 72.0% (c.i. = 100-37.1) and 0.0% (c.i. = 0.0-0.0) (p = 0.0091). The 5-year life-table estimates of remaining diabetes-free were 100% for Nicotinamide and 62.5% for Placebo (p = 0.0483). No adverse effects were observed. Oral Nicotinamide protected beta-cell function and prevented clinical disease in ICA-positive first-degree relatives of type-1 diabetes.


Endometriosis: etiology and pathophysiology of infertility.
The risk for developing endometriosis begins at puberty and extends to menopause in women of all races. The major pathway in the pathogenesis of this disease is the transplantation of endometrial cells to the pelvis and other abdominal organs via retrograde menstruation. Although retrograde menstruation appears to be a near universal occurrence, those women who are at particular risk for developing the disease have menstrual characteristics that increase the amount and duration of menstrual contamination of the pelvis. The ability of the body's immune system to remove this debris may play a significant independent role. In spite of the apparent association of infertility and endometriosis, there is a paucity of evidence to identify a clear cause-and-effect relationship or to clarify the specific mechanism(s) of infertility due to this enigmatic disease. Areas that warrant additional attention include the effect of endometriosis on ovulation, the impact of the immune system on the development of endometriosis, and the effect of peritoneal inflammation on reproduction. A better understanding of these areas will lead to more efficacious and specific therapies for endometriosis-associated infertility.


Albumin-constrained large-scale synthesis of renal clearable ferrous sulfide quantum dots for T1-Weighted MR imaging and phototheranostics of tumors.
Ultrasmall-sized iron-based nanoparticles are showing increasing potentials to be alternatives as T1-weighted magnetic resonance imaging (MRI) contrast agents to the currently-used gadolinium-based compounds. However, their synthesis particularly in a large-scale and green fashion is still a big challenge. Herein, we report an albumin-constrained strategy to synthesize tiny and highly dispersible ferrous sulfide (termed FeS@BSA) quantum dots (QDs) at ambient conditions. FeS@BSA QDs exhibit ultrasmall size of ca. 3.0 nm with an ultralow magnetization, affording them an appealing longitudinal relaxivity for T1-weighted MRI. The design principle leverages on albumin-mediated biomimetic synthesis and spatial isolation of the protein interface prevents bulk aggregation of the particles. Albumin was found to play crucial roles in the synthesis process: a constrained-microenvironment reactor for particle growth, a water-soluble layer for colloidal stability and a carrier for multi-functionality. This synthetic strategy was found facile, green and particularly large-scalable to 10 L. Mice experiments show good T1-weighted MRI capability of FeS@BSA QDs, significantly lighting the whole body organs, blood vessels and tumors. And interestingly, these QDs can be further used to conduct phototheranostic of tumor benefited from their intense absorption at near-infrared region. In particular, they can be cleared via glomerular filtration into bladder after treatment. Given this approach is biomimetic, scalable and does not require any complicated chemical synthesis or modifications, the method demonstrated here will find great potentials for clinical translation in T1-weighted MRI of diseases and inspire other functional tiny nanoprobes for biomedical applications.


Differential Associations of UPPS-P Impulsivity Traits With Alcohol Problems.
The UPPS-P model posits that impulsivity comprises five factors: positive urgency, negative urgency, lack of planning, lack of perseverance, and sensation seeking. Negative and positive urgency are the traits most consistently associated with alcohol problems. However, previous work has examined alcohol problems either individually or in the aggregate, rather than examining multiple problem domains simultaneously. Recent work has also questioned the utility of distinguishing between positive and negative urgency, as this distinction did not meaningfully differ in predicting domains of psychopathology. The aims of this study were to address these issues by (a) testing unique associations of UPPS-P with specific domains of alcohol problems and (b) determining the utility of distinguishing between positive and negative urgency as risk factors for specific alcohol problems. Associations between UPPS-P traits and alcohol problem domains were examined in two cross-sectional data sets using negative binomial regression models. In both samples, negative urgency was associated with social/interpersonal, self-perception, risky behaviors, and blackout drinking problems. Positive urgency was associated with academic/occupational and physiological dependence problems. Both urgency traits were associated with impaired control and self-care problems. Associations for other UPPS-P traits did not replicate across samples. Results indicate that negative and positive urgency have differential associations with alcohol problem domains. Results also suggest a distinction between the type of alcohol problems associated with these traits-negative urgency was associated with problems experienced during a drinking episode, whereas positive urgency was associated with alcohol problems that result from longer-term drinking trends.


Analysis of the AAAS gene in a Japanese patient with triple A syndrome.
Triple A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia and alacrima. It has recently been reported that this syndrome is caused by mutations in the AAAS gene. In the present study, we analyzed the AAAS gene in a Japanese patient with triple A syndrome. The patient was a Japanese girl previously reported by Hirose et al. (J Jpn Pediatr Soc 102: 912-915, 1998). The parents of the patient were first cousins. The patient was confirmed to have alacrima and isolated glucocorticoid deficiency at the age of 2 years. She later developed achalasia of the cardia, and was diagnosed as having triple A syndrome. The AAAS gene was amplified by the PCR method, and the PCR products were directly sequenced. The patient was homozygous for a novel nonsense mutation Q237X, changing codon 237 encoding Gln (CAA) to a stop codon (TAA). The parents were heterozygous for the Q237X mutation. The AAAS gene encodes a protein of 546 amino acids, ALADIN. The Q237X mutation is predicted to result in a truncated and presumably non-functioning ALADIN protein, thus causing the clinically manifest syndrome in the patient. To our knowledge, this is the first report on AAAS gene mutations in Japan.


Respiratory Muscle Weakness in Thyrotoxic Periodic Palsy: A Lesson to Remember.
Thyrotoxic periodic palsy (TPP) is a sporadic form of hypokalemic periodic palsy that may occur in association with hyperthyroidism mostly with Graves' disease. Acute thyrotoxic periodic palsy is a disorder most commonly seen in Asian men and characterized by abrupt onset of hypokalemia and paralysis. The disorder primarily affects the lower extremities and can involve all four limbs and presents as acute flaccid paralysis. The diagnosis of thyrotoxic periodic palsy is not difficult, but the disease's low incidence and many differentials for acute flaccid paralysis delay and complicate the diagnosis. TPP is not related to the etiology, severity, and duration of thyrotoxicosis. The treatment is similar to hypokalemic periodic palsy with potassium supplementation and initiation of antithyroid drugs and beta-blocker therapy. Here a similar case of quadriparesis is reported, which got precipitated after abrupt cessation of carbimazole in a young male. This initially was thought to be a case of hypokalemic periodic palsy and was later diagnosed to be TPP and recovered after initiating antithyroid drugs and potassium supplementation.


Validation of a Photonumeric Assessment Scale for Grading the Slope of the Asian Forehead.
As the number of aesthetic treatments has grown, so have the number of photonumeric assessment scales used to compare the effectiveness of these aesthetic treatments in specific anatomical areas; however, these are primarily based on Caucasian features. To assess the validity of the first aesthetic scale for assessing the slope of the Asian forehead. A secondary objective was to correlate this scale with subject demographics and baseline characteristics. During 2 validation sessions, 13 raters assessed full frontal and lateral facial images of female (n = 28; 56.0%) and male (n = 22; 44%) subjects. For each subject, the severity of forehead sloping was graded from 0 (convex forehead, optimal forehead volume) to 4 (concave forehead, very severe sloping). Raters also assessed the age of each subject and the estimated aesthetic treatment effort required to treat each subject. Inter-rater reliability was "substantial" with scores of 0.67 and 0.68 for the first and second validation sessions, indicating high reliability. BMI showed the highest correlation with the scale and was a significant predictor in the final regression model. This photonumeric assessment scale will be useful for assessing the slope of the Asian forehead in both clinical and research settings.


Ultrasonography for Dorsal-Sided Wrist Pain in a Combat Environment: Technique, Pearls, and a Case Report of Dynamic Evaluation of the Scapholunate Ligament.
Ultrasonography is a commonly utilized tool in orthopedic surgery for the diagnosis and treatment of a variety of musculoskeletal conditions, including pathology about the wrist. Its value should not be underestimated when other diagnostic resources are unavailable - such as in a combat setting where ultrasounds, but not X-ray, are a standard equipment item. An active duty soldier presented to an orthopedic provider in an austere environment with chronic dorsal wrist pain due to a previous fall. Physical examination and dynamic ultrasound examination allowed the deployed provider to diagnose a scapholunate ligament injury. The patient was appropriately evacuated to a higher level of care without the need for X-ray or other advanced imaging modalities. Making this readily available resource a standard tool for providers deployed to a forward location could be beneficial for efficient and appropriate patient evacuation for musculoskeletal injuries. It can also rule out injuries that would otherwise have required unnecessary soldier movement through hostile territory for diagnostic tests such as X-rays. In addition, a simple technique and pearls for ultrasonography of the wrist are provided.


Biomarkers for exposure to sand flies bites as tools to aid control of leishmaniasis.
Intense research efforts so far have not been sufficient to reduce leishmaniasis burden worldwide. This disease is transmitted by bites of infected sand flies, which inject saliva in the host skin in an attempt to obtain a blood meal. Sand fly saliva has an array of proteins with diverse pharmacological properties that modulates the host homeostatic and immune responses. Some of these proteins are also immunogenic and can induce both cellular and humoral immune responses. Recently, the use of sand fly salivary proteins to estimate exposure to sand fly bites and consequently the risk of infection has emerged. Here, we review evidence that supports the use of the host immune responses against sand fly salivary proteins to estimate risk of infection. We also discuss how the use of recombinant salivary proteins can optimize serological surveys and provide guidance for the implementation of specific measures for disease control in endemic areas.


Patient knowledge about human papillomavirus and relationship to history of abnormal Papanicolaou test results.
To assess patient knowledge about human papillomavirus (HPV) and determine if self-report of a previous abnormal Papanicolaou test result improves knowledge. A survey was designed and administered to patients at three obstetrics and gynecology clinics in Milwaukee, WI. The anonymous surveys assessed demographics, history of sexually transmitted infections or abnormal Papanicolaou test results, and knowledge about HPV and cervical cancer. The chi and Wilcoxon tests were used for statistical comparisons. Three hundred sixty-three surveys were collected, representing a diverse patient population. Forty-two percent of patients had heard of HPV. Women who reported a history of abnormal Papanicolaou test results were not more likely to have heard of HPV or to know that it causes cervical cancer than those who did not report abnormal Papanicolaou test results. There is no significant difference in knowledge about HPV between patients who reported a history of abnormal Papanicolaou tests and those who did not.


Follicular Thyroid Carcinoma: How Have Histologic Diagnoses Changed in the Last Half-Century and What Are the Prognostic Implications?
Follicular thyroid carcinoma (FTC) comprises 10% of differentiated thyroid cancers. Diagnostic controversy and interobserver variability render the practical diagnosis of FTC difficult. Overall survival rates vary (46-97%). The aims of this study were to review FTC histologically at the authors' tertiary care institution and to evaluate long-term survival and recurrence. Diagnostic slides from 66 FTC cases (1965-2007) were reviewed by three pathologists from two institutions (blinded to clinical outcomes), and consensus was obtained. Patient demographics, tumor characteristics, and treatment, survival, and recurrence data were collected. Thyroid cancer-specific and recurrence-free survival were calculated by original and reclassified diagnoses. Forty-seven cases (71%) were reclassified: 24 (36%) to papillary thyroid carcinoma (PTC), 18 (27%) to follicular adenoma (FA), and five (8%) to poorly differentiated carcinoma (PDC). Nineteen (29%) maintained a diagnosis of FTC. The extent of surgical resection and rates of radioiodine treatment did not differ by reclassification diagnosis. Pre-review FTC-specific survival was 83.5% and 75.1% at 10 and 20 years, respectively. Following contemporary reclassification, FTC-specific survival was 77% and 33.7% at 10 and 20 years, respectively. There were no cancer-specific deaths in the FA or PTC groups. Over the past 50 years, changes in our understanding of the pathogenesis, histology, and behavior of thyroid carcinoma may partially account for the changes in histologic diagnosis. Elimination of PTC and FA "contaminants" led to decrease in survival following reclassification. Variability in histologic interpretation contributes to diagnostic challenges in follicular lesions. Histologic review of thyroid tumors for research studies is crucial, especially given the ever-changing diagnostic criteria.


Between empowerment and powerlessness: separated minors in Sweden.
This article analyzes the migration experiences of thirteen separated minors who arrived in Sweden between 1943 and 2008. Using the framework of "dislocation" and the "liberated self," this chapter shows that the experiences of separated minors are shaped in the intersection between contexts and conditions of transnational migration and the Swedish reception system. Their efforts to continue living based on the past and building a new life during a period of transition between different countries and between childhood and adulthood can be described as "a life on hold." The paradox that migration serves simultaneously to empower and render children powerless is discussed.


Attention-deficit hyperactivity symptoms and disorder in eating disorder inpatients.
The objective of this study was to determine the prevalence of attention-deficit hyperactivity disorder (ADHD) symptoms and a DSM-IV ADHD diagnosis in women admitted for treatment of an eating disorder. One hundred eighty-nine inpatient women with an eating disorder were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and ADHD interview from the Multi-international Psychiatric Interview (MINI). Twenty-one percent of the sample reported at least six current ADHD symptoms, but the estimated prevalence rate for a diagnosis of ADHD in this population was only 5.8% (95% CI: 2.6%-9.5%). Most current ADHD inattentive symptoms appeared after childhood suggesting late-onset non-ADHD origins. Current inattention symptoms in those without a diagnosis of ADHD correlated with higher BMI (p < .0001), symptoms of bulimia nervosa and current level of depression symptoms (p = .025). Although current ADHD symptoms were commonly endorsed in this population, clinicians should carefully examine for childhood symptom-onset of ADHD.


Comprehensive species set revealing the phylogeny and biogeography of Feliformia (Mammalia, Carnivora) based on mitochondrial DNA.
Extant Feliformia species are one of the most diverse radiations of Carnivora (~123 species). Despite substantial recent interest in their conservation, diversification, and systematic study, no previous phylogeny contains a comprehensive species set, and no biogeography of this group is available. Here, we present a phylogenetic estimate for Feliformia with a comprehensive species set and establish a historical biogeography based on mitochondrial DNA. Both the Bayesian and maximum likelihood phylogeny for Feliformia are elucidated in our analyses and are strongly consistent with many groups recognized in previous studies. The mitochondrial phylogenetic relationships of Felidae were for the first time successfully reconstructed in our analyses with strong supported. When divergence times and dispersal/vicariance histories were compared with historical sea level changes, four dispersal and six vicariance events were identified. These vicariance events were closely related with global sea level changes. The transgression of sea into the lowland plains between Eurasia and Africa may have caused the vicariance in these regions. A fall in the sea level during late Miocene to Pliocene produced the Bering strait land bridge, which assisted the migration of American Feliformia ancestors from Asia to North America. In contrast with the 'sweepstakes hypothesis', our results suggest that the climate cooling during 30-27 Ma assisted Feliformia migration from the African mainland to Madagascar by creating a short-lived ice bridge across the Mozambique Channel. Lineages-through-time plots revealed a large increase in lineages since the Mid-Miocene. During the Mid-Miocene Climatic Optimum, the ecosystems and population of Feliformia rapidly expanded. Subsequent climate cooling catalyzed immigration, speciation, and the extinction of Feliformia.


Prevention, early intervention, and harm reduction of substance use in adolescents.
This paper presents a systematic review on the effectiveness of prevention, early intervention, and harm reduction including treatment of substance abuse among adolescents for tobacco, alcohol and illicit drugs. Taxation, public consumption bans, restriction on advertisements, and minimum legal age for consumption, are effective measures to reduce the use of tobacco and alcohol. School-based prevention and skill-training interventions are effective tools to reduce substance use among adolescents. Social norms and intervention to reduce substance use in adolescents do not have strong evidence of effectiveness. Road-side testing and reduction of injection related harm are effective. However, further research is needed to support it. Moreover, the available research evidence comes from the Western countries with questionable applicability in Indian setting. Research is needed to increase the evidence base on interventions that aim to reduce the high burden of substance use in adolescents in India.


ER-851, a Novel Selective Inhibitor of AXL, Overcomes Resistance to Antimitotic Drugs.
Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-851, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemoresistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, cotreatment of ER-851 and antimitotic drugs produced an antitumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-851 is a promising candidate therapeutic agent for use against AXL-expressing antimitotic-resistant tumors.


Characterization of a novel thogotovirus isolated from Amblyomma testudinarium ticks in Ehime, Japan: A significant phylogenetic relationship to Bourbon virus.
The genus Thogotovirus, as represented by Thogoto virus and Dhori virus, comprises a group of arthropod-borne viruses, most members of which are transmitted by ticks. Here we report the genetic and biological characterization of a new thogotovirus, designated Oz virus (OZV), isolated from the hard tick Amblyomma testudinarium in Ehime, Japan. OZV efficiently replicated and induced a cytopathic effect in Vero cells, from which enveloped pleomorphic virus particles were formed by budding. OZV could also replicate in BHK-21 and DH82 cells and caused high mortality in suckling mice after intracerebral inoculation. Phylogenetic analyses of six viral proteins indicated that OZV is clustered with Dhori and related viruses, and is most closely related in glycoprotein (GP) and matrix protein (M) sequences to Bourbon virus, a human-pathogenic thogotovirus discovered recently in the United States. Our findings emphasize the need for understanding the geographic distribution and ecology of OZV and related viruses and for reevaluation of the medical and public health importance of thogotoviruses.


Goals of hospice care.
Hospice is a service and philosophy of care for terminally ill patients. Its roots extend back to the Middle Ages, but it was developed into its present form by Dr Cicely Saunders at St Christopher's Hospice in London. Hospices use teamwork and careful listening to the patient to achieve the following goals (whether the patient is at home or in an inpatient unit): (a) to relieve the pain and suffering of the terminally ill; (b) to make possible a "good" death; (c) to help the family; (d) to assist in the search for meaning.


Elevational size variation and two new species of torrent frogs from Peninsular Malaysia (Anura: Ranidae: Amolops Cope).
Previously, only one species of torrent frog (Amolops larutensis) was thought to occur throughout Peninsular Malaysia. However, genomic work has demonstrated that populations from eastern Peninsular Malaysia form two separate lineages that are genetically distinct from A. larutensis that is now restricted to the western half of Peninsular Malaysia. This study demonstrates that all three lineages can be morphologically distinguished from each other, thereby providing additional support for the recognition of the eastern lineages as two distinct species. These lineages are described herein as Amolops gerutu sp. nov. from the eastern states of Kelantan, Terengganu, and Pahang, and A. australis sp. nov. from the southern-most state of Johor. In general, these two new species form a clade that is sister to A. larutensis and can be readily distinguished from it by having: (1) considerably denser and more pronounced dorsal tubercles, and (2) the posterodorsal surface of thighs having dense, dark stippling as opposed to broad vermiculations. Although differences in other morphometric characters were detected, their utility as diagnostic characters should be applied with caution due to the large intraspecific variation that overlaps among different species in many of the characters we measured. As such, we advocate for the use of tuberculation and pattern of the posterodorsal portion of the thighs as primary diagnostic characters. These characters can readily distinguish A. larutensis from the two new species. To differentiate A. australis sp. nov. from A. gerutu sp. nov. and A. larutensis, body size can be a good diagnostic character as A. australis sp. nov. is significantly smaller in both males (mean = 31.04 ± 1.59 mm) and females (mean = 46.48 ± 3.2 mm). Additionally, we show a strong positive correlation between body size and elevation, with populations from montane forests (>900 m asl) being considerably larger than populations at lower elevations.


Universality of local dissipation scales in buoyancy-driven turbulence.
We report an experimental investigation of the local dissipation scale field eta in turbulent thermal convection. Our results reveal two types of universality of eta. The first one is that, for the same flow, the probability density functions (PDFs) of eta are insensitive to turbulent intensity and large-scale inhomogeneity and anisotropy of the system. The second is that the small-scale dissipation dynamics in buoyancy-driven turbulence can be described by the same models developed for homogeneous and isotropic turbulence. However, the exact functional form of the PDF of the local dissipation scale is not universal with respect to different types of flows, but depends on the integral-scale velocity boundary condition, which is found to have an exponential, rather than Gaussian, distribution in turbulent Rayleigh-Bénard convection.


Shock avoidance by discrimination learning in the shore crab (Carcinus maenas) is consistent with a key criterion for pain.
Nociception allows for immediate reflex withdrawal whereas pain allows for longer-term protection via rapid learning. We examine here whether shore crabs placed within a brightly lit chamber learn to avoid one of two dark shelters when that shelter consistently results in shock. Crabs were randomly selected to receive shock or not prior to making their first choice and were tested again over 10 trials. Those that received shock in trial 2, irrespective of shock in trial 1, were more likely to switch shelter choice in the next trial and thus showed rapid discrimination. During trial 1, many crabs emerged from the shock shelter and an increasing proportion emerged in later trials, thus avoiding shock by entering a normally avoided light area. In a final test we switched distinctive visual stimuli positioned above each shelter and/or changed the orientation of the crab when placed in the chamber for the test. The visual stimuli had no effect on choice, but crabs with altered orientation now selected the shock shelter, indicating that they had discriminated between the two shelters on the basis of movement direction. These data, and those of other recent experiments, are consistent with key criteria for pain experience and are broadly similar to those from vertebrate studies.


Catheter probe endoscopic ultrasonography by using cold lubricating jelly-filled method for esophageal subepithelial tumors.
Catheter probe endoscopic ultrasonography (C-EUS) by ultrasonographic jelly-filled method has been used to evaluate esophageal subepithelial tumors (SETs). Ultrasonographic jelly is safe on the skin, but its internal safety has not been demonstrated. The jelly stored at room temperature is easily injected into the esophagus through the instrument channel of the endoscope. However, using jelly stored at room temperature remains problematic because the jelly is drained rapidly. We used cold lubricating jelly and an intravenous extension tube to resolve these problems. In this study, we evaluated the safety and efficacy of cold lubricating jelly-filled method. The medical records of patients who underwent C-EUS by using water or cold lubricating jelly-filled method for esophageal SETs from March 2013 to September 2016 in Gangneung Asan hospital were reviewed. Clinical characteristics and EUS findings were evaluated retrospectively. Image quality and procedure time between water and cold lubricating jelly-filled method were compared retrospectively. This study included 138 patients (74 males, 64 females) with esophageal SET with a mean age of 57.1 ± 11.1 years. Thirty-four patients had lesions in the upper esophagus, 58 patients had lesions in the middle esophagus, and 46 patients had lesions in the lower esophagus. The EUS diagnoses were leiomyoma (82.6%), hemangioma (4.3%), extrinsic compressive lesion (3.6%), granulosa cell tumor (2.9%), ectopic calcification (1.4%), cyst (1.4%), lipoma (0.7%), varix (0.7%), and inconclusive lesion (2.2%). The mean image score in the cold lubricating jelly filled-method group was higher than that in the water-filled method group (3.2 ± 0.7 vs. 2.8 ± 0.7, P = 0.002). The procedure time in the cold lubricating jelly filled-method group was shorter than that in the water-filled method group (10 minutes 27 seconds ± 4 minutes 22 seconds versus 13 minutes 20 seconds ± 6 minutes 20 seconds, P = 0.045). No procedure-related complication was observed. C-EUS using the cold lubricating jelly-filled method seems to provide better image quality and shorter procedure time compared with C-EUS using the water-filled method.


Using Distributed Data over HBase in Big Data Analytics Platform for Clinical Services.
Big data analytics (BDA) is important to reduce healthcare costs. However, there are many challenges of data aggregation, maintenance, integration, translation, analysis, and security/privacy. The study objective to establish an interactive BDA platform with simulated patient data using open-source software technologies was achieved by construction of a platform framework with Hadoop Distributed File System (HDFS) using HBase (key-value NoSQL database). Distributed data structures were generated from benchmarked hospital-specific metadata of nine billion patient records. At optimized iteration, HDFS ingestion of HFiles to HBase store files revealed sustained availability over hundreds of iterations; however, to complete MapReduce to HBase required a week (for 10 TB) and a month for three billion (30 TB) indexed patient records, respectively. Found inconsistencies of MapReduce limited the capacity to generate and replicate data efficiently. Apache Spark and Drill showed high performance with high usability for technical support but poor usability for clinical services. Hospital system based on patient-centric data was challenging in using HBase, whereby not all data profiles were fully integrated with the complex patient-to-hospital relationships. However, we recommend using HBase to achieve secured patient data while querying entire hospital volumes in a simplified clinical event model across clinical services.


[Comparing high- and low-lethality factors regarding attempted suicide-associated risk factors].
This study was aimed at identifying the most common risk factors associated with suicide attempts to determine differences between risk factors present in patients regarding their low-lethality and high-fatality suicide attempts. 106 patients from both sexes who had been hospitalised in a psychiatric unit following their attempts at suicide were interviewed; they were divided into two groups: low-lethality and high-lethality suicide attempt patients. 58.5 % of the 106 patients were placed in the low-lethality group and 41.5 % in the high-lethality group. The highest rates occurred in the high-lethality group but only two factors had significant statistical difference: "living alone" and "prior alcohol poisoning". 77.4 % of the sample were aged under 39, 7 % were female and 31 % male. Having a family background of alcoholism, previously attempted suicide, generalised anxiety and dysthymia had the highest percentages as risk factors associated with attempted suicide in both groups. The risk factors having the highest percentages were consistent with those reported in the literature. The fact of living alone and having previously suffered alcohol poisoning had statistically significant differences in this study. No significant differences were found in the rest of the factors studied here.