Biophysical and economic water productivity of dual-purpose cattle farming.
This study analyzes key factors influencing water productivity in cattle rearing, particularly in contexts characterized by water scarcity. This was done through year-round monitoring of on-farm practices within five smallholder farms located in the Saïss area (northern Morocco). The on-farm monitoring protocol consisted of characterizing: (i) volumes of water used for fodder production and distinguished by source (rainfall, surface irrigation and groundwater), (ii) virtual water contained in off-farm feed resources, (iii) total forage biomass production, (iv) dietary rations fed to lactating cows and their calves and (v) milk output and live weight gain. Findings reveal a mean water footprint of 1.62±0.81 and 8.44±1.09 m3/kg of milk and of live weight gain, respectively. Groundwater represented only 13.1% and 2.2% of the total water used to get milk and live weight gain, respectively, while rainfall represented 53.0% and 48.1% of the total water for milk and live weight gain, respectively. The remaining water volumes used came from surface irrigation water (7.4% for milk and 4.0% for live weight gain) and from virtual water (26.5% for milk and 44.7% for live weight gain). The results also revealed a relatively small gross margin per m3 of water used by the herd, not exceeding an average value of US $ 0.05, when considering both milk and live weight. Given the large variability in farm performances, which affect water productivity in cattle rearing throughout the production process, we highlight the potential for introducing a series of interventions that are aimed at saving water, while concurrently improving efficiency in milk production and live weight gain. These interventions should target the chain of production functions that are implemented throughout the process of water productivity in cattle rearing. Moreover, these interventions are of particular importance given our findings that livestock production depends largely upon rainfall, rather than groundwater, in an area afflicted with sustained droughts, overexploitation of groundwater resources and growing water scarcity.


Relationship between transmission of Porphyromonas gingivalis and fimA type in spouses.
Porphyromonas gingivalis is one of the major microbial pathogens associated with chronic periodontitis. To eradicate such pathogens by periodontal therapy, it is essential to clarify the source of infection. Recent findings suggest that the genotype of the fimbriae is one of the important factors in infection by P. gingivalis. The objectives of the present study were to investigate the transmission of P. gingivalis between spouses and to determine the relationship between P. gingivalis fimA type and colonization. A total of 14 couples were selected to investigate the transmission of P. gingivalis and its association with the fimA types. To examine the distribution of fimA type in the general population, 32 subgingival plaque samples from 47 patients with periodontitis were also tested. The transmission of P. gingivalis strains was determined by using pulsed field gel electrophoresis (PFGE). P. gingivalis strains isolated from the couples and subgingival dental plaque samples were studied for fimA classification. The PFGE patterns of P. gingivalis strains from matched husbands and wives were identical for six of the 14 couples. In five of these six couples (83.3%), P. gingivalis strains harboring the type II fimA gene were present. The proportion of type II fimA in the strains isolated from couples with probable intrafamilial transmission was significantly higher than that in patients with periodontitis or in the group of samples isolated from one member of a couple. This study suggests that fimA type II, even though widely distributed in patients with periodontitis, may be an important factor in the transmission of P. gingivalis between spouses.


Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ.
Cystic kidney diseases (CKDs) affect millions of people worldwide. The defining pathological features are fluid-filled cysts developing from nephric tubules due to defective flow sensing, cell proliferation and differentiation. The underlying molecular mechanisms, however, remain poorly understood, and the derived excretory systems of established invertebrate models (Caenorhabditis elegans and Drosophila melanogaster) are unsuitable to model CKDs. Systematic structure/function comparisons revealed that the combination of ultrafiltration and flow-associated filtrate modification that is central to CKD etiology is remarkably conserved between the planarian excretory system and the vertebrate nephron. Consistently, both RNA-mediated genetic interference (RNAi) of planarian orthologues of human CKD genes and inhibition of tubule flow led to tubular cystogenesis that share many features with vertebrate CKDs, suggesting deep mechanistic conservation. Our results demonstrate a common evolutionary origin of animal excretory systems and establish planarians as a novel and experimentally accessible invertebrate model for the study of human kidney pathologies.


Search for High-Mass Resonances Decaying to τν in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.
A search for high-mass resonances decaying to τν using proton-proton collisions at sqrt[s]=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb^{-1}. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W^{'} bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2-3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level.


Perspective of Turkish Medicine Students on Cancer, Cancer Treatments, Palliative Care, and Oncologists (ARES Study): a Study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).
Cancer is one of the most common causes of death all over the World (Rahib et al. in Cancer Res 74(11):2913-2921, 2014; Silbermann et al. in Ann Oncol 23(Suppl 3):iii15-iii28, 2012). It is crucial to diagnose this disease early by effective screening methods and also it is very important to acknowledge the community on various aspects of this disease such as the treatment methods and palliative care. Not only the oncologists but every medical doctor should be educated well in dealing with cancer patients. Previous studies suggested various opinions on the level of oncology education in medical schools (Pavlidis et al. in Ann Oncol 16(5):840-841, 2005). In this study, the perspectives of medical students on cancer, its treatment, palliative care, and the oncologists were analyzed in relation to their educational status. A multicenter survey analysis was performed on a total of 4224 medical school students that accepted to enter this study in Turkey. After the questions about the demographical characteristics of the students, their perspectives on the definition, diagnosis, screening, and treatment methods of cancer and their way of understanding metastatic disease as well as palliative care were analyzed. The questionnaire includes questions with answers and a scoring system of Likert type 5 (absolutely disagree = 1, completely agree = 5). In the last part of the questionnaire, there were some words to detect what the words "cancer" and "oncologist" meant for the students. The participant students were analyzed in two study groups; "group 1" (n = 1.255) were phases I and II students that had never attended an oncology lesson, and "group 2" (n = 2.969) were phases III to VI students that had attended oncology lessons in the medical school. SPSS v17 was used for the database and statistical analyses. A value of p < 0.05 was noted as statistically significant. Group 1 defined cancer as a contagious disease (p = 0.00025), they believed that early diagnosis was never possible (p = 0.042), all people with a diagnosis of cancer would certainly die (p = 0.044), and chemotherapy was not successful in a metastatic disease (p = 0.003) as compared to group 2. The rate of the students that believed gastric cancer screening was a part of the national screening policy was significantly more in group 1 than in group 2 (p = 0.00014). Group 2 had a higher anxiety level for themselves or their family members to become a cancer patient. Most of the students in both groups defined medical oncologists as warriors (57% in group 1 and 40% in group 2; p = 0.097), and cancer was reminding them of "death" (54% in group 1 and 48% in group 2; p = 0.102). This study suggested that oncology education was useful for the students' understanding of cancer and related issues; however, the level of oncology education should be improved in medical schools in Turkey. This would be helpful for medical doctors to cope with many aspects of cancer as a major health care problem in this country.


What does public health ethics tell (or not tell) us about intervening in non-communicable diseases?
Obesity has been described as pandemic and a public health crisis. It has been argued that concerted research efforts are needed to enhance our understanding and develop effective interventions for the complex and multiple dimensions of the health challenges posed by obesity. This would provide a secure evidence base in order to justify clinical interventions and public policy. This paper critically examines these claims through the examination of models of public health and public health ethics. I argue that the concept of an effective public health intervention is unclear and underdeveloped and, as a consequence, normative frameworks reliant on meeting the effectiveness criterion may miss morally salient dimensions of the problems. I conclude by arguing for the need to consider both an ecological model of public health and inclusion of a critical public health ethics perspective for an adequate account of the public health challenges posed by obesity.


Lack of phenotypic and evolutionary cross-resistance against parasitoids and pathogens in Drosophila melanogaster.
When organisms are attacked by multiple natural enemies, the evolution of a resistance mechanism to one natural enemy will be influenced by the degree of cross-resistance to another natural enemy. Cross-resistance can be positive, when a resistance mechanism against one natural enemy also offers resistance to another; or negative, in the form of a trade-off, when an increase in resistance against one natural enemy results in a decrease in resistance against another. Using Drosophila melanogaster, an important model system for the evolution of invertebrate immunity, we test for the existence of cross-resistance against parasites and pathogens, at both a phenotypic and evolutionary level. We used a field strain of D. melanogaster to test whether surviving parasitism by the parasitoid Asobara tabida has an effect on the resistance against Beauveria bassiana, an entomopathogenic fungus; and whether infection with the microsporidian Tubulinosema kingi has an effect on the resistance against A. tabida. We used lines selected for increased resistance to A. tabida to test whether increased parasitoid resistance has an effect on resistance against B. bassiana and T. kingi. We used lines selected for increased tolerance against B. bassiana to test whether increased fungal resistance has an effect on resistance against A. tabida. We found no positive cross-resistance or trade-offs in the resistance to parasites and pathogens. This is an important finding, given the use of D. melanogaster as a model system for the evolution of invertebrate immunity. The lack of any cross-resistance to parasites and pathogens, at both the phenotypic and the evolutionary level, suggests that evolution of resistance against one class of natural enemies is largely independent of evolution of resistance against the other.


First-Time Migration in Juvenile Common Cuckoos Documented by Satellite Tracking.
Being an obligate parasite, juvenile common cuckoos Cuculus canorus are thought to reach their African wintering grounds from Palearctic breeding grounds without guidance from experienced conspecifics but this has not been documented. We used satellite tracking to study naïve migrating common cuckoos. Juvenile cuckoos left breeding sites in Finland moving slowly and less consistently directed than adult cuckoos. Migration of the juveniles (N = 5) was initiated later than adults (N = 20), was directed toward the southwest-significantly different from the initial southeast direction of adults-and included strikingly long Baltic Sea crossings (N = 3). After initial migration of juvenile cuckoos toward Poland, the migration direction changed and proceeded due south, directly toward the winter grounds, as revealed by a single tag transmitting until arrival in Northwest Angola where northern adult cuckoos regularly winter. Compared to adults, the juvenile travelled straighter and faster, potentially correcting for wind drift along the route. That both migration route and timing differed from adults indicates that juvenile cuckoos are able to reach proper wintering grounds independently, guided only by their innate migration programme.


The effect of a probiotic strain (Lactobacillus acidophilus) on the plaque formation of oral Streptococci.
The objective of this study was to investigate the ability of biofilm formation among mutans and non mutans oral streptococci and to determine the effect of Lactobacillus acidophilus DSM 20079 as a probiotic strain on the adhesion of selected streptococcal strains on the surfaces. The sample comprised 40 isolates of oral streptococci from dental plaque and caries of volunteer persons. Streptococcus mutans ATCC35668 (no24) was as an standard strain. The probiotic strain was Lactobacillus acidophilus DSM 20079. The ability of biofilm formation was investigated with colorimetric method and the strongest isolates were selected. Then the effect of probiotic strain on the adhesion of streptococci isolates was determined in polystyrene microtiter plate simultaneously and 30 minutes before streptococci entrance to the system. The results showed that 42% of mutans streptococci were strongly adherent (SA) and in non mutans streptococci, only 23.5% of isolates were found strongly adherent. The strong biofilm forming bacterium isolated was Streptococcus mutans strain22. In the next step, in the presence of probiotic strain the streptococcal adhesion were reduced, and this reduction was non significantly stronger if the probiotic strain was inoculated to the system before the oral bacteria. The Lactobacillus acidophilus had more effect on adherence of mutans streptococci than non mutans streptococci with significant difference (p < 0.05). Adhesion reduction is likely due to bacterial interactions and colonization of adhesion sites with probiotic strain before the presence of streptococci. Adhesion reduction can be an effective way on decreasing cariogenic potential of oral streptococci.


A comparison of self-reported quality of life for an Australian haemodialysis and haemodiafiltration cohort.
Haemodiafiltration (HDF) has been widely studied for evidence of superior outcomes in comparison with conventional haemodialysis (HD), and there is increasing interest in determining if HDF confers any benefit in relation to quality of life. Studies have been conducted with randomized incident patients; however, little is known regarding HDF and quality of life for prevalent patients. This study examined and compared self-reported quality of life at two time points, 12 months apart in a cohort of satellite HD and HDF patients, using a disease specific questionnaire to determine if HDF conferred an advantage. A longitudinal study with a linear mixed-effect model measuring quality of life in a cohort of 171 patients (HD, n = 85, HDF, n = 86) in seven South Australian satellite dialysis centres. Factors associated with significant reduction across the Kidney Disease Quality Of Life™ domains measured were younger age (- 20 to - 29) and comorbid diabetes (- 4.8 to - 11.1). HDF was not associated with moderation of this reduction at either time point (P > 0.05). Baseline physical functioning was reported as very low (median 33.9) and further reduced at time point two. In addition, dialysing for more than 12 h per week in a satellite dialysis unit was associated with reduced quality of life in relation to the burden of kidney disease (- 13.69). This study has demonstrated that younger age and comorbid diabetes were responsible for a statistically significant reduction in quality of life, and HDF did not confer any advantage.


Rare EN1 Variants and Pediatric Bone Mass.
A recent whole-genome sequencing study in search of variation associated with adult areal bone mineral density (aBMD) identified rare variants near EN1, with markedly large effect sizes, and a common variant near SOX6. To understand the developmental effects of these loci, we sought to determine if they were associated with pediatric dual-energy X-ray absorptiometry-derived aBMD and bone mineral content (BMC) and if the associations were modified by sex. Our sample comprised 733 females and 685 males of European ancestry enrolled in the longitudinal Bone Mineral Density in Childhood Study (up to 7 annual study visits). Sex- and age-specific Z-scores, adjusted for height, were calculated for the total hip, femoral neck, spine, and distal radius. Total body less head (TBLH) BMC Z-scores were also calculated. The previously reported single nucleotide polymorphisms (SNPs) near EN1 and SOX6 were derived from our imputed data set. Linear mixed-effects models were used to test associations between each SNP and bone Z-scores, plus interactions with sex were explored. The rare T allele of lead EN1 SNP rs11692564 was associated with higher aBMD Z-score for total hip (beta = 0.62, p = 9.0 × 10(-4) ) and femoral neck (beta = 0.53, p = 0.010). In sex-stratified analyses, this variant was associated with higher bone Z-scores in females only, with the associations being strongest for total hip (sex interaction p = 1.9 × 10(-4) ; beta females = 0.86, p = 6.6 × 10(-6) ) and femoral neck (sex interaction p = 0.016; beta females = 0.73, p = 0.001). The common G allele of SOX6 SNP rs11024028 was associated with higher aBMD Z-score for total hip (beta = 0.12, p = 0.009), femoral neck (beta = 0.13, p = 0.003), and TBLH-BMC (beta = 0.09, p = 0.007); furthermore, this association strengthened in males in the sex-stratified analyses. Our findings reveal that rare genetic variation near EN1 and common variation near SOX6 operates in childhood and has implications for the lifelong risk of osteoporosis and fracture. The sex differences observed need to be independently replicated. © 2016 American Society for Bone and Mineral Research.


Etiology of the protein-energy wasting syndrome in chronic kidney disease: a consensus statement from the International Society of Renal Nutrition and Metabolism (ISRNM).
Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW.


Clinical added value of drugs: An empirical survey of French transparency committee opinions.
To identify criteria used by French health authorities to assess the clinical added value (ASMR) of drugs seeking reimbursement. We conducted a systematic review of the opinions of the transparency committee (TC) of the French national authority for health (HAS) between March, 2014 and October, 2016 in ten therapeutic areas. TC opinions content was coded and analysed using descriptive statistics and logistic models. The database comprised 160 opinion texts, which included ASMR assessments using a 5 level scale (1=highest ASMR 5=no ASMR). Main elements that were linked with ASMR 1,2,3,4 as compared to ASMR 5 were appraisal of the medical need, population size (<5000 patients), and clinical relevance of the evaluated results. The factors associated with ASMR 4 as compared to ASMR 1-3 were the safety profile and clinical relevance of the results. However, the factors associated with ASMR level varied according to the therapeutic area considered. The assessment of the drug ASMR conducted by the French transparency commission of the HAS appears to be at least in part determined by criteria (medical need, population size) which reflect the burden of the disease but not reflect the ASMR of the medicine assessed. Other criteria used for the assessment of ASMR are not clearly defined and depend on the therapeutic domain. The lack of sufficient clarity and consistency in assessment of ASMR complicate the decision making process for drug development. Moreover, this situation can be a barrier for a harmonized process of ASMR assessment at European level.


Sleepiness in patients with obstructive sleep apnoea - daytime course and impact of nocturnal respiratory events.
Obstructive sleep apnoea (OSA) is a condition leading to excessive daytime sleepiness. The aim of the study was a) to study course of daytime sleepiness in patients with OSA and b) to find the most important nocturnal polysomnography parameters influencing daytime sleepiness in OSA. The cohort consisted of forty-five patients (6 women, 39 men) diagnosed with OSA. All patients underwent polysomnography, Multiple Sleep Latency Test (MSLT) and rated subjectively their daytime tendency to sleep with the Epworth Sleepiness Scale. Sleep latency was significantly longer at 15:00 and at 17:00 hours compared to previous tests. A significant negative correlation was found between the mean of the MSLT sleep latency and a number of awakenings, the apnoea/hypopnoea index and oxygen desaturation index values. The study showed the sleep latency prolongation at 15:00 and 17:00 hours respectively and confirmed connection of excessive daytime sleepiness to fragmentation of nocturnal sleep and OSA severity.


Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias.
We have described a severe combined immunodeficiency (SCID) mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern, 14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.


Left main coronary artery thrombosis in a 19 year-old patient.
Left main coronary artery occlusion is a very rare entity that often results in death. It usually manifests as acute myocardial infarction (MI) with cardiogenic shock and fatal arrhythmias. Here, we report the case of a 19 year-old patient who presented with acute anterior MI secondary to left main coronary artery thrombosis. There were no classical risk factors for coronary heart disease in the anamnesis of the patient. Leukaemia was regarded to be the most probable predisposing condition in the patient.


Attachment, morphology and adherence of human endothelial cells to vascular prosthesis materials under the action of shear stress.
In an effort to improve the long-term patency of vascular prostheses several groups now advocate seeding autologous endothelial cells (ECs) onto the lumen of the vessel prior to implantation, a procedure that involves pre-treating the prosthesis material with fibrin, collagen and/or other matrix molecules to promote cell attachment and retention. In this study, we examined the degree to which human umbilical venous endothelial cells (HUVECs) adhered to three materials commonly used polymeric vascular prosthesis that had been coated with the same commercial extra cellular matrix proteins, and after exposure to fluid shear stresses representative of femoro-distal bypass in a cone-and-plate shearing device. We quantified cell number, area of coverage and degree of cell spreading using image analysis techniques. The response of cells that adhered to the surface of each material, and following exposure to fluid shear stress, depended on surface treatment, topology and cell type. Whereas collagen coating improved primary cellular adhesion and coverage significantly, the degree of spreading depended on the underlying surface structure and on the application of the shear stress. In some cases, fewer than 30% of cells remained on the surface after only 1-h exposure to physiological levels of shear stress. The proportion of the surface that was covered by cells also decreased, despite an increase in the degree to which individual cells spread on exposure to shear stress. Moreover, the behaviour of HUVECs was distinct from that of fibroblasts, in that the human ECs were able to adapt to their environment by spreading to a much greater extent in response to shear. The quality of HUVEC attachment, as measured by extent of cell coverage and resistance to fluid shear stress, was greatest on expanded polytetrafluoroethylene samples that had been impregnated with Type I/III collagen.


Genomic and genetic analysis of Bordetella bacteriophages encoding reverse transcriptase-mediated tropism-switching cassettes.
Liu et al. recently described a group of related temperate bacteriophages that infect Bordetella subspecies and undergo a unique template-dependent, reverse transcriptase-mediated tropism switching phenomenon (Liu et al., Science 295: 2091-2094, 2002). Tropism switching results from the introduction of single nucleotide substitutions at defined locations in the VR1 (variable region 1) segment of the mtd (major tropism determinant) gene, which determines specificity for receptors on host bacteria. In this report, we describe the complete nucleotide sequences of the 42.5- to 42.7-kb double-stranded DNA genomes of three related phage isolates and characterize two additional regions of variability. Forty-nine coding sequences were identified. Of these coding sequences, bbp36 contained VR2 (variable region 2), which is highly dynamic and consists of a variable number of identical 19-bp repeats separated by one of three 5-bp spacers, and bpm encodes a DNA adenine methylase with unusual site specificity and a homopolymer tract that functions as a hotspot for frameshift mutations. Morphological and sequence analysis suggests that these Bordetella phage are genetic hybrids of P22 and T7 family genomes, lending further support to the idea that regions encoding protein domains, single genes, or blocks of genes are readily exchanged between bacterial and phage genomes. Bordetella bacteriophages are capable of transducing genetic markers in vitro, and by using animal models, we demonstrated that lysogenic conversion can take place in the mouse respiratory tract during infection.


Empathy in osteopathic medical students: a cross-sectional analysis.
Empathy is fundamental to patient care. Research studies of allopathic medical students have found a statistically significant decrease in empathy levels by the third year. Levels of empathy in osteopathic medical students have not been evaluated to determine whether a similar decline occurs in this group. To determine whether there were differences according to year of schooling in mean levels of empathy among osteopathic medical students, as assessed with the Jefferson Scale of Physician Empathy-Student Version (JSPE-S), and, secondarily, to compare these measures of empathy in osteopathic medical students with those reported elsewhere for allopathic medical students. The JSPE-S was distributed to students during regularly scheduled classes at the end of the academic year at the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine in Stratford. Responses were anonymous. Data were analyzed by year in osteopathic medical school, sex, planned specialty, and ethnicity. Scores were compared with those of allopathic medical students reported elsewhere. Of the 415 respondents, 405 (98%) returned questionnaires with complete information, including 187 men (46%) and 218 women (54%). Of these respondents, 208 (51%) were white, 124 (31%) were Asian, and 73 (18%) were of another ethnicity. There were no statistically significant differences by year of schooling in respondents' sex, ethnicity, or specialty orientation and no statistically significant differences by year of schooling in the mean JSPE-S scores. Levels of empathy in osteopathic medical students were not found to decrease significantly by year of schooling, as reported in other studies for allopathic medical students. However, mean JSPE-S scores for first- and second-year osteopathic medical students were lower than those for first- and second-year allopathic medical students.


Diagnosis of essential thrombocythemia at platelet counts between 400 and 600x10(9)/L. Gruppo Italiano Malattie Mieloproliferative Croniche(GIMMC).
Diagnostic criteria for essential thrombocythemia (ET) remain essentially negative, that is, exclusion of other myeloproliferative diseases and causes of reactive thrombocytosis. A platelet count above 600x10(9)/L is still generally considered an absolute diagnostic criterion although new protocols for positive diagnostic criteria have recently been proposed, reducing the stringency of a definite platelet limit. This study demonstrates that a platelet count 600x10(9)/L is not a reliable diagnostic criterion for ET, especially in the early stages. An ongoing retrospective study by the GIMMC analyzed 2,316 ET patients diagnosed between 1986 and 1995. Of these 2,316 patients, diagnosed according to the PVSG criteria, 68 had a platelet count 600x10(9)/L and were analyzed separately; 37 out of 68 were excluded from this analysis because of a follow-up shorter than 2 years and/or because of treatment with myelosuppressive agents. The remaining 31 patients were the subjects of our study. After a median follow-up of 4.56 years (range 2-9.6 years) none of the 31 patients had a spontaneous decrease of platelets to the normal range. Transformation to a different chronic myeloproliferative disorders was never observed and no patient developed a condition known to produce reactive thrombocytosis. During follow-up, 23 patients (74%) were treated with anti-aggregating drugs, mainly aspirin. The disease did not evolve into acute leukemia in any patient, 1 had a thrombotic event and none presented hemorrhagic episodes. Median platelet count during follow-up was 534x10(9)/L (range 398-997x10(9)/L). Long term follow-up has documented that our 31 patients were correctly diagnosed as having ET, although platelet count was 600x10(9)/L. Our patients were probably in a early phase of their disease and following updated PVSG criteria would have been misdiagnosed leading to incomplete recognition of the natural history of the disease. Further, because an early diagnosis could also have a clinical relevance, our results outline the need for new criteria for the diagnosis of ET. The exclusion of patients with a platelet count between 400 and 600x10(9)/L may prevent patients, nevertheless at risk of vascular complications, from being treated.


Compliance of mothers following recommendations to breastfeed or withhold breast milk during rotavirus vaccination in North India: a randomized clinical trial.
Neutralizing antibodies in breast milk may adversely influence the immune response to live oral vaccines. Withholding breastfeeding around the time of vaccine administration has been suggested for improving vaccine performance. However, we do not know whether mothers find withholding breastfeeding around the time of vaccination acceptable and how they perceive this recommendation. In a clinical study designed to examine predictors of poor immune response to rotavirus vaccine in infants in India, Rotarix® was administered to infants at 6 and 10 weeks with other childhood vaccines. For the study, 400 mother-infant pairs were randomized into two groups in a 1:1 ratio. Mothers were either recommended to withhold breastfeeding or were encouraged to breastfeed half an hour before and after administration of Rotarix®. The mother-infant pairs were observed and the breastfeeding intervals were recorded during this period. Mothers were administered a questionnaire about their perception of the intervention after the infants received the second dose of Rotarix®. Almost 98% (391/400) of the infants received both doses of Rotarix®. Adherence to the recommendations was high in both groups. All mothers in the group who were asked to withhold breastfeeding did so, except one who breastfed her infant before the recommended time after the first dose of Rotarix®. Of the mothers, 4% (7/195) reported that the recommendation to withhold breastfeeding was difficult to follow. All mothers in this group reported that they would withhold breastfeeding at the time of vaccination if they were asked to by a health-care provider. Only one mother responded that withholding breastfeeding would be a reason for not giving rotavirus vaccine to her infant. Withholding breastfeeding half an hour before and after vaccination appears to be acceptable to mothers in this setting. If withholding breastfeeding produces an improvement in the performance of the vaccine, it could be used to increase the public health impact of rotavirus immunization. Clinical Trial Registry, India (CTRI/2012/10/003057), Clinicaltrials.gov (NCT01700127).Date of Registration: Clinical Trial Registry, India: 28 September 2012, Clinicaltrials.gov: 3 October 2012.


Virtual screen to NMR (VS2NMR): Discovery of fragment hits for the CBP bromodomain.
Overexpression of the CREB-binding protein (CBP), a bromodomain-containing transcription coactivator involved in a variety of cellular processes, has been observed in several types of cancer with a correlation to aggressiveness. We have screened a library of nearly 1500 fragments by high-throughput docking into the CBP bromodomain followed by binding energy evaluation using a force field with electrostatic solvation. Twenty of the 39 fragments selected by virtual screening are positive in one or more ligand-observed nuclear magnetic resonance (NMR) experiments. Four crystal structures of the CBP bromodomain in complex with in silico screening hits validate the pose predicted by docking. Thus, the success ratio of the high-throughput docking procedure is 50% or 10% if one considers the validation by ligand-observed NMR spectroscopy or X-ray crystallography, respectively. Compounds 1 and 3 show favorable ligand efficiency in two different in vitro binding assays. The structure of the CBP bromodomain in the complex with the brominated pyrrole 1 suggests fragment growing by Suzuki coupling.


Expressions of epidermal growth factor family and its receptor in hepatocellular carcinoma cell lines: relationship to cell proliferation.
In 6 HCC cell lines, clear expressions of EGFR and TGF-alpha were found in flow cytometry, while expressions of EGF, HB-EGF and AR were quite low. TGF-alpha secretion into culture supernatants became measurable when TPA 0.5 microM was added. TPA accelerated the proliferation of KYN-3 cells, and anti-TGF-alpha neutralizing antibody suppressed this proliferation in a dose-dependent manner. Addition of exogenous TGF-alpha, EGF, AR, or HB-EGF with heparin accelerated cell proliferation. In non-stimulated cultures, cell proliferation was suppressed by anti-EGFR neutralizing antibody, but not by the antibodies for EGF, TGF-alpha, AR and HB-EGF. HCC may possess a paracrine system regulated by these 4 ligands, and an autocrine system, under a certain condition, via TGF-alpha and EGFR.


Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart.
Whole body insulin resistance and diabetes are risk factors for cardiovascular diseases, yet little is known about insulin resistance in the diabetic heart. The aim of this work was to define the insulin response in hearts of the Goto-Kakizaki (GK) rat, a polygenic model of spontaneous type 2 diabetes. We measured D[2-3H]glucose uptake before and after insulin stimulation, plus initial steps of the insulin signaling pathway after insulin infusion via the caudal vena cava in hearts from the male Wistar and spontaneously diabetic GK rats. Despite normal basal D[2-3H]glucose uptake, insulin-stimulated glucose uptake was 50% (p<0.03) lower in GK rat hearts compared with their Wistar controls. Total GLUT4 protein was depleted by 28% (p<0.01) in GK rat hearts. We found 31% (p<0.0001) and 38% (p<0.001) decreased protein levels of insulin receptor beta (IRbeta)-subunit and insulin receptor substrate-1 (IRS-1), respectively, in GK rat hearts with 37% (p<0.02) and 45% (p<0.01) lower insulin-stimulated tyrosine phosphorylation of these proteins. Owing to the decreased IRS-1 protein levels, GK rat hearts had a 41% (p<0.0001) decrease in insulin-stimulated IRS-1 protein association with the p85 subunit of phosphatidylinositol 3-kinase, despite normal phosphatidylinositol 3-kinase protein expression. Insulin-stimulated serine phosphorylation of protein kinase B was the same in all hearts, as was protein kinase B expression. We conclude that decreased insulin receptor beta, IRS-1 and GLUT4 proteins are associated with insulin resistance in type 2 diabetic rat hearts.


An importance of carbohydrate ingestion for the expression of the effect of alpha-glucosidase inhibitor in NIDDM.
To examine the usefulness of alpha-glucosidase inhibitors in glycemic control of patients with NIDDM. The involvement of carbohydrate ingestion in manifestation of the effects of alpha-glucosidase inhibitors was also investigated. A total of 41 patients hospitalized with NIDDM (22 patients receiving sulfonylurea and 19 receiving insulin therapy) were given alpha-glucosidase inhibitors during the period when their blood glucose levels were well controlled. They were followed for 3 weeks as inpatients and for an additional 6 months as outpatients. They were retrospectively divided into two groups according to the percentage of carbohydrates in all sources of calories during outpatient management: the < 50% group and the > 50% group. Between these two groups, we compared circadian variation in blood glucose levels, HbA1c, and urine C-peptide. Treatment with alpha-glucosidase inhibitors during the hospital stay markedly improved circadian variation in blood glucose levels and HbA1c and decreased urine C-peptide in both groups. While HbA1c returned to its pretreatment level at 6 months after the treatment in the < 50% group, HbA1c had further improved in the > 50% group at 6 months. alpha-Glucosidase inhibitors are useful for glycemic control in patients with NIDDM and the percentage of carbohydrate in all calorie sources is an important factor for the expression of their effects.


Fabrication of photonic devices directly written within glass using a femtosecond laser.
We present a novel method for three-dimensional optical splitter that have U-grooves, which are used for fiber alignment, within a fused silica glass using near-IR femtosecond laser pulses. The fiber aligned optical splitter has a low insertion loss, less than 4 dB, including an intrinsic splitting loss of 3 dB and excess loss due to the passive alignment of a single-mode fiber. The output field pattern is presented, demonstrating the splitting ratio of the optical splitter is approximately 1:1. Finally, we demonstrate the utility of the femtosecond laser writing of periodic patterns by fabricating the submicron line and dot patterns inside the silica glass, which is applicable to 3-D optical memory.


The Drosophila mutation turnip has pleiotropic behavioral effects and does not specifically affect learning.
The Drosophila mutant turnip (tur) was isolated on the basis of its poor performance in an olfactory learning task, and also has a reduction in protein kinase C (PKC) activity. PKC has been found in the nervous systems of a wide range of organisms and appears to have an important role in learning and memory-related processes. Unfortunately, previous reports documenting the learning defect of tur lacked the controls required to assess the origins of the poor performance of the mutant. We have analyzed the effects of the tur mutation on both associative and nonassociative learning as well as on PKC activity. Additionally, the effects of the mutation on the task-relevant sensorimotor abilities of the flies were assessed. Although we were able to replicate previous behavioral and biochemical results obtained with tur, we discovered that the tur mutation also affected response to electric shock and caused a drastic reduction in the locomotor ability of the flies. Because locomotion is an essential component of the learning assays, this result makes it impossible to conclude that tur specifically affects learning and demonstrates the crucial importance of sensorimotor controls in conditioning experiments.


Global Adoption of Genetically Modified (GM) Crops: Challenges for the Public Sector.
Advances in biotechnology continue to drive the development of a wide range of insect-protected, herbicide-tolerant, stress-tolerant, and nutritionally enhanced genetically modified (GM) crops, yet societal and public policy considerations may slow their commercialization. Such restrictions may disproportionately affect developing countries, as well as smaller entrepreneurial and public sector initiatives. The 2014 IUPAC International Congress of Pesticide Chemistry (San Francisco, CA, USA; August 2014) included a symposium on "Challenges Associated with Global Adoption of Agricultural Biotechnology" to review current obstacles in promoting GM crops. Challenges identified by symposium presenters included (i) poor public understanding of GM technology and the need for enhanced communication strategies, (ii) nonharmonized and prescriptive regulatory requirements, and (iii) limited experience with regulations and product development within some public sector programs. The need for holistic resistance management programs to enable the most effective use of insect-protected crops was also a point of emphasis. This paper provides details on the symposium discussion and provides background information that can be used in support of further adoption of beneficial GM crops. Overall, it emphasizes that global adoption of modern agricultural biotechnology has not only provided benefits to growers and consumers but has great potential to provide solutions to an increasing global population and diminishing agricultural land. This potential will be realized by continued scientific innovation, harmonized regulatory systems, and broader communication of the benefits of the high-yielding, disease-resistant, and nutritionally enhanced crops attainable through modern biotechnology.


IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression.
Cathepsin S is a cysteine protease with potent endoproteolytic activity and a broad pH profile. Cathepsin S activity is essential for complete processing of the MHC class II-associated invariant chain within B cells and dendritic cells, and may also be important in extracellular matrix degradation in atherosclerosis and emphysema. Unique among cysteine proteases, cathepsin S activity is up-regulated by IFN-gamma. Given its importance, we sought to elucidate the pathway by which IFN-gamma increases cathepsin S expression. Our data demonstrate that the cathepsin S promoter contains an IFN-stimulated response element (ISRE) that is critical for IFN-gamma-induced gene transcription in a cell line derived from type II alveolar epithelial (A549) cells. IFN response factor (IRF)-2 derived from A549 nuclear extracts associates with the ISRE oligonucleotide in gel shift assays, but is quickly replaced by IRF-1 following stimulation with IFN-gamma. The time course of IRF-1/ISRE complex formation correlates with increased levels of IRF-1 protein and cathepsin S mRNA. Overexpression of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity in A549 cells. Furthermore, overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T epithelial cells. Finally, freshly isolated bone marrow cells from IRF-1(-/-) mice fail to up-regulate cathepsin S activity in response to IFN-gamma. Thus, IRF-1 is the critical transcriptional mediator of IFN-gamma-dependent cathepsin S activation. These data elucidate a new pathway by which IRF-1 may affect MHC class II processing and presentation.


An Environmental Scan of Academic Emergency Medicine at the 17 Canadian Medical Schools: Why Does this Matter to Emergency Physicians?
We sought to conduct a major objective of the CAEP Academic Section, an environmental scan of the academic emergency medicine programs across the 17 Canadian medical schools. We developed an 84-question questionnaire, which was distributed to academic heads. The responses were validated by phone by the lead author to ensure that the questions were answered completely and consistently. Details of pediatric emergency medicine units were excluded from the scan. At eight of 17 universities, emergency medicine has full departmental status and at two it has no official academic status. Canadian academic emergency medicine is practiced at 46 major teaching hospitals and 13 specialized pediatric hospitals. Another 69 Canadian hospital EDs regularly take clinical clerks and emergency medicine residents. There are 31 full professors of emergency medicine in Canada. Teaching programs are strong with clerkships offered at 16/17 universities, CCFP(EM) programs at 17/17, and RCPSC residency programs at 14/17. Fourteen sites have at least one physician with a Master's degree in education. There are 55 clinical researchers with salary support at 13 universities. Sixteen sites have published peer-reviewed papers in the past five years, ranging from four to 235 per site. Annual budgets range from $200,000 to $5,900,000. This comprehensive review of academic activities in emergency medicine across Canada identifies areas of strengths as well as opportunities for improvement. CAEP and the Academic Section hope we can ultimately improve ED patient care by sharing best academic practices and becoming better teachers, educators, and researchers.


Genetic diversity of arabica coffee (Coffea arabica L.) in Nicaragua as estimated by simple sequence repeat markers.
Coffea arabica L. (arabica coffee), the only tetraploid species in the genus Coffea, represents the majority of the world's coffee production and has a significant contribution to Nicaragua's economy. The present paper was conducted to determine the genetic diversity of arabica coffee in Nicaragua for its conservation and breeding values. Twenty-six populations that represent eight varieties in Nicaragua were investigated using simple sequence repeat (SSR) markers. A total of 24 alleles were obtained from the 12 loci investigated across 260 individual plants. The total Nei's gene diversity (H(T)) and the within-population gene diversity (H(S)) were 0.35 and 0.29, respectively, which is comparable with that previously reported from other countries and regions. Among the varieties, the highest diversity was recorded in the variety Catimor. Analysis of variance (AMOVA) revealed that about 87% of the total genetic variation was found within populations and the remaining 13% differentiate the populations (F(ST) = 0.13; P < 0.001). The variation among the varieties was also significant. The genetic variation in Nicaraguan coffee is significant enough to be used in the breeding programs, and most of this variation can be conserved through ex situ conservation of a low number of populations from each variety.


Exploring the Progressive Use of Performance Enhancing Substances by High-Performance Athletes.
Background: Given implications associated with the use of performance-enhancing substances (PESs), stakeholders must remain informed about usage precipitants and anticipate conditions signaling athlete vulnerability to hazardous exposures. Objectives: To gain deeper qualitative insight into high-level athlete PES usage; explore the variables leading them to escalate their PES use regimens; reveal PES experiences during their careers and, unlike other studies, not to focus exclusively on "doping" as measured by the use of WADA-banned substances. Methods: A macro life course-based framework from which the data could emerge through a thematic coding analysis was utilized. Sixteen narrative life course histories of recently retired high-performance athletes report on the factors impelling their escalation in PES use, including for some, the first use of banned PES. Results: Informant reports, thematically coded, reveal performance maximization urgency to be a central factor in escalating PES use, driven by four variables: Requirements, Opportunities, Influencers and Outcomes. These variables each comprise two key components that stimulate an urgency ecosystem affecting an athlete's proximity to an escalation threshold. Conclusions/Importance: Such a comprehensive investigation of PES use precipitants has not previously been undertaken. Advances in PES use were instantiated by a substantive, sometimes radical and often sudden increase in urgency to improve performance related to output requirements, specific demands, knowledge and access, timing windows, the competitive landscape, loyalty to coaches, efficiency expectations and likelihood of detection. This study informs incremental models of doping, the use of which is encouraged in order to analyze life course narratives to better understand athlete behaviors.


Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain.
The ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans.


Comparison of the regulation of carboxypeptidase E and prolactin in GH4C1 cells, a rat pituitary cell line.
The treatment of GH4C1 cells, a prolactin-producing rat anterior pituitary cell line, with estradiol (1 nM), insulin (300 nM) and epidermal growth factor (10 nM) has been previously shown to substantially increase both the intracellular level of prolactin, as well as the number of secretory granules. In this study, we examined the effect of this treatment on levels of carboxypeptidase E (CPE), a prohormone-processing enzyme. GH4C1 cells contain CPE mRNA and enzymatic activity. The secretion of both prolactin and CPE activity from GH4C1 cells is stimulated 10-fold by 50 mM KCl and 2- to 3-fold by 100 nM thyrotropin-releasing hormone, suggesting that these two proteins are contained in secretory granules. Treatment of GH4C1 cells with estradiol, insulin, and epidermal growth factor causes an increase in the intracellular level of CPE to approximately 2-fold of control values. This change is much smaller than the change in the level of prolactin: intracellular prolactin is increased 140-fold by the treatment. Kinetic analysis of the CPE activity indicates that the treatment does not alter the Km of substrate hydrolysis, with the change in activity the result of an increase in apparent Vmax. Northern blot analysis indicates that the level of CPE mRNA is not influenced (less than 10%) by the treatment, whereas the level of prolactin mRNA is increased 9-fold. These results indicate that CPE is not coordinately regulated with prolactin in the GH4C1 cell line, although some regulation of CPE activity does occur.


Enhancing Crop Domestication Through Genomic Selection, a Case Study of Intermediate Wheatgrass.
Perennial grains could simultaneously provide food for humans and a host of ecosystem services, including reduced erosion, minimized nitrate leaching, and increased carbon capture. Yet most of the world's food and feed is supplied by annual grains. Efforts to domesticate intermediate wheatgrass (Thinopyrumn intermedium, IWG) as a perennial grain crop have been ongoing since the 1980's. Currently, there are several breeding programs within North America and Europe working toward developing IWG into a viable crop. As new breeding efforts are established to provide a widely adapted crop, questions of how genomic and phenotypic data can be used among sites and breeding programs have emerged. Utilizing five cycles of breeding data that span 8 years and two breeding programs, University of Minnesota, St. Paul, MN, and The Land Institute, Salina, KS, we developed genomic selection (GS) models to predict IWG traits. Seven traits were evaluated with free-threshing seed, seed mass, and non-shattering being considered domestication traits while agronomic traits included spike yield, spikelets per inflorescence, plant height, and spike length. We used 6,199 genets - unique, heterozygous, individual plants - that had been profiled with genotyping-by-sequencing, resulting in 23,495 SNP markers to develop GS models. Within cycles, the predictive ability of GS was high, ranging from 0.11 to 0.97. Across-cycle predictions were generally much lower, ranging from -0.22 to 0.76. The prediction ability for domestication traits was higher than agronomic traits, with non-shattering and free threshing prediction abilities ranging from 0.27 to 0.75 whereas spike yield had prediction abilities ranging from -0.22 to 0.26. These results suggest that progress to reduce shattering and increase the percent free-threshing grain can be made irrespective of the location and breeding program. While site-specific programs may be required for agronomic traits, synergies can be achieved in rapidly improving key domestication traits for IWG. As other species are targeted for domestication, these results will aid in rapidly domesticating new crops.


3-Arm star pyrene-functional PMMAs for efficient exfoliation of graphite in chloroform: fabrication of graphene-reinforced fibrous veils.
3-Arm PMMAs end-functionalized by pyrene were designed as dispersing/stabilizing agents for the liquid-phase exfoliation of graphite in low-boiling point solvents like chloroform. The synthetic procedure comprised ARGET ATRP controlled polymerization, click chemistry and the quaternization reaction of triazole, ensuring tailor-made, well-defined pyrene-functional star PMMAs. Among a series of different pyrene-functional macromolecular topologies, the (PMMA-py2)3 proved the most efficient exfoliation agent giving relatively high graphene concentration (0.36 mg ml-1) at exceptionally low polymer/graphite mass ratio (mP/mGF = 0.003) and short sonication time (3 h). A 5-cycle iterative procedure relying on the redispersion of the sediment was developed yielding CG = 1.29 mg ml-1 with 14.8% exfoliation yield, under the favorable conditions of 10.5 h total shear mixing/tip sonication time and overall mP/mGF ratio as low as 0.15. In parallel, all-atom molecular dynamics simulations were conducted which helped understand the mechanism by which pyrene-functional macromolecular topologies act as efficient dispersing agents of graphene. Finally the G@(PMMA-Py)3 hybrids were well dispersed into the PMMA matrix by electrospinning to fabricate graphene-based nanocomposite fibrous veils. These graphene/polymer nanocomposites exhibited enhanced stiffness and strength by a factor of 4.4 with 1.5 wt% graphene hybrids as nanofillers.


Ras signaling is required for serum-induced hyphal differentiation in Candida albicans.
Serum induces Candida albicans to make a rapid morphological change from the yeast cell form to hyphae. Contrary to the previous reports, we found that serum albumin does not play a critical role in this morphological change. Instead, a filtrate (molecular mass, <1 kDa) devoid of serum albumin induces hyphae. To study genes controlling this response, we have isolated the RAS1 gene from C. albicans by complementation. The Candida Ras1 protein, like Ras1 and Ras2 of Saccharomyces cerevisiae, has a long C-terminal extension. Although RAS1 appears to be the only RAS gene present in the C. albicans genome, strains homozygous for a deletion of RAS1 (ras1-2/ras1-3) are viable. The Candida ras1-2/ras1-3 mutant fails to form germ tubes and hyphae in response to serum or to a serum filtrate but does form pseudohyphae. Moreover, strains expressing the dominant active RAS1(V13) allele manifest enhanced hyphal growth, whereas those expressing a dominant negative RAS1(A16) allele show reduced hyphal growth. These data show that low-molecular-weight molecules in serum induce hyphal differentiation in C. albicans through a Ras-mediated signal transduction pathway.


Postural electromyographic responses in the arm and leg following galvanic vestibular stimulation in man.
Application of a small (around 1 mA), constant electric current between the mastoid processes (galvanic stimulation) of a standing subject produces enhanced body sway in the approximate direction of the ear behind which the anode is placed. We examined the electromyographic (EMG) responses evoked by such stimulation in the soleus and in the triceps brachii muscles. For soleus, subjects stood erect, with their eyes closed, leaning slightly forward. The head was turned approximately 90 degrees to the right or left relative to the feet. In averaged records (n = 40), current pulses of 25 ms or longer modulated the EMG in a biphasic manner: a small early component (latency 62 +/- 2.4 ms, mean +/- SEM) was followed by a larger late component (latency 115 +/- 5.2 ms) of opposite sign, which was appropriate to produce the observed body sway. The early component produced no measurable body movement. Lengthening the duration of the stimulus pulse from 25 to 400 ms prolonged the late component of the response but had little effect on the early component. Short- and long-latency EMG responses were also evoked in the triceps brachii muscle if subjects stood on a transversely pivoted platform and had to use the muscle to maintain their balance in the anteroposterior plane by holding a fixed handle placed by the side of their hip. The latency of the early component was 41 +/- 2.6 ms; the latency of the late component was 138 +/- 4.3 ms and was again of appropriate sign for producing the observed body sway. Galvanic stimulation evoked no comparable responses in either triceps brachii or soleus muscles if these muscles were not being used posturally.(ABSTRACT TRUNCATED AT 250 WORDS)


Semantically linking molecular entities in literature through entity relationships.
Text mining tools have gained popularity to process the vast amount of available research articles in the biomedical literature. It is crucial that such tools extract information with a sufficient level of detail to be applicable in real life scenarios. Studies of mining non-causal molecular relations attribute to this goal by formally identifying the relations between genes, promoters, complexes and various other molecular entities found in text. More importantly, these studies help to enhance integration of text mining results with database facts. We describe, compare and evaluate two frameworks developed for the prediction of non-causal or 'entity' relations (REL) between gene symbols and domain terms. For the corresponding REL challenge of the BioNLP Shared Task of 2011, these systems ranked first (57.7% F-score) and second (41.6% F-score). In this paper, we investigate the performance discrepancy of 16 percentage points by benchmarking on a related and more extensive dataset, analysing the contribution of both the term detection and relation extraction modules. We further construct a hybrid system combining the two frameworks and experiment with intersection and union combinations, achieving respectively high-precision and high-recall results. Finally, we highlight extremely high-performance results (F-score > 90%) obtained for the specific subclass of embedded entity relations that are essential for integrating text mining predictions with database facts. The results from this study will enable us in the near future to annotate semantic relations between molecular entities in the entire scientific literature available through PubMed. The recent release of the EVEX dataset, containing biomolecular event predictions for millions of PubMed articles, is an interesting and exciting opportunity to overlay these entity relations with event predictions on a literature-wide scale.


Influence of Cropping Systems on Stem Rot (Sclerotium rolfsii), Meloidogyne arenaria, and the Nematode Antagonist Pasteuria penetrans in Peanut.
The effect of crop rotation (main plots) and pesticide treatment (subplots) on stem rot (Sclerotium rolfsii), Meloidogyne arenaria, and the nematode antagonist Pasteuria penetrans was determined in a field experiment. The field site was naturally infested with all three organisms. Peanut (P) was rotated with 2 years of either cotton (Ct), corn (C), or bahiagrass (B). The pesticide treatments for the peanut crop were aldicarb (31 g a.i. per 100-m row), flutolanil (1.7 kg a.i./ha), aldicarb + flutolanil, and a control without either pesticide. Populations of M. arenaria were lower in peanut in the Ct-Ct-P than in P-P-P, C-C-P, or B-B-P plots and tended to be lower in plots treated with aldicarb. Abundance of P. penetrans endospores was highest in the P-P-P plots, intermediate in the B-B-P rotations, lowest in all other rotations, and was unaffected by aldicarb. The high endospore densities in the P-P-P plots may have contributed to the uncharacteristically low nematode populations in the monoculture. Incidence of stem rot in peanut was lowest in treatments with flutolanil, intermediate in the control, and highest in treatments with aldicarb alone. The greater canopy cover in aldicarb-treated plots may have created a conducive environment for S. rolfsii infection.


Effects of the addition of subarachnoid clonidine to the anesthetic solution of sufentanil and hyperbaric or hypobaric bupivacaine for labor analgesia.
The addition of subarachnoid clonidine (alpha-agonist) prolongs the analgesia produced by the combination of sufentanil and isobaric bupivacaine in combined labor analgesia(1). The objective of this study was to compare the quality of analgesia and the prevalence of side effects after the addition of subarachnoid clonidine to the anesthetic solution in labor analgesia. After approval by the Ethics Commission, 22 pregnant women in labor were randomly assigned to the subarachnoid administration of either 2.5 mg of 0.5% hyperbaric bupivacaine (CLON/HYPER Group; n = 11) or 2.5 mg of 0.5% isobaric bupivacaine (CLON/ISO Group; n = 11) associated with 2.5 microg of sufentanil and 30 microg of clonidine. Pain, evaluated by the Visual Analogue Scale, heart rate, and mean arterial pressure were assessed every 5 minutes during the first 15 minutes, and then every 15 minutes afterwards until delivery. The prevalence of side effects (nausea, vomiting, pruritus, and sedation) was evaluated. The study was terminated whenever the patient needed supplemental epidural analgesia (pain > 3) or upon delivery of the fetus. The Student t test, Chi-square test, Fisher exact test, and two-way ANOVA for repeated measurements were used in the statistical analysis and a p < 0.05 was considered significant. Anthropometric data, duration of analgesia (70.9 +/- 32.9 vs. 85.4 +/- 39.5), heart rate, and the incidence of pruritus, sedation, nausea, and vomiting were similar in both groups. Mean arterial pressure was significantly lower in the CLON/ISO Group than in the CLON/HYPER Group at 15, 30, and 45 minutes (p < 0.05). Under the conditions of the present study, the association of a small dose of clonidine (30 microg) with sufentanil caused a higher incidence of hypotension when the isobaric solution of the local anesthetic was used. For all other side effects, both hyperbaric and isobaric solutions showed similar behavior.


High-resolution genotyping of Chlamydia trachomatis from recurrent urogenital infections.
A method for Chlamydia trachomatis restriction fragment length polymorphism (RFLP) analysis and complete sequencing of omp1 was developed for use on samples collected at home, and results were compared. Genotyping by sequencing was superior to RFLP analysis. The omp1 gene in 31 clinical strains harbored few mutations compared to the same gene in ATCC reference strains. Follow-up samples obtained during a 24-week period from 31 patients showed recurrence with the same genotype in five cases and a new genotype in one case.


Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise.
Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.


Putting evidence into practice: evidence-based interventions for oral agents for cancer.
The limited evidence available suggests that adherence to oral agents for cancer is a significant clinical problem and may have a substantial impact on treatment success or failure. Adherence is a difficult issue among patients who are very sick with a life-threatening disease who often must adhere to complex treatment protocols independently at home. This article aims to identify effective interventions for the promotion, treatment, and management of adherence to oral agents for cancer and to synthesize the literature for use in clinical practice. As part of the Oncology Nursing Society (ONS) Putting Evidence Into Practice (PEP) initiative, a comprehensive examination of the current literature was conducted to identify effective interventions for patients prescribed oral agents for cancer. The ONS PEP weight-of-evidence classification schema levels of evidence were used to categorize interventions to assist nurses in identifying strategies that are effective at improving adherence. The majority of evidence found was conducted in conditions other than cancer; therefore, research is needed to identify whether these interventions are effective at promoting adherence in patients with cancer.


Two Episodes of Trigeminocardiac Reflex During a Pan facial Fracture Surgery, a Rare Phenomenon - Case Report and Review of Literature.
Trigeminocardiac reflex is a sudden physiologic response due to mechanical manipulation of any of the branches of trigeminal nerve. Trigeminocardiac reflex occurs due to pressure effect or stretching of trigeminal nerve which causes fall in blood pressure and decrease in heart rate. In this reflex arc, the trigeminal nerve serves as afferent pathway and vagus nerve, which is cardio inhibitory in nature, serves as efferent pathway. Two episodes of trigeminocardiac reflex during maxillofacial trauma surgery is not a common phenomenon. The present case report describes a case of 40-year-old male patient, diagnosed with pan facial fracture in which two episodes of trigeminocardiac reflex were seen intraoperatively during fracture reduction and fixation of left zygomaticomaxillary complex fracture and inferior orbital rim fracture. Intraoperative management of trigeminocardiac reflex was done by withholding the stimulus and administration of atropine.


Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion.
Chemerin, a chemoattractant protein, acts via a G-protein coupled chemokine receptor, i.e. Chemokine like Receptor 1/ChemR23; levels of which are elevated in pro-inflammatory states such as obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM patients are at high risk of developing cardiovascular disorders such as atherosclerosis. We have reported that chemerin induces human endothelial cell angiogenesis and since dysregulated angiogenesis and endothelial dysfunction are hallmarks of vascular disease; we sought to determine the effects of chemerin on monocyte-endothelial adhesion, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a critical pro-inflammatory transcription factor. Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Chemerin induced NF-κB activation via the MAPK and PI3K/Akt pathways. Western blot analyses and monocyte-endothelial adhesion assay showed that chemerin increased endothelial cell adhesion molecule expression and secretion, namely E-selectin (Endothelial Selectin), VCAM-1 (Vascular Cell Adhesion Molecule-1) and ICAM-1 (Intracellular Adhesion Molecule-1), leading to enhancement of monocyte-endothelial adhesion. Additionally, we showed a synergistic response of the pro-inflammatory mediator, Interleukin-1β with chemerin induced effects. Chemerin plays an important role in endothelial inflammation, as it induces monocyte-endothelial adhesion, a critical step in the development of atherosclerosis.


Development of a core outcome set for behavioural weight management programmes for adults with overweight and obesity: protocol for obtaining expert consensus using Delphi methodology.
Weight management interventions in research studies and in clinical practice differ in length, advice, frequency of meetings, staff and cost. Very few real-world programmes have published patient-related outcomes, and those that have published used different ways of reporting the information, making it impossible to compare interventions and further develop the evidence base. Developing a core outcome set for behavioural weight management programmes (BWMPs) for adults with overweight and obesity will allow different BWMPs to be compared and reveal which interventions work best for which members of the population. An expert group, comprised of 40 people who work in, refer to, or attend BWMPs for adults with overweight and obesity, will be asked to decide which outcomes services should report. An online Delphi process will be employed to help the group reach consensus as to which outcomes should be measured and reported, and which definitions/instruments should be used in order to do so. The first stage of the Delphi process (three rounds of questionnaires) will focus on outcomes while the second stage (three additional rounds of questionnaires) will focus on definition/instrument selection. Ethical approval for this study has been received from the University of Glasgow College of Medical, Veterinary and Life Sciences Ethics Committee. With regard to disseminating results, a report will be submitted to our funding body, the Chief Scientist Office of the Scottish Government Health Department. In addition, early findings will be shared with Public Health England and Health Scotland, and results communicated via conference presentations, peer review publication and our institutions' social media platforms.


Association study of AMP-activated protein kinase subunit genes in polycystic ovary syndrome.
To examine the genes for AMP-activated protein kinase (AMPK) subunits alpha2 (PRKAA2) and gamma3 (PRKAG3) as candidates for polycystic ovary syndrome (PCOS) and its component traits. A total of 287 white PCOS women were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham and 187 white control subjects were recruited from the surrounding community. Seven PRKAA2 single nucleotide polymorphisms (SNPs) and four PRKAG3 SNPs were genotyped in PCOS cases and controls. Genotyping and association analysis were performed at Cedars-Sinai Medical Center. Nominal associations of PRKAA2 variants with insulin-related traits and the PRKAG3 Pro71Ala variant with PCOS were not statistically significant after multiple testing correction. Among PCOS patients, there were no associations between variants in AMPK subunit genes and androgenic or reproductive traits. Variants in genes for AMPKalpha2 and AMPKgamma3 were not associated with PCOS or its component traits. Our evidence does not demonstrate that AMPK is a major genetic risk factor for PCOS.


Recent trends in outpatient antibiotic use in children.
The goal of this study was to determine changes in antibiotic-dispensing rates among children in 3 health plans located in New England [A], the Mountain West [B], and the Midwest [C] regions of the United States. Pharmacy and outpatient claims from September 2000 to August 2010 were used to calculate rates of antibiotic dispensing per person-year for children aged 3 months to 18 years. Differences in rates by year, diagnosis, and health plan were tested by using Poisson regression. The data were analyzed to determine whether there was a change in the rate of decline over time. Antibiotic use in the 3- to <24-month age group varied at baseline according to health plan (A: 2.27, B: 1.40, C: 2.23 antibiotics per person-year; P < .001). The downward trend in antibiotic dispensing slowed, stabilized, or reversed during this 10-year period. In the 3- to <24-month age group, we observed 5.0%, 9.3%, and 7.2% annual declines early in the decade in the 3 plans, respectively. These dropped to 2.4%, 2.1%, and 0.5% annual declines by the end of the decade. Third-generation cephalosporin use for otitis media increased 1.6-, 15-, and 5.5-fold in plans A, B, and C in young children. Similar attenuation of decline in antibiotic use and increases in use of broad-spectrum agents were seen in other age groups. Antibiotic dispensing for children may have reached a new plateau. Along with identifying best practices in low-prescribing areas, decreasing broad-spectrum use for particular conditions should be a continuing focus of intervention efforts.


Transcription and replication of the influenza a virus genome.
The genome of influenza A virus consists of eight segments of negative-strand viral RNA (vRNA). During the replication cycle of the virus, the genomic vRNA is transcribed into positive-strand mRNA and complementary RNA (cRNA) in the cell nucleus. The promoter for the synthesis of mRNA molecules is located in a partially double-stranded RNA structure formed by the 5'- and 3'-terminal sequences of genomic vRNA segments. The virus encoded RNA-dependent RNA polymerase complex has to interact with both ends of the vRNA in order to generate capped RNA primers by endonucleolytic cleavage of cellular pre-mRNAs for the initiation of viral mRNA synthesis. Conserved sequence elements in the 5'-end, e.g. a polymerase binding site and a U(5-7) sequence are required for polyadenylation of virus-specific mRNAs. Polyadenylation occurs by reiterative copying of the U(5-7) sequence by the viral RNA polymerase, which is bound to the 5'end of the vRNA template. The U(5-7) sequence acts directly as a template for the poly(A)-tail. During the replication cycle of the virus, a "switch" from mRNA to cRNA synthesis occurs, but the mechanism by which this switch occurs remains unclear. The viral nucleoprotein and its interaction with the polymerase proteins and vRNA might play a role in this process. In contrast to transcription, the process of replication--the synthesis of cRNA and vRNA, which are known to occur in the absence of primers--is poorly understood.


Re-examining environmental correlates of Plasmodium falciparum malaria endemicity: a data-intensive variable selection approach.
Malaria risk maps play an increasingly important role in disease control planning, implementation, and evaluation. The construction of these maps using modern geospatial techniques relies on covariate grids: continuous surfaces quantifying environmental factors that partially explain spatial heterogeneity in malaria endemicity. Although crucial, past variable selection processes for this purpose have often been subjective and ad-hoc, with many covariates used in modeling with little quantitative justification. This research consists of an extensive covariate construction and selection process for predicting Plasmodium falciparum parasite rates (PfPR) in Africa for years 2000-2012. First, a literature review was conducted to establish a comprehensive list of covariates used for malaria mapping. Second, a library of covariate data was assembled to reflect this list, a process that included the construction of multiple, temporally dynamic datasets. Third, the resulting set of covariates was leveraged to create more than 50 million possible covariate terms via factorial combinations of different spatial and temporal aggregations, transformations, and pairwise interactions. Fourth, the expanded set of covariates was reduced via successive selection criteria to yield a robust covariate subset that was assessed using an out-of-sample validation approach. The final covariate subset included predominately dynamic covariates and it substantially out-performed earlier sets used by the Malaria Atlas Project (MAP) for creating global malaria risk maps, with the pseudo-R(2) value for the out-of-sample validation increasing from 0.43 to 0.52. Dynamic covariates improved the model, with 17 of the 20 new covariates consisting of monthly or annual products, but the selected covariates were typically interaction terms that included both dynamic and synoptic datasets. Thus the interplay between normal (i.e., long-term averages) and immediate conditions may be key for characterizing environmental controls on parasite rate. This analysis represents the first effort to systematically audit covariate utility for malaria mapping and then derive an objective, empirically based set of environmental covariates for modeling PfPR. The new covariates produce more reliable representations of malaria risk patterns and how they are changing through time, and these covariates will be used to characterize spatially and temporally varying environmental conditions affecting PfPR within a geostatistical-modeling framework, thus building upon previous research by MAP that produced global malaria maps for 2007 and 2010.


Effects of daily treatment with parathyroid hormone 1-84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys.
Treatment with parathyroid hormone 1-84 (PTH) or teriparatide increases osteonal remodeling and decreases bone mineral density (BMD) at cortical (Ct) bone sites but may also increase bone size. Decreases in BMD and increases in size exert opposing effects on bone strength. In adult ovariectomized (OVX) rhesus monkeys, we assessed the effects of daily PTH treatment (5, 10 or 25 microg/kg) for 16 months on BMD at the radial, tibial and femoral diaphyses, and on biomechanical properties (3-point bending) of radial cortical bone and the femoral diaphysis. PTH treatment did not affect areal BMD measured by dual-energy X-ray absorptiometry at the tibial diaphysis but caused a rapid, dose-related decrease at the distal radial diaphysis. Peripheral quantitative computed tomography at the radial and femoral diaphyses confirmed a significant PTH dose-related decrease in volumetric Ct.BMD caused primarily by increased cortical area. Significant increases in cortical thickness were the result of nonsignificant increases in periosteal length and decreases in endocortical length. Histomorphometry revealed increased endocortical bone formation at the tibial diaphysis and rib, higher Haversian remodeling at the rib and increased cortical porosity at the rib and tibia. Biomechanical testing at the femoral diaphysis showed that PTH treatment had no effect on peak load, but significantly decreased stiffness and increased work-to-failure (the energy required to break the bone). Similar changes occurred in radial cortical beams but only stiffness was changed significantly. Thus, PTH treatment of OVX rhesus monkeys decreased BMD and stiffness of cortical bone but did not affect peak load, likely because of increased bone size. However, PTH treatment increased the energy required to break the femur making it more resistant to fracture.


TRF requirements for in vitro PFC responses to SRBC and R36a. I. TRF is distinct from IL 2 but indistinguishable from polyclonal BCSF.
In vitro PFC responses to the thymus-independent (TI) antigen Streptococcus pneumoniae R36a require T cell replacing factor(s) (TRF). This requirement for TRF is as significant as for the thymus-dependent (TD) antigen SRBC. TRF is shown to be distinct from IL 2 by the following observations: 1) culture supernatants from the cloned T cell line L2, collected over an 8-day period after allogeneic stimulation, transiently contain IL 2 activity but maintain high levels of TRF activity throughout 192 hr; 2) L2V, a variant subclone of L2, produces much higher levels of TRF activity than the parental line but no detectable IL 2 activity; 3) the addition of IL2+, TRF- supernatants from the T cell hybridoma FS6-14.13 does not affect the L2V SF-driven PFC responses to R36a or SRBC; and 4) the addition of contaminating T cells to cultures containing T cell-depleted spleen cells, L2V SF, and antigen does not affect the PFC response. TRF does appear to be indistinguishable from polyclonal B cell stimulating factor (BCSF), which stimulates polyclonal PFC responses in the absence of antigen, mitogen, or anti-Ig. The TRF and BCSF activities of L2V SF could not be separated by ion-exchange, hydrophobic-interaction, and gel-filtration chromatography. TRF and BCSF have an apparent m.w. of approximately 40,000.


Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.
Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.


Advertising health: the case for counter-ads.
Public service advertisements have been used by many in hopes of "selling" good health behaviors. But selling good behavior--even if it could be done more effectively--is not the best goal for using mass media to prevent health problems. Personal behavior is only part of what determines health status. Social conditions and the physical environment are important determinants of health that are usually ignored by health promotion advertising. Public service advertising may be doing more harm than good if it is diverting attention from more effective socially based health promotion strategies. Counter-ads are one communications strategy that could be used to promote a broader responsibility for rectifying health problems. In the tradition of advocacy advertising directly promoting policy rather than products, counter-ads promote views consistent with a public health perspective. Counter-ads set the agenda for health issues, conferring status on policy-oriented strategies for addressing health problems. The primary purpose of counter-ads is to challenge the dominant view that public health problems reflect personal health habits. They are controversial because they place health issues in a social and political context. Advertising strategies for health promotion range over a spectrum from individually oriented public service advertising to socially oriented counter-advertising. The recent anti-tobacco campaign from the California Department of Health Services represents advertisements across the spectrum. Counter-ads that focus on a politically controversial definition for health problems are an appropriate and necessary alternative to public service advertising.


Minimally invasive transforaminal lumbar interbody fusion with expandable versus static interbody devices: radiographic assessment of sagittal segmental and pelvic parameters.
OBJECTIVE Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been adopted as an alternative technique to hasten recovery and minimize postoperative morbidity. Advances in instrumentation technologies and operative techniques have evolved to maximize patient outcomes as well as radiographic results. The development of expandable interbody devices allows a surgeon to perform MIS-TLIF with minimal tissue disruption. However, sagittal segmental and pelvic radiographic outcomes after MIS-TLIF with expandable interbody devices are not well characterized. The object of this study is to evaluate the radiographic sagittal lumbar segmental and pelvic parameter outcomes of MIS-TLIF performed using an expandable interbody device. METHODS A retrospective review of MIS-TLIFs performed between 2014 and 2016 at a high-volume center was performed. Radiographic measurements were performed on lateral radiographs before and after MIS-TLIF with static or expandable interbody devices. Radiographic measurements included disc height, foraminal height, fused disc angle, lumbar lordosis, pelvic incidence, sacral slope, and pelvic tilt. Mismatch between pelvic incidence and lumbar lordosis were calculated for each radiograph. RESULTS A total of 48 MIS-TLIFs were performed, predominantly at the L4-5 level, in 44 patients. MIS-TLIF with an expandable interbody device led to a greater and more sustained increase in disc height when compared with static interbody devices. Foraminal height increased after MIS-TLIF with expandable but not with static interbody devices. MIS-TLIF with expandable interbody devices increased index-level segmental lordosis more than with static interbody devices. The increase in segmental lordosis was sustained in the patients with expandable interbody devices but not in patients with static interbody devices. For patients with a collapsed disc space, MIS-TLIF with an expandable interbody device provided superior and longer-lasting increases in disc height, foraminal height, and index-level segmental lordosis than in comparison with patients with static interbody devices. Using an expandable interbody device improved the Oswestry Disability Index scores more than using a static interbody device, and both disc height and segmental lordosis were correlated with improved clinical outcome. Lumbar MIS-TLIF with expandable or static interbody devices had no effect on overall lumbar lordosis, pelvic parameters, or pelvic incidence-lumbar lordosis mismatch. CONCLUSIONS Performing MIS-TLIF with an expandable interbody device led to a greater and longer-lasting restoration of disc height, foraminal height, and index-level segmental lordosis than MIS-TLIF with a static interbody device, especially for patients with a collapsed disc space. However, neither technique had any effect on radiographic pelvic parameters.


Latent Print Proficiency Testing: An Examination of Test Respondents, Test-Taking Procedures, and Test Characteristics.
Proficiency testing is a key component of quality assurance programs within crime laboratories and can help improve laboratory practices. However, current proficiency testing procedures contain significant limitations and can be misinterpreted by examiners and court personnel (Garrett & Mitchell, 2018). To evaluate some of these limitations, we surveyed latent print examiners (n = 198) after they completed a Collaborative Testing Services, Inc. proficiency test. Additionally, we evaluated test performance and used a quality metric algorithm to evaluate the quality of test prints. Results do not suggest that respondents are dissimilar to the broader examiner population, although they may engage in different behaviors when completing tests versus casework. Findings show that proficiency testing contains prints of high quality and is perceived as both relatively easy and representative of casework. The test discriminated between inexperienced and experienced respondents, and verification procedures were largely ineffective in reducing errors. Objective quality metrics may provide a path forward to improving proficiency testing in a measurable manner.


Taking a Stand: An Untapped Strategy to Reduce Waterpipe Smoking in Adolescents.
Waterpipe use amongst adolescents is on the rise globally. Thus, there is a need to understand adolescents 'attitudes towards and perceptions of waterpipe use in order to develop specific interventions against this form of tobacco use. Focus group interviews were conducted among 37 Swedish adolescents (14 boys and 23 girls) from grades 10 to 12. Waterpipe users and nonusers were interviewed separately, with two groups each for users and nonusers. Interviews were audiotaped, transcribed, and thematically analyzed using content analysis. Six themes emerged including taking a stand, weighing the risks, Lack of knowledge, Social context, Waterpipe new and unknown, and Family influence. Taking a stand was about being able to stand up for one's owns views rather than giving in to peer pressure to smoke waterpipe. Participants feared harming others via secondhand smoke and expressed criticism of the tobacco industry. Participants considered the health consequences and feared addiction. Lack of knowledge concerning health effects of waterpipe smoking due to the unavailability of credible information was also reported. Waterpipe smoking was considered a social event carried out in the company of friends. Perceived as novel and fun, waterpipe was smoked out of curiosity. Parents' and siblings' smoking behaviors influenced adolescent waterpipe use. Adolescents reported lacking information about the possible health effects of waterpipe smoking and that gaining such knowledge would make it easier for them to take a stand and refuse smoking waterpipe. Prevention strategies should focus on providing adolescents with factual information about the dangers of waterpipe use.


A genome sequence from a modern human skull over 45,000 years old from Zlatý kůň in Czechia.
Modern humans expanded into Eurasia more than 40,000 years ago following their dispersal out of Africa. These Eurasians carried ~2-3% Neanderthal ancestry in their genomes, originating from admixture with Neanderthals that took place sometime between 50,000 and 60,000 years ago, probably in the Middle East. In Europe, the modern human expansion preceded the disappearance of Neanderthals from the fossil record by 3,000-5,000 years. The genetic makeup of the first Europeans who colonized the continent more than 40,000 years ago remains poorly understood since few specimens have been studied. Here, we analyse a genome generated from the skull of a female individual from Zlatý kůň, Czechia. We found that she belonged to a population that appears to have contributed genetically neither to later Europeans nor to Asians. Her genome carries ~3% Neanderthal ancestry, similar to those of other Upper Palaeolithic hunter-gatherers. However, the lengths of the Neanderthal segments are longer than those observed in the currently oldest modern human genome of the ~45,000-year-old Ust'-Ishim individual from Siberia, suggesting that this individual from Zlatý kůň is one of the earliest Eurasian inhabitants following the expansion out of Africa.