Helicobacter pylori and its eradication in rosacea.
Rosacea is a common condition of unknown etiology usually accompanied by gastrointestinal symptoms and favorably responding to the treatment with antibiotics. This study was designed to examine the prevalence of gastric Helicobacter pylori (Hp) infection verified by 13C-UTB-test, CLO, Hp culture and serology (IgG) in patients with rosacea. Gastroduodenoscopy was combined with pentagastrin secretory test and antral and fundic biopsy samples were taken for histological evaluation (the Sydney system). Blood samples were also taken for the determination of plasma gastrin using RIA and plasma interleukin (IL)-8 and tumor necrosis factor alpha (TNFalpha) using ELISA. This study was performed in 60 patients, 31-72 year old, with visible papules and pustules associated with erythema and flushing on the face and on 60 age- and gender-matched patients without any skin diseases but with similar as in rosacea gastrointestinal symptoms but without endoscopic changes in gastroduodenal mucosa (non-ulcer dyspepsia - NUD). The Hp prevalence in rosacea patients was about 88 % as compared to 65% in control NUD patients. Among rosacea patients, 67% were cytotoxin associated gene A (CagA) positive, while in NUD patients only 32% were CagA positive. Rosacea patients showed gastritis with activity of about 2.1 in antrum and 0.9 in the corpus of the stomach while those with NUD only mild gastritis with activity of approximately 1.0) confined to the antrum only. Following initial examination, typical 1 wk anti-Hp therapy including omeprazole (20 mg bd.), clarithromycin (500 mg bd.) and metronidazol (500 mg bd.) was carried out. After eradication, 51 out of 53 treated rosacea patients became Hp negative. Within 2-4 weeks, the symptoms of rosacea disappeared in 51 patients, markedly declined in 1 and remained unchanged in 1 other subject. A dramatic reduction in activity of gastritis (to 0.3 in antrum and to 0.1 in corpus) was observed. Basal plasma gastrin decreased from 48 +/- 5 pM before to 17+/-3 pM after eradication, while pentagastrin-induced maximal (MAO) declined, respectively, from about 16.6 +/- 4.2 to 8.5 +/- 1.8 mmol/h. Plasma TNFalpha and IL-8 were reduced after the therapy by 72% and 65%, respectively. We conclude that: 1) Rosacea is a disorder with various gastrointestinal symptoms closely related to gastritis, especially involving the antrum mucosa, with Hp expressing cagA in the majority of cases and elevated plasma levels of TNFalpha and IL-8; 2) The eradication of Hp leads to a dramatic improvement of symptoms of rosacea and reduction in related gastrointestinal symptoms, gastritis, hypergastrinemia and gastric acid secretion; and 3) Rosacea could be considered as one of the major extragastric symptoms of Hp infection probably mediated by Hp-related cytotoxins and cytokines.


Structure and age-dependent development of the turkey liver: a comparative study of a highly selected meat-type and a wild-type turkey line.
In this study the macroscopic and microscopic structure of the liver of a fast growing, meat-type turkey line (British United turkeys BUT Big 6, n=25) and a wild-type turkey line (Wild Canadian turkey, n=48) were compared at the age of 4, 8, 12, 16, and 20 wk. Because the growth plates of long bones were still detectable in the 20-week-old wild-type turkeys, indicating immaturity, a group of 8 wild-type turkeys at the age of 24 wk was included in the original scope of the study. Over the term of the study, the body and liver weights of birds from the meat-type turkey line increased at a faster rate than those of the wild-type turkey line. However, the relative liver weight of the meat-type turkeys declined (from 2.7 to 0.9%) to a greater extent than that of the wild-type turkeys (from 2.8 to 1.9%), suggesting a mismatch in development between muscle weights and liver weights of the meat-type turkeys. Signs of high levels of fat storage in the liver were detected in both lines but were greater in the wild-type turkey line, suggesting a better feed conversion by the extreme-genotype birds i.e., meat-type birds. For the first time, this study presents morphologic data on the structure and arrangement of the lymphatic tissue within the healthy turkey liver, describing two different types of lymphatic aggregations within the liver parenchyma, i.e., aggregations with and without fibrous capsules. Despite differences during development, both adult meat-type and adult wild-type turkeys had similar numbers of lymphatic aggregations.


Metabolic response of the cerebral cortex following gentle sleep deprivation and modafinil administration.
The main energy reserve of the brain is glycogen, which is almost exclusively localized in astrocytes. We previously reported that cerebral expression of certain genes related to glycogen metabolism changed following instrumental sleep deprivation in mice. Here, we extended our investigations to another set of genes related to glycogen and glucose metabolism. We also compared the effect of instrumentally and pharmacologically induced prolonged wakefulness, followed (or not) by 3 hours of sleep recovery, on the expression of genes related to brain energy metabolism. Sleep deprivation for 6-7 hours. Animal sleep research laboratory. Adults OF1 mice. Wakefulness was maintained by "gentle sleep deprivation" method (GSD) or by administration of the wakefulness-promoting drug modafinil (MOD) (200 mg/kg i.p.). Levels of mRNAs encoding proteins related to energy metabolism were measured by quantitative real-time PCR in the cerebral cortex. The mRNAs encoding protein targeting to glycogen (PTG) and the glial glucose transporter were significantly increased following both procedures used to prolong wakefulness. Glycogenin mRNA levels were increased only after GSD, while neuronal glucose transporter mRNA only after MOD. These effects were reversed after sleep recovery. A significant enhancement of glycogen synthase activity without any changes in glycogen levels was observed in both conditions. These results indicate the existence of a metabolic adaptation of astrocytes aimed at maintaining brain energy homeostasis during the sleep-wake cycle.


Temperament and dominance relate to feeding behaviour and activity in beef cattle: implications for performance and methane emissions.
In beef cattle, feeding behaviour and activity are associated with feed efficiency and methane (CH4) emissions. This study aimed to understand the underlying traits responsible for the contribution of cattle behaviour to individual differences in feed efficiency, performance and CH4 emissions. A total of 84 steers (530±114 kg BW) of two different breeds (crossbreed Charolais and Luing) were used. The experiment was a 2×2×3 factorial design with breed, basal diets (concentrate v. mixed) and dietary treatments (no additive, calcium nitrate or rapeseed cake) as the main factors. The individual dry matter intake (DMI; kg) was recorded daily and the BW was measured weekly over a 56-day period. Ultrasound fat depth was measured on day 56. Based on the previous data, the indexes average daily gain, food conversion and residual feed intake (RFI) were calculated. The frequency of meals, the duration per visit and the time spent feeding per day were taken as feeding behaviour measures. Daily activity was measured using the number of steps, the number of standing bouts and the time standing per day. Agonistic interactions (including the number of contacts, aggressive interactions, and displacements per day) between steers at the feeders were assessed as indicators of dominance. Temperament was assessed using the crush score test (which measures restlessness when restrained) and the flight speed on release from restraint. Statistical analysis was performed using multivariate regression models. Steers that spent more time eating showed better feed efficiency (P=0.039), which can be due to greater secretion of saliva. Feeding time was longer with the mixed diet (P<0.001), Luings (P=0.009) and dominant steers (P=0.032). Higher activity (more steps) in the pen was associated with poorer RFI, possibly because of higher energy expenditure for muscle activity. Frequent meals contributed to a reduction in CH4 emissions per kg DMI. The meal frequency was higher with a mixed diet (P<0.001) and increased in more temperamental (P=0.003) and dominant (P=0.017) steers. In addition, feed intake was lower (P=0.032) in more temperamental steers. This study reveals that efficiency increases with a longer feeding time and CH4 emissions decrease with more frequent meals. As dominant steers eat more frequently and for longer, a reduction in competition at the feeder would improve both feed efficiency and CH4 emissions. Feed efficiency can also be improved through a reduction in activity. Selection for calmer cattle would reduce activity and increase feed intake, which may improve feed efficiency and promote growth, respectively.


Regulation of galanin gene expression in gonadotropin-releasing hormone neurons during the estrous cycle of the rat.
Galanin is colocalized with GnRH in neurons of the hypothalamus and basal forebrain of female rats, and this neuropeptide may play a role in the generation of the midcycle surge of gonadotropin secretion. We tested the hypothesis that galanin gene expression in GnRH cells increases during proestrus. To accomplish this, we killed groups of adult female rats at 1200 and 1800 h on the day of proestrus as well as at 1800 h on the day of estrus and used double labeling in situ hybridization and image analysis to estimate and compare the levels of galanin mRNA in cells coexpressing GnRH mRNA. GnRH mRNA was detected with an antisense cRNA probe labeled with the hapten digoxigenin, while the galanin cRNA probe was labeled with 35S and detected by autoradiography. There was no significant difference in the total number of GnRH cells identified in each animal in any of the different groups in any experiment. The relative number of silver grains over these cells, reflecting galanin mRNA content in GnRH neurons (identified by their purple color), was counted with a computerized image analysis system. In an initial experiment, we observed a 2-fold (P < 0.03) higher galanin mRNA signal level in the animals killed at 1800 h than in those killed at 1200 h on the day of proestrus. Animals killed at 1800 h on the day of estrus had galanin mRNA signal levels that were not statistically different from those in the proestrous 1800 h group, indicating that the increase in galanin mRNA at proestrus is maintained for at least 24 h. Galanin mRNA levels in GnRH neurons returned to basal levels equivalent to those in the proestrous 1200 h group by 1000 h on diestrous day 1. In conjunction with the studies of galanin gene expression in GnRH neurons, we compared the relative cellular contents of GnRH mRNA among the same groups. Here, we used single labeling isotopic in situ hybridization for GnRH mRNA and computerized image analysis to count the resulting silver grains. We could detect no difference in GnRH mRNA signal levels (proestrus, 1200 h vs. proestrus, 1800 h vs. estrus, 1800 h). In a final experiment, we investigated the possible role of estrogen in the induction of galanin mRNA expression at proestrus by comparing relative galanin mRNA contents in GnRH neurons among groups of ovariectomized, intact (diestrous day 1), and ovariectomized 17 beta-estradiol-replaced female rats.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of flow intermittency and pharmaceutical exposure on the structure and metabolism of stream biofilms.
Increasing concentrations of pharmaceutical compounds occur in many rivers, but their environmental risk remains poorly studied in stream biofilms. Flow intermittency shapes the structure and functions of ecosystems, and may enhance their sensitivity to toxicants. This study evaluates the effects of a long-term exposure of biofilm communities to a mixture of pharmaceutical compounds at environmental concentrations on biofilm bioaccumulation capacity, the structure and metabolic processes of algae and bacteria communities, and how their potential effects were enhanced or not by the occurrence of flow intermittency. To assess the interaction between those two stressors, an experiment with artificial streams was performed. Stream biofilms were exposed to a mixture of pharmaceuticals, as well as to a short period of flow intermittency. Results indicate that biofilms were negatively affected by pharmaceuticals. The algal biomass and taxa richness decreased and unicellular green algae relatively increased. The structure of the bacterial (based on denaturing gradient gel electrophoresis of amplified 16S rRNA genes) changed and showed a reduction of the operational taxonomic units (OTUs) richness. Exposed biofilms showed higher rates of metabolic processes, such as primary production and community respiration, attributed to pharmaceuticals stimulated an increase of green algae and heterotrophs, respectively. Flow intermittency modulated the effects of chemicals on natural communities. The algal community became more sensitive to short-term exposure of pharmaceuticals (lower EC50 value) when exposed to water intermittency, indicating cumulative effects between the two assessed stressors. In contrast to algae, the bacterial community became less sensitive to short-term exposure of pharmaceuticals (higher EC50) when exposed to water intermittency, indicating co-tolerance phenomena. According to the observed effects, the environmental risk of pharmaceuticals in nature is high, but different depending on the flow regime, as well as the target organisms (autotrophs vs heterotrophs).


Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.
Highly pathogenic avian influenza (HPAI) H5N1 viruses cause severe infection in chickens at near complete mortality, but corresponding infection in ducks is typically mild or asymptomatic. To understand the underlying molecular differences in host response, primary chicken and duck lung cells, infected with two HPAI H5N1 viruses and a low pathogenicity avian influenza (LPAI) H2N3 virus, were subjected to RNA expression profiling. Chicken cells but not duck cells showed highly elevated immune and pro-inflammatory responses following HPAI virus infection. HPAI H5N1 virus challenge studies in chickens and ducks corroborated the in vitro findings. To try to determine the underlying mechanisms, we investigated the role of signal transducer and activator of transcription-3 (STAT-3) in mediating pro-inflammatory response to HPAIV infection in chicken and duck cells. We found that STAT-3 expression was down-regulated in chickens but was up-regulated or unaffected in ducks in vitro and in vivo following H5N1 virus infection. Low basal STAT-3 expression in chicken cells was completely inhibited by H5N1 virus infection. By contrast, constitutively active STAT-3 detected in duck cells was unaffected by H5N1 virus infection. Transient constitutively-active STAT-3 transfection in chicken cells significantly reduced pro-inflammatory response to H5N1 virus infection; on the other hand, chemical inhibition of STAT-3 activation in duck cells increased pro-inflammatory gene expression following H5N1 virus infection. Collectively, we propose that elevated pro-inflammatory response in chickens is a major pathogenicity factor of HPAI H5N1 virus infection, mediated in part by the inhibition of STAT-3.


Liposarcomas in dogs: 56 cases (1989-2000).
To determine the biological behavior of liposarcomas in dogs and identify clinical signs, the effect of treatment on survival time, and potential prognostic factors. Retrospective study. 56 dogs with histologically confirmed liposarcoma. Information was obtained on signalment, tumor size, location of the tumor, stage of disease, remission duration, overall survival time, cause of death, type of surgery (incisional biopsy, marginal excision, or wide excision), and any additional treatments given. Surgery consisted of incisional biopsy in 6 dogs, marginal excision in 34, and wide excision in 16. Twenty-five dogs had histologic evidence of tumor cells at the surgical margins and 28 did not (status of the margins was unknown in 3 dogs). Twelve of 43 dogs had local recurrence. Median survival time was 694 days, and the only factor significantly associated with survival time was type of surgery performed. Median survival times were 1,188, 649, and 183 days, respectively, for dogs that underwent wide excision, marginal excision, and incisional biopsy. Factors that were not found to be significantly associated with survival time included tumor size, status of the margins, tumor location, and histologic subtype. Results suggest that in dogs, liposarcomas are locally invasive neoplasms that rarely metastasize and occur primarily in appendicular or axial locations and that wide excision is preferred to marginal excision when feasible.


Interaction of chitin/chitosan with salivary and other epithelial cells-An overview.
Chitin and its deacetylated form, chitosan, have been widely used for tissue engineering of both epithelial and mesenchymal tissues. Epithelial cells characterised by their sheet-like tight cellular arrangement and polarised nature, constitute a major component in various organs and play a variety of roles including protection, secretion and maintenance of tissue homeostasis. Regeneration of damaged epithelial tissues has been studied using biomaterials such as chitin, chitosan, hyaluronan, gelatin and alginate. Chitin and chitosan are known to promote proliferation of various embryonic and adult epithelial cells. However it is not clearly understood how this activity is achieved or what are the mechanisms involved in the chitin/chitosan driven proliferation of epithelial cells. Mechanistic understanding of influence of chitin/chitosan on epithelial cells will guide us to develop more targeted regenerative scaffold/hydrogel systems. Therefore, current review attempts to elicit a mechanistic insight into how chitin and chitosan interact with salivary, mammary, skin, nasal, lung, intestinal and bladder epithelial cells.


MTHFR gene polymorphisms in bladder cancer in the Turkish population.
Bladder cancer is the 9th most common cancer and is responsible for malignancy related death all on the world. Folate and folate related enzyme polymorphisms related to the cancer risk. The methylene tethrahydrofolate reductase (MTHFR) enzyme is folate related and association of bladder cancer and MTHFR gene. Our purpose was to assess the prevalence of MTHFR gene 677 CT and 1298 AC polymorphisms and Bladder cancer in Turkey. We intended that bladder cancer patients and controls and we used the Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. The MTHFR gene C677T and A1298C polymorphisms were associated with an increased risk of bladder cancer in our population (For the MTHFR gene C677T polymorphism and A1298C polymorphism; p=0.036<0.05; p=0.278>0.05 respectively). Consequently, the MTHFR gene C677T polymorphism augments the risk of bladder cancer in Turkey.


[Measurement of morbidity attended in an integrated health care organization].
Understanding the quality, costs and outcomes of healthcare services requires precise determination of the morbidity in a population. Measurement of morbidity in a population and its association with the services provided remains to be performed. The aim of this article was to present our experience of using clinical risk groups (CRGs) to measure morbidity in an integrated healthcare organization (IHO). We studied the population attended by an IHO in a county (approximately 120,000 patients) from 2002 to 2005. CRGs were used to measure morbidity. A descriptive analysis was performed of the population's distribution in CRG categories and utilization rates. One or more chronic diseases was found in 15.5% of the population, significant acute illness was found in 9%, minor chronic diseases was found in 7% and very severe diseases was found in 0.5%. Between 2002 and 2005, the number of individuals with chronic disease increased by 8%. The burden of illness increased with age. However, at all ages, at least 40% of the population remained healthy. Comorbidity in chronic illnesses was a crucial factor in explaining healthcare resource utilization. The CRG grouping system aids analysis at different levels for clinical administration. Due to its composition, this system allows better understanding of the use, costs and quality of the set of services received by a population.


Wavelet basis function neural networks for sequential learning.
In this letter, we develop the wavelet basis function neural networks (WBFNNs). It is analogous to radial basis function neural networks (RBFNNs) and to wavelet neural networks (WNNs). In WBFNNs, both the scaling function and the wavelet function of a multiresolution approximation (MRA) are adopted as the basis for approximating functions. A sequential learning algorithm for WBFNNs is presented and compared to the sequential learning algorithm of RBFNNs. Experimental results show that WBFNNs have better generalization property and require shorter training time than RBFNNs.


Regulation of ERK (extracellular signal regulated kinase), part of the neurotrophin signal transduction cascade, in the rat mesolimbic dopamine system by chronic exposure to morphine or cocaine.
Local infusion of brain-derived neurotrophic factor (BDNF) into the ventral tegmental area (VTA) can prevent and reverse the ability of chronic morphine or cocaine exposure to induce tyrosine hydroxylase (TH) in this brain region. The present study examined a possible role for extracellular signal regulated kinases (ERKs), the major effector for BDNF and related neurotrophins, in morphine and cocaine action in the VTA. Chronic, but not acute, administration of morphine or cocaine increased ERK catalytic activity specifically in the VTA. This increase in ERK activity reflected an increase in the state of phosphorylation of ERK, with no change in levels of total ERK immunoreactivity. Chronic infusions of BDNF into the VTA reduced total ERK immunoreactivity with no change in ERK activity, and also blocked the morphine-induced increase in ERK activity. These results suggest that chronic BDNF elicits a compensatory increase in the phosphorylation of the remaining ERK molecules and thereby prevents any additional increase in response to drug exposure. Such a role for ERK in morphine action was demnostrated directly by chronically infusing antisense oligonucleotides to ERK1 into the VTA. This treatment selectively reduced levels of ERK1 immunoreactivity in a sequence-specific manner without detectable toxicity. Intra-VTA infusion of ERK1 antisense oligonucleotides mimicked the effects of chronic BDNF infusions on ERK immunoreactivity, ERK activity, and TH immunoreactivity in the VTA under both control and morphine-treated conditions. The chronic morphine-induced increases in ERK activity and TH expression in the VTA also were blocked by local infusion of NMDA glutamate receptor antagonists, suggesting a role for glutamate in mediating these drug effects. Together, these findings support a scheme whereby chronic, systemic administration of morphine or cocaine leads to a sustained increase in ERK phosphorylation state and activity in the VTA, which, in turn, contributes to drug-induced increases in TH, and perhaps other drug-induced adaptations, elicited selectively in this brain region.


Effect of telomere length on prognosis in men with acute coronary syndrome.
Telomere length is related to cellular aging and cardiovascular disease. Nevertheless, the specific role of cellular aging in this process is still unclear. The aim of this report was to analyze the prognostic value of telomere length in men admitted for acute coronary syndrome. Telomere length was measured by quantitative polymerase chain reaction in peripheral blood leukocytes of 203 men classified into 2 groups: those aged 50 to 75 years and those >75 years. Clinical follow-up had been done for >600 days, and a prognostic combined event was defined. In men aged 50 to 75 years, we found a statistically significant worse prognosis in patients with short telomeres (log-rank: 5.22, p <0.05) but not in men >75 years (log-rank: 0.01, p = 0.91). Cox analysis confirmed short telomeres in men aged 50 to 75 years as an independent prognostic risk factor. In conclusion, telomere length is a good predictor of cardiovascular prognosis in men admitted for acute coronary syndrome, but this relation depends on the chronological age of the population studied.


Helicobacter pylori: new developments and treatments.
The authors highlight new developments in research on Helicobacter pylori. There is now consensus that all patients with newly diagnosed or recurrent duodenal or gastric ulcers who have a positive test result for H. pylori should be treated for the infection. Patients presenting with complications of ulcers, such as bleeding, should also be treated. H. pylori has recently been classified as a definite human carcinogen by the International Agency for Research on Cancer. In treatment, new combination regimens, consisting of 3 or 4 different drugs, cure the infection in more than 80% of patients. Currently, the best combinations are: (1) omeprazole (or another proton-pump inhibitor), clarithromycin and metronidazole, (2) omeprazole (or another proton-pump inhibitor), clarithromycin and amoxicillin, (3) bismuth subsalicylate, tetracycline and metronidazole, and (4) omeprazole, bismuth subsalicylate, tetracycline and metronidazole.


Empowering conservation practice with efficient and economical genotyping from poor quality samples.
Moderate- to high-density genotyping (100 + SNPs) is widely used to determine and measure individual identity, relatedness, fitness, population structure and migration in wild populations.However, these important tools are difficult to apply when high-quality genetic material is unavailable. Most genomic tools are developed for high-quality DNA sources from laboratory or medical settings. As a result, most genetic data from market or field settings is limited to easily amplified mitochondrial DNA or a few microsatellites.To enable genotyping in conservation contexts, we used next-generation sequencing of multiplex PCR products from very low-quality DNA extracted from faeces, hair and cooked samples. We demonstrated utility and wide-ranging potential application in endangered wild tigers and tracking commercial trade in Caribbean queen conch.We genotyped 100 SNPs from degraded tiger samples to identify individuals, discern close relatives and detect population differentiation. Co-occurring carnivores do not amplify (e.g. Indian wild dog/dhole) or are monomorphic (e.g. leopard). Sixty-two SNPs from conch fritters and field-collected samples were used to test relatedness and detect population structure.We provide proof of concept for a rapid, simple, cost-effective and scalable method (for both samples and number of loci), a framework that can be applied to other conservation scenarios previously limited by low-quality DNA samples. These approaches provide a critical advance for wildlife monitoring and forensics, open the door to field-ready testing, and will strengthen the use of science in policy decisions and wildlife trade.


Spatiotemporal analysis of air pollution and asthma patient visits in Taipei, Taiwan.
Buffer analyses have shown that air pollution is associated with an increased incidence of asthma, but little is known about how air pollutants affect health outside a defined buffer. The aim of this study was to better understand how air pollutants affect asthma patient visits in a metropolitan area. The study used an integrated spatial and temporal approach that included the Kriging method and the Generalized Additive Model (GAM). We analyzed daily outpatient and emergency visit data from the Taiwan Bureau of National Health Insurance and air pollution data from the Taiwan Environmental Protection Administration during 2000-2002. In general, children (aged 0-15 years) had the highest number of total asthma visits. Seasonal changes of PM10, NO2, O3 and SO2 were evident. However, SO2 showed a positive correlation with the dew point (r = 0.17, p < 0.01) and temperature (r = 0.22, p < 0.01). Among the four pollutants studied, the elevation of NO2 concentration had the highest impact on asthma outpatient visits on the day that a 10% increase of concentration caused the asthma outpatient visit rate to increase by 0.30% (95% CI: 0.16%~0.45%) in the four pollutant model. For emergency visits, the elevation of PM10 concentration, which occurred two days before the visits, had the most significant influence on this type of patient visit with an increase of 0.14% (95% CI: 0.01%~0.28%) in the four pollutants model. The impact on the emergency visit rate was non-significant two days following exposure to the other three air pollutants. This preliminary study demonstrates the feasibility of an integrated spatial and temporal approach to assess the impact of air pollution on asthma patient visits. The results of this study provide a better understanding of the correlation of air pollution with asthma patient visits and demonstrate that NO2 and PM10 might have a positive impact on outpatient and emergency settings respectively. Future research is required to validate robust spatiotemporal patterns and trends.


Prevalence of Fusobacterium necrophorum in Children Presenting with Pharyngitis.
Fusobacterium necrophorum, an obligate anaerobic bacterium, was recently reported to be an important cause of bacterial pharyngitis with a prevalence as high as that of group A Streptococcus (GAS) in adolescents and young adults. Importantly, F. necrophorum is the primary causative agent of the life-threatening Lemierre's syndrome, and screening of pharyngeal samples may be warranted for its early detection and prevention. The aim of this study was to determine the prevalences of F. necrophorum and groups A and C/G streptococci as agents of bacterial pharyngitis in children. Pharyngeal samples (n = 300) were collected from pediatric patients presenting to the emergency department with signs and symptoms of pharyngitis. Overall, 10 (3.3%), 79 (26.3%), and 4 (1.3%) patients were PCR positive for F. necrophorum, GAS, and group C/G streptococci, respectively. The prevalence of F. necrophorum was significantly higher in patients between the ages of 14 and 20 years at 13.5% than in patients aged 14 years and younger (1.9%, P < 0.001). All positive patients presented with signs and symptoms similar to GAS pharyngitis. Our data demonstrated a potential role for F. necrophorum as a pathogen of pharyngitis among young adults, but suggests that the prevalence of F. necrophorum is low in preadolescent patients.


Ketamine Use for Prolonged Field Care Reduces Supply Use.
This case describes the prolonged treatment of a 38-year-old man with a transpelvic gunshot wound requiring a diverting ostomy and cystostomy for damage control procedures with a comminuted acetabular and femoral head fracture. The team used a ketamine drip for prolonged field care over 48 hours. The benefit of using a ketamine drip included low supply requirement, excellent analgesia, and ease of administration, but side-effects included somnolence and atelectasis necessitating oxygen supplementation before evacuation.


Unmasking the Hypovolemic Shock Continuum: The Compensatory Reserve.
Hypovolemic shock exists as a spectrum, with its early stages characterized by subtle pathophysiologic tissue insults and its late stages defined by multi-system organ dysfunction. The importance of timely detection of shock is well known, as early interventions improve mortality, while delays render these same interventions ineffective. However, detection is limited by the monitors, parameters, and vital signs that are traditionally used in the intensive care unit (ICU). Many parameters change minimally during the early stages, and when they finally become abnormal, hypovolemic shock has already occurred. The compensatory reserve (CR) is a parameter that represents a new paradigm for assessing physiologic status, as it comprises the sum total of compensatory mechanisms that maintain adequate perfusion to vital organs during hypovolemia. When these mechanisms are overwhelmed, hemodynamic instability and circulatory collapse will follow. Previous studies involving CR measurements demonstrated their utility in detecting central blood volume loss before hemodynamic parameters and vital signs changed. Measurements of the CR have also been used in clinical studies involving patients with traumatic injuries or bleeding, and the results from these studies have been promising. Moreover, these measurements can be made at the bedside, and they provide a real-time assessment of hemodynamic stability. Given the need for rapid diagnostics when treating critically ill patients, CR measurements would complement parameters that are currently being used. Consequently, the purpose of this article is to introduce a conceptual framework where the CR represents a new approach to monitoring critically ill patients. Within this framework, we present evidence to support the notion that the use of the CR could potentially improve the outcomes of ICU patients by alerting intensivists to impending hypovolemic shock before its onset.


Two approaches to forecast Ebola synthetic epidemics.
We use two modelling approaches to forecast synthetic Ebola epidemics in the context of the RAPIDD Ebola Forecasting Challenge. The first approach is a standard stochastic compartmental model that aims to forecast incidence, hospitalization and deaths among both the general population and health care workers. The second is a model based on the renewal equation with latent variables that forecasts incidence in the whole population only. We describe fitting and forecasting procedures for each model and discuss their advantages and drawbacks. We did not find that one model was consistently better in forecasting than the other.


Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria.
Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are pathogenically related nonmalignant bone marrow failure disorders linked to T-cell-mediated autoimmunity; they are associated with an increased risk of secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Approximately 15% to 20% of AA patients and 2% to 6% of PNH patients go on to develop secondary MDS/AML by 10 years of follow-up. Factors determining an individual patient's risk of malignant transformation remain poorly defined. Recent studies identified nearly ubiquitous clonal hematopoiesis (CH) in AA patients. Similarly, CH with additional, non-PIGA, somatic alterations occurs in the majority of patients with PNH. Factors associated with progression to secondary MDS/AML include longer duration of disease, increased telomere attrition, presence of adverse prognostic mutations, and multiple mutations, particularly when occurring early in the disease course and at a high allelic burden. Here, we will review the prevalence and characteristics of somatic alterations in AA and PNH and will explore their prognostic significance and mechanisms of clonal selection. We will then discuss the available data on post-AA and post-PNH progression to secondary MDS/AML and provide practical guidance for approaching patients with PNH and AA who have CH.


Association between mental health status and sleep status among adolescents in Japan: a nationwide cross-sectional survey.
Previous epidemiological studies on relationships between mental health status and sleep status of adolescents have not been sufficiently representative. In the present study, using samples representative of Japanese adolescents nationwide, associations between mental health status and various sleep statuses were examined. The survey was conducted in December 2004 and January 2005 among students enrolled in randomly selected junior and senior high schools throughout Japan, using self-administered questionnaires that addressed lifestyle, sleep status, mental health status, and personal data. Of 103,650 questionnaires collected, 99,668 were analyzed. Sleep status was assessed according to sleep duration, subjective sleep assessment, bedtime, and insomnia symptoms. The Japanese version of the 12-item General Health Questionnaire was employed for assessment of mental health status. Mental health status of subjects whose sleep duration was less than 7 hours, and those who slept 9 hours or more, was poorer than that of subjects who slept for 7 hours or more but less than 9 hours. A U-shaped association was observed between mental health status and sleep duration. Furthermore, a linear association was observed between subjective sleep assessment and mental health status; the worse the subjective sleep assessment, the poorer the mental health status. Mental health status was also inversely proportional to the frequency of insomnia symptoms. The fact that sleep duration and subjective sleep assessment showed different patterns of association with mental health status indicates that these 2 sleep parameters have independent significance. Considering these associations, it is important to promote mental health care and sleep hygiene education for adolescents.


Consequences of partial and total plantar fascia release: a finite element study.
Plantar fasciotomy, a common operative procedure to relieve chronic heel pain, has been suggested to decrease foot arch stability. A systematic evaluation of the biomechanical consequences of partial or total plantar fascia release is essential to the understanding of the biomechanical rationale behind these operative procedures. A geometrical detailed three-dimensional (3-D) finite element (FE) model of the human foot and ankle, incorporating geometrical and contact nonlinearities, was constructed by 3-D reconstruction of MR images. Partial and complete plantar fascia releases were simulated to evaluate the corresponding biomechanical effects on load distribution of the bony, ligamentous, and encapsulated soft-tissue structures. Partial and total plantar fascia release may decrease arch height but did not necessarily cause total collapse of the foot arch even with additional dissection of the long plantar ligament. Operative release of the plantar fascia was compromised by increased strains of the plantar ligaments and intensified stress in the midfoot and metatarsal bones. Load redistribution among the centralized metatarsal bones and focal stress relief at the calcaneal insertion were predicted with different types of fasciotomy. The FE model suggested that plantar fascia release may provide relief of focal stress and therefore could relieve associated heel pain. However, these operative procedures may pose a risk to arch stability and clinically may produce dorsolateral midfoot pain. The initial strategy for treating plantar fasciitis should be nonoperative. If surgery is necessary, partial release of less than 40% of the fascia is recommended to minimize the effect on arch instability and maintain normal foot biomechanics.


The proximal aspect of the suspensory ligament in the horse: How precise are ultrasonographic measurements?
To evaluate intra- and interobserver variability in ultrasonographic measurements of the proximal aspect of the suspensory ligament (PSL) in the horse. A minimum difference of ≥20% is required to differentiate reliably between physiological and pathological alterations related to dimensions. Two operators examined the PSL in all 4 limbs of 14 horses twice using different techniques and different probes with and without standoff pads. Measurements were taken from the longitudinal and transverse images. Inter- and intraoperator variability was evaluated using agreement indices (AI) and the 95% limits of agreement (LOA). On the longitudinal scan the mean inter- and intraoperator AIs for dorsopalmar/-plantar thickness were both ≥0.89 and the 95% LOA were within target values for almost all intra- and interoperator comparisons. Similar mean AIs and 95% LOA were calculated for the dorsopalmar/-plantar thickness on the transverse image. For lateromedial width, cross-sectional area and circumference on the transverse scan, the mean inter- and intraoperator AIs ranged between 0.81 and 0.95 and the 95% LOA were higher than target values regardless of the imaging technique used. In general, better values for AIs and 95% LOA were achieved in the fore- compared with the hindlimb. Acceptable precision was identified within and between operators only for the dorsopalmar/-plantar thickness in longitudinal and in transverse scanning directions. For the lateromedial width, cross-sectional area and circumference, a relatively large variability was identified. This aspect has to be considered if these parameters are to be used for objective measurement of the PSL from the transverse ultrasound image.


Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies.
Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival. Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24-1.46), OR = 1.50 (95% CI 1.38-1.62), OR = 1.62 (95% CI 1.28-2.05), OR = 1.57 (95% CI 1.37-1.81), OR = 1.24 (95% CI 1.02-1.5), and OR = 1.99 (95% CI 1.67-2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95-1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88-1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals. This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675).


Body Parts Dependent Joint Regressors for Human Pose Estimation in Still Images.
In this work, we address the problem of estimating 2d human pose from still images. Articulated body pose estimation is challenging due to the large variation in body poses and appearances of the different body parts. Recent methods that rely on the pictorial structure framework have shown to be very successful in solving this task. They model the body part appearances using discriminatively trained, independent part templates and the spatial relations of the body parts using a tree model. Within such a framework, we address the problem of obtaining better part templates which are able to handle a very high variation in appearance. To this end, we introduce parts dependent body joint regressors which are random forests that operate over two layers. While the first layer acts as an independent body part classifier, the second layer takes the estimated class distributions of the first one into account and is thereby able to predict joint locations by modeling the interdependence and co-occurrence of the parts. This helps to overcome typical ambiguities of tree structures, such as self-similarities of legs and arms. In addition, we introduce a novel data set termed FashionPose that contains over 7,000 images with a challenging variation of body part appearances due to a large variation of dressing styles. In the experiments, we demonstrate that the proposed parts dependent joint regressors outperform independent classifiers or regressors. The method also performs better or similar to the state-of-the-art in terms of accuracy, while running with a couple of frames per second.


The cognitive science of technology.
Technology is central to human life but hard to define and study. This review synthesizes advances in fields from anthropology to evolutionary biology and neuroscience to propose an interdisciplinary cognitive science of technology. The foundation of this effort is an evolutionarily motivated definition of technology that highlights three key features: material production, social collaboration, and cultural reproduction. This broad scope respects the complexity of the subject but poses a challenge for theoretical unification. Addressing this challenge requires a comparative approach to reduce the diversity of real-world technological cognition to a smaller number of recurring processes and relationships. To this end, a synthetic perceptual-motor hypothesis (PMH) for the evolutionary-developmental-cultural construction of technological cognition is advanced as an initial target for investigation.


Sharps management in hospital: an audit of equipment, practice and awareness.
The safe handling and disposal of needles and other sharp instruments forms part of an overall strategy to protect staff, patients and visitors from exposure to blood-borne pathogens. As with many infection prevention and control policies, the assessment and management of the risks associated with the use of sharps is paramount, and safe systems of work and engineering controls must be in place to minimize any identified risks. The use of sharps in hospitals should be avoided where possible; when their use is essential, particular care is required in handling and disposal - if possible, use safer sharps devices. An audit of sharps management was undertaken to observe equipment, practice and awareness. The audit reported very positive results. However, some areas needed further review to improve practice. The infection control team implemented an action plan as a result of the audit and set about initiating measures for training and awareness. It is necessary to audit sharps management routinely to have an accurate assessment of current practice and prevent occupational exposure to blood-borne pathogens.


Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.
We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.


Comparison of aerobic capacity between racing standardbred horses.
A standardized treadmill test was used to compare metabolic and ventilatory measurements between 10 standardbred racehorses. The horses were divided into two groups: group A (n = 5) had mean racing speeds of 4.4 s faster than group B (n = 5) over a 1-mi. distance. Each horse was fitted with a venous catheter and connected to a valved gas-collection system. The exercise test consisted of 1-min incremental workloads ranging from 4.0 to 12.0 m/s at a treadmill incline of 3 degrees. Group A had significantly higher (P < 0.05) measurements of maximal O2 consumption (VO2max), O2 pulse, and tidal volume. Venous lactate concentration and respiratory exchange ratio measured at VO2max were also significantly higher (P < 0.05) in group A. Similar treadmill velocities were required to achieve a respiratory exchange ratio of > 1 and venous blood lactate concentration of > 4 mmol/l; however, group A was able to complete a significantly higher (P < 0.01) number of workloads before fatigue. The high aerobic and anaerobic capacity of group A horses may be a major contributor to a faster racing performance.


AtOSA1, a member of the Abc1-like family, as a new factor in cadmium and oxidative stress response.
The analysis of gene expression in Arabidopsis (Arabidopsis thaliana) using cDNA microarrays and reverse transcription-polymerase chain reaction showed that AtOSA1 (A. thaliana oxidative stress-related Abc1-like protein) transcript levels are influenced by Cd2+ treatment. The comparison of protein sequences revealed that AtOSA1 belongs to the family of Abc1 proteins. Up to now, Abc1-like proteins have been identified in prokaryotes and in the mitochondria of eukaryotes. AtOSA1 is the first member of this family to be localized in the chloroplasts. However, despite sharing homology to the mitochondrial ABC1 of Saccharomyces cerevisiae, AtOSA1 was not able to complement yeast strains deleted in the endogenous ABC1 gene, thereby suggesting different function between AtOSA1 and the yeast ABC1. The atosa1-1 and atosa1-2 T-DNA insertion mutants were more affected than wild-type plants by Cd2+ and revealed an increased sensitivity toward oxidative stress (hydrogen peroxide) and high light. The mutants exhibited higher superoxide dismutase activities and differences in the expression of genes involved in the antioxidant pathway. In addition to the conserved Abc1 region in the AtOSA1 protein sequence, putative kinase domains were found. Protein kinase assays in gelo using myelin basic protein as a kinase substrate revealed that chloroplast envelope membrane fractions from the AtOSA1 mutant lacked a 70-kD phosphorylated protein compared to the wild type. Our data suggest that the chloroplast AtOSA1 protein is a new factor playing a role in the balance of oxidative stress.


Exploring the Role of RGD-Recognizing Integrins in Cancer.
Integrins are key regulators of communication between cells and with their microenvironment. Eight members of the integrin superfamily recognize the tripeptide motif Arg-Gly-Asp (RGD) within extracelluar matrix (ECM) proteins. These integrins constitute an important subfamily and play a major role in cancer progression and metastasis via their tumor biological functions. Such transmembrane adhesion and signaling receptors are thus recognized as promising and well accessible targets for novel diagnostic and therapeutic applications for directly attacking cancer cells and their fatal microenvironment. Recently, specific small peptidic and peptidomimetic ligands as well as antibodies binding to distinct integrin subtypes have been developed and synthesized as new drug candidates for cancer treatment. Understanding the distinct functions and interplay of integrin subtypes is a prerequisite for selective intervention in integrin-mediated diseases. Integrin subtype-specific ligands labelled with radioisotopes or fluorescent molecules allows the characterization of the integrin patterns in vivo and later the medical intervention via subtype specific drugs. The coating of nanoparticles, larger proteins, or encapsulating agents by integrin ligands are being explored to guide cytotoxic reagents directly to the cancer cell surface. These ligands are currently under investigation in clinical studies for their efficacy in interference with tumor cell adhesion, migration/invasion, proliferation, signaling, and survival, opening new treatment approaches in personalized medicine.


Sport and exercise genomics: the FIMS 2019 consensus statement update.
Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders.


Sources of heterogeneity in human monocyte subsets.
Human monocytes are commonly defined and discriminated by the extent of their cell surface expression of CD14 and CD16, with associated differences in function and phenotype related to the intensity of expression of these markers. With increasing interest into the function and behaviour of monocytes, it is important to have a clear understanding of how differing strategies of analysis can affect results and how different protocols and population backgrounds can affect this highly morphogenic cell type. Using PBMCs from populations with differing ethnicities and histories of parasite exposure we have characterized monocyte phenotype based on intensity of CD14 and CD16 expression. Using the surface markers HLA-DR, CCR2 and CX3CR1, we compared monocyte phenotype between populations and further assessed changes in monocytes with freezing and thawing of PBMCs. Our results reveal that there is a progression of surface marker expression based on intensity of CD14 or CD16 expression, stressing the importance of careful gating of monocyte subtypes. Freezing and thawing of the PBMCs has no effect generally on the monocytes, although it does lead to a decrease in CD16 and CX3CR1 expression. We show that there are differences in the monocyte populations based on ethnicity and history of exposure to the common parasites Plasmodium falciparum and Schistosoma haematobium. This study highlights that blood monocytes consist of a continuous population of cells, within which the dominant phenotype may vary dependent on the background of the study population. Comparing results from monocyte studies therefore needs to be done with great care, as ethnic background of donor population, gating strategy and processing of PBMCs may all have an effect on outcome of monocyte phenotype.


Gene functional similarity search tool (GFSST).
With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. Increasing amounts of data about genes, gene products and their functions have been stored in databases. To facilitate selection of candidate genes for gene-disease research, genetic association studies, biomarker and drug target selection, and animal models of human diseases, it is essential to have search engines that can retrieve genes by their functions from proteome databases. In recent years, the development of Gene Ontology (GO) has established structured, controlled vocabularies describing gene functions, which makes it possible to develop novel tools to search genes by functional similarity. By using a statistical model to measure the functional similarity of genes based on the Gene Ontology directed acyclic graph, we developed a novel Gene Functional Similarity Search Tool (GFSST) to identify genes with related functions from annotated proteome databases. This search engine lets users design their search targets by gene functions. An implementation of GFSST which works on the UniProt (Universal Protein Resource) for the human and mouse proteomes is available at GFSST Web Server. GFSST provides functions not only for similar gene retrieval but also for gene search by one or more GO terms. This represents a powerful new approach for selecting similar genes and gene products from proteome databases according to their functions.


A 400G optical wireless integration delivery system.
We experimentally demonstrate a record 400G optical wireless integration system simultaneously delivering 2 × 112 Gb/s two-channel polarization-division-multiplexing 16-ary quadrature amplitude modulation (PDM-16QAM) signal at 37.5 GHz wireless carrier and 2 × 108 Gb/s two-channel PDM quadrature phase shift keying (PDM-QPSK) signal at 100 GHz wireless carrier, adopting two millimeter-wave (mm-wave) frequency bands, two orthogonal antenna polarizations, multiple-input multiple-output (MIMO), photonic mm-wave generation and advanced digital signal processing (DSP). In the case of no fiber transmission, the bit error ratios (BERs) for both the 112 Gb/s PDM-16QAM signal after 1.5 m wireless delivery at 37.5 GHz and the 108 Gb/s PDM-QPSK signal after 0.7 m wireless delivery at 100 GHz are below the pre-forward-error-correction (pre-FEC) threshold of 3.8 × 10(-3). To our knowledge, this is the first demonstration of a 400G optical wireless integration system in mm-wave frequency bands and also a capacity record of wireless delivery.


Future-Focused Therapeutic Strategies for Integrative Health.
For many years, the therapy field was dominated by a focus on the past. In this context, many clinicians were trained to use hypnosis as a tool to explore the past, and there is a rich literature documenting the use of hypnosis as a tool to induce age regression and the uncovering of traumatic memories. This article presents a therapeutic paradigm that focuses on the future. Hypnosis is used to induce creativity, flexibility, and openness to the future. In the context of health care, hypnosis is used to explore the best possible treatment outcome, which may be pharmacological, surgical, or a combination of both as well as other nonsurgical interventions. This article elaborates on the effective use of a therapeutic hypnosis strategy and technique focused on the future.


Inhibition of steroid sulphatase activity by tricyclic coumarin sulphamates.
The identification of the active pharmacophore required for potent inhibition of steroid sulphatase activity, i.e. an aryl-O-sulphamate structure, has led to the synthesis and testing of a large number of 1-4 ring-based inhibitors. 4-Methylcoumarin-7-O-sulphamate (COUMATE) was one of the first non-steroid based inhibitors identified. In an attempt to increase the potency of this class of inhibitor a series of tricyclic COUMATEs (665-6615 COUMATEs) have been synthesised and evaluated. Using placental microsomes as a source of oestrone sulphatase (E1-STS) the size of the third ring of the tricyclic COUMATEs was found to have a marked effect on inhibitor potency. Whereas 665- and 6615-COUMATEs had IC(50)s of 200 and 370 nM, respectively, the most potent inhibitor in vitro in this series was 6610 COUMATE with an IC(50) of 1 nM. Selected inhibitors were tested for their in vivo potency by administration of a single dose (0.1 or 1 mg/kg, p.o.) to female rats. Surprisingly, in vivo 6615 COUMATE proved to be the most active drug, inhibiting rat liver E1-STS activity by 23 and 94% when assayed 24 h after administration of the 0.1 and 1 mg/kg doses. E1-STS activity in brain tissue and white blood cells was also found to be inhibited when selected drugs were tested. These studies have identified a number of tricyclic COUMATEs with therapeutic potential.


Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules.
Most antigenic peptides presented by MHC class I molecules result from the degradation of intracellular proteins by the proteasome. In lymphoid tissues and cells exposed to IFNγ, the standard proteasome is replaced by the immunoproteasome, in which all of the standard catalytic subunits β1, β2, and β5 are replaced by their inducible counterparts β1i, β2i, and β5i, which have different cleavage specificities. The immunoproteasome thereby shapes the repertoire of antigenic peptides. The existence of additional forms of proteasomes bearing a mixed assortment of standard and inducible catalytic subunits has been suggested. Using a new set of unique subunit-specific antibodies, we have now isolated, quantified, and characterized human proteasomes that are intermediate between the standard proteasome and the immunoproteasome. They contain only one (β5i) or two (β1i and β5i) of the three inducible catalytic subunits of the immunoproteasome. These intermediate proteasomes represent between one-third and one-half of the proteasome content of human liver, colon, small intestine, and kidney. They are also present in human tumor cells and dendritic cells. We identified two tumor antigens of clinical interest that are processed exclusively either by intermediate proteasomes β5i (MAGE-A3(271-279)) or by intermediate proteasomes β1i-β5i (MAGE-A10(254-262)). The existence of these intermediate proteasomes broadens the repertoire of antigens presented to CD8 T cells and implies that the antigens presented by a given cell depend on their proteasome content.


Weight dependent modulation of motor resonance induced by weight estimation during observation of partially occluded lifting actions.
Seeing others performing an action induces the observers' motor cortex to "resonate" with the observed action. Transcranial magnetic stimulation (TMS) studies suggest that such motor resonance reflects the encoding of various motor features of the observed action, including the apparent motor effort. However, it is unclear whether such encoding requires direct observation or whether force requirements can be inferred when the moving body part is partially occluded. To address this issue, we presented participants with videos of a right hand lifting a box of three different weights and asked them to estimate its weight. During each trial we delivered one transcranial magnetic stimulation (TMS) pulse over the left primary motor cortex of the observer and recorded the motor evoked potentials (MEPs) from three muscles of the right hand (first dorsal interosseous, FDI, abductor digiti minimi, ADM, and brachioradialis, BR). Importantly, because the hand shown in the videos was hidden behind a screen, only the contractions in the actor's BR muscle under the bare skin were observable during the entire videos, while the contractions in the actor's FDI and ADM muscles were hidden during the grasp and actual lift. The amplitudes of the MEPs recorded from the BR (observable) and FDI (hidden) muscle increased with the weight of the box. These findings indicate that the modulation of motor excitability induced by action observation extends to the cortical representation of muscles with contractions that could not be observed. Thus, motor resonance appears to reflect force requirements of observed lifting actions even when the moving body part is occluded from view.


Highly sensitive compact refractive index sensor based on phase-shifted sidewall Bragg gratings in slot waveguide.
The geometrical and physical parameters of phase-shifted sidewall Bragg gratings in a silicon slot waveguide are optimized to possess performance characteristics desirable for integrated optical sensors. By tailoring the spectral response of such phase-shifted sidewall gratings, highly sensitive compact refractive index sensors detecting the resonance wavelength shift or the variation of light intensity are designed with the transfer matrix method. Both refractive index sensors have a minimum detection limit on the order of 10(-6), and a linear response and a compact structure dimension as small as 11.7 μm, offering the capabilities for sensor array and lab-on-a-chip integration. The resonance-shift sensor has a much wider detection range of 1.32 refractive index units than the intensity-measurement sensor. The performance parameters are compared with other refractive index sensors, including Mach-Zehnder interferometers, ring resonators, surface gratings, and phase-shifted gratings in silicon nanowire.


Women's efforts to prevent pregnancy: consistency of oral contraceptive use.
An understanding of determinants of inconsistent pill-taking could be useful to service providers who are trying to help women prevent unwanted pregnancy. This article explores the predictors of inconsistent use in a nationally representative sample of U.S. women aged 15-44. Data on 1,485 pill users participating in the 1995 National Survey of Family Growth are used to describe users' characteristics, and logistic regression analyses are conducted to identify factors that predict inconsistent use (defined as missing two or more pills in a three-month period) among both users of the pill only and dual method users. While 85% of pill users rely solely on the pill, 15% also use another method. Overall, 16% of users are inconsistent in their pill-taking (16% of those using the pill alone and 20% of dual method users). Among users of the pill only, Hispanic and non-Hispanic black women have a significantly increased likelihood of inconsistent use (odds ratios, 2.5 and 2.1, respectively), as do those who recently began use (2.7) and those who have had an unintended pregnancy (1.6). For dual method users, the odds are significantly elevated among women whose income is less than 250% of the federal poverty level (4.3) and among new users (4.5). Service providers may need to better address consistency of pill-taking among women who have characteristics associated with inconsistent use.


Compressible colloidal clusters from Pickering emulsions and their DNA functionalization.
Colloidal clusters were prepared by assembling azide-functionalized non-crosslinked polymer particles using fluorinated oil-in-water emulsion droplets. The particles were adsorbed onto the droplet interface, which were packed to form clusters during slow evaporation of the oil. Then, the clusters were coated by DNA using an alkyne-azide cycloaddition (SPAAC) reaction. As the particles are not crosslinked, the shape of the DNA-coated clusters can be further modified to control the compression ratio through plasticization.


Predictors and Moderators of Quality of Life Among College Students With ADHD.
Objective: The current study examines (a) whether ADHD among college students is associated with differences in perceptions of quality of life (QoL); (b) the moderating roles of comorbidity, drug use, psychopharmacological treatment, and psychosocial treatment; and (c) the total impact of these variables on QoL. Method: Participants were college students with and without ADHD (N = 372) in a longitudinal study. Results: College students with ADHD were more likely to assert negative global QoL evaluations relative to non-ADHD peers. The relationship between ADHD and QoL was not altered as a function of medication treatment, comorbid psychopathology, psychosocial treatment, or drug use. Conclusion: College students with ADHD behave similarly to other adults with ADHD in that they make lower subjective global evaluations of their QoL relative to their non-ADHD agemates. Other factors associated with ADHD and QoL do not appear to moderate this relationship.


Regulatory variant of the TPH2 gene and early life stress are associated with heightened attention to social signals of fear in infants.
Cross-species evidence suggests that genetic and experiential factors act early in development to establish individual emotional traits, but little is known about the mechanisms that emerge during this period to mediate long-term outcomes. Here, we tested the hypothesis that known genetic and environmental risk conditions may heighten infants' natural tendency to attend to threat-alerting stimuli, resulting in a cognitive bias that may contribute to emotional vulnerability. Data from two samples of 5-7-month-old infants (N = 139) were used to examine whether established candidate variations in the serotonin-system genes, i.e., TPH2 SNP rs4570625 (-703 G/T) and HTR1A SNP rs6295 (-1019 G/C), and early rearing condition (maternal stress and depressive symptoms) are associated with alterations in infants' attention to facial expressions. Infants were tested with a paradigm that assesses the ability to disengage attention from a centrally presented stimulus (a nonface control stimulus or a neutral, happy, or fearful facial expression) toward the location of a new stimulus in the visual periphery (a geometric shape). TPH2 -703 T-carrier genotype (i.e., TT homozygotes and heterozygotes), presence of maternal stress and depressive symptoms, and a combination of the T-carrier genotype and maternal depressive symptoms were associated with a relatively greater difficulty disengaging attention from fearful facial expressions. No associations were found with infants' temperamental traits. Alterations in infants' natural attentional bias toward fearful facial expressions may emerge prior to the manifestation of emotional and social behaviors and provide a sensitive marker of early emotional development.


Modelling foetal exposure to maternal smoking using hepatoblasts from pluripotent stem cells.
The liver is a dynamic organ which is both multifunctional and highly regenerative. A major role of the liver is to process both endo and xenobiotics. Cigarettes are an example of a legal and widely used drug which can cause major health problems for adults and constitute a particular risk to the foetus, if the mother smokes during pregnancy. Cigarette smoke contains a complex mixture of thousands of different xenobiotics, including nicotine and polycyclic aromatic hydrocarbons. These affect foetal development in a sex-specific manner, inducing sex-dependant molecular responses in different organs. To date, the effect of maternal smoking on the foetal liver has been studied in vitro using cell lines, primary tissue and animal models. While these models have proven to be useful, poor cell phenotype, tissue scarcity, batch-to-batch variation and species differences have led to difficulties in data extrapolation toward human development. Therefore, in this study we have employed hepatoblasts, derived from pluripotent stem cells, to model the effects of xenobiotics from cigarette smoke on human hepatocyte development. Highly pure hepatocyte populations (>90%) were produced in vitro and exposed to factors present in cigarette smoke. Analysis of ATP levels revealed that, independent of the sex, the majority of smoking derivatives tested individually did not deplete ATP levels below 50%. However, following exposure to a cocktail of smoking derivatives, ATP production fell below 50% in a sex-dependent manner. This was paralleled by a loss metabolic activity and secretory ability in both female and male hepatocytes. Interestingly, cell depletion was less pronounced in female hepatocytes, whereas caspase activation was ~twofold greater, indicating sex differences in cell death upon exposure to the smoking derivatives tested.


Activity, stability and 3-D structure of the Cu(ii) form of a chitin-active lytic polysaccharide monooxygenase from Bacillus amyloliquefaciens.
The enzymatic deconstruction of recalcitrant polysaccharide biomass is central to the conversion of these substrates for societal benefit, such as in biofuels. Traditional models for enzyme-catalysed polysaccharide degradation involved the synergistic action of endo-, exo- and processive glycoside hydrolases working in concert to hydrolyse the substrate. More recently this model has been succeeded by one featuring a newly discovered class of mononuclear copper enzymes: lytic polysaccharide monooxygenases (LPMOs; classified as Auxiliary Activity (AA) enzymes in the CAZy classification). In 2013, the structure of an LPMO from Bacillus amyloliquefaciens, BaAA10, was solved with the Cu centre photoreduced to Cu(i) in the X-ray beam. Here we present the catalytic activity of BaAA10. We show that it is a chitin-active LPMO, active on both α and β chitin, with the Cu(ii) binding with low nM KD, and the substrate greatly increasing the thermal stability of the enzyme. A spiral data collection strategy has been used to facilitate access to the previously unobservable Cu(ii) state of the active centre, revealing a coordination geometry around the copper which is distorted from axial symmetry, consistent with the previous findings from EPR spectroscopy.


Temporal changes in glutamate, glutamate transporters, basilar arteries wall thickness, and neuronal variability in an experimental rat model of subarachnoid hemorrhage.
Glutamate and glutamate transporters (GTs) (including glutamate/aspartate transporter, glutamate transporter-1, and excitatory amino acid carrier 1) have important roles in the pathogenesis of ischemic neurological injury. The changes in glutamate, GTs, and neuronal injury after subarachnoid hemorrhage (SAH) have not been widely investigated. In this study, we examined the changes in extracellular glutamate concentration, GTs, wall thickness of basilar arteries (BAs), and neuronal degeneration in experimental SAH rats. An intrathecal microdialysis probe was inserted into male Sprague Dawley rats. SAH was induced using a double-hemorrhage model. To measure glutamate concentrations, extracellular dialysates were collected for 30 minutes before, and daily for 7 days after SAH. Changes in neurological scores, body weight, and BA wall thickness were measured. The neuron degeneration in the hippocampus and the changes of GTs in the cerebral cortex and hippocampus were measured. Glutamate concentrations were significantly higher in SAH rats from day (D)1 to D7 after SAH compared with the sham rats, especially at D1. A significant body weight reduction and neurological defects were observed at D3 after SAH. The walls of BAs in SAH rats were significantly thicker compared with those of sham rats; the maximum change was observed at D7. Hippocampal neuronal degeneration was observed after SAH and the highest severity was at D7. The expression of GTs was downregulated after SAH and persisted for 7 days. SAH induced in the double-hemorrhage rat model may produce an excessive and prolonged increase of extracellular glutamate concentrations and downregulation of GTs, which are accompanied by BA wall thickness, and hippocampal neuronal degeneration.


Active Atoms and Interstitials in Two-Dimensional Colloidal Crystals.
We study experimentally and numerically the motion of a self-phoretic active particle in two-dimensional loosely packed colloidal crystals at fluid interfaces. Two scenarios emerge depending on the interactions between the active particle and the lattice: the active particle either navigates throughout the crystal as an interstitial or is part of the lattice and behaves as an active atom. Active interstitials undergo a run-and-tumble-like motion, with the passive colloids of the crystal acting as tumbling sites. Instead, active atoms exhibit an intermittent motion, stemming from the interplay between the periodic potential landscape of the passive crystal and the particle's self-propulsion. Our results constitute the first step towards the realization of non-close-packed crystalline phases with internal activity.


Lifestyle interventions to change trajectories of obesity-related cardiovascular risk from childhood onset to manifestation in adulthood: a joint scientific statement of the task force for childhood health of the European Association of Preventive Cardiology and the European Childhood Obesity Group.
There is an immediate need to optimize cardiovascular (CV) risk management and primary prevention of childhood obesity to timely and more effectively combat the health hazard and socioeconomic burden of CV disease from childhood development to adulthood manifestation. Optimizing screening programs and risk management strategies for obesity-related CV risk in childhood has high potential to change disease trajectories into adulthood. Building on a holistic view on the aetiology of childhood obesity, this document reviews current concepts in primary prevention and risk management strategies by lifestyle interventions. As an additional objective, this scientific statement addresses the high potential for reversibility of CV risk in childhood and comments on the use of modern surrogate markers beyond monitoring weight and body composition. This scientific statement also highlights the clinical importance of quantifying CV risk trajectories and discusses the remaining research gaps and challenges to better promote childhood health in a population-based approach. Finally, this document provides an overview on the lessons to be learned from the presented evidence and identifies key barriers to be targeted by researchers, clinicians, and policymakers to put into practice more effective primary prevention strategies for childhood obesity early in life to combat the burden of CV disease later in life.


Genetic analysis of Salmonella enteritidis biofilm formation: critical role of cellulose.
We report here a new screening method based on the fluorescence of colonies on calcofluor agar plates to identify transposon insertion mutants of Salmonella enteritidis that are defective in biofilm development. The results not only confirmed the requirement of genes already described for the modulation of multicellular behaviour in Salmonella typhimurium and other species, but also revealed new aspects of the biofilm formation process, such as two new genetic elements, named as bcsABZC and bcsEFG operons, required for the synthesis of an exopolysaccharide, digestible with cellulase. Non-polar mutations of bcsC and bcsE genes and complementation experiments demonstrated that both operons are responsible for cellulose biosynthesis in both S. enteritidis and S. typhimurium. Using two different growth media, ATM and LB, we showed that the biofilm produced by S. enteritidis is made of different constituents, suggesting that biofilm composition and regulation depends on environmental conditions. Bacterial adherence and invasion assays of eukaryotic cells and in vivo virulence studies of cellulose-deficient mutants indicated that, at least under our experimental conditions, the production of cellulose is not involved in the virulence of S. enteritidis. However, cellulose-deficient mutants were more sensitive to chlorine treatments, suggesting that cellulose production and biofilm formation may be an important factor for the survival of S. enteritidis on surface environments.


High yielding synthesis of 2,2'-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes.
We present an operationally simple approach to 2,2'-bipyridine macrocycles. Our method uses simple starting materials to produce these previously hard to access rotaxane precursors in remarkable yields (typically >65%) across a range of scales (0.1-5 mmol). All of the macrocycles reported are efficiently converted (>90%) to rotaxanes under AT-CuAAC conditions. With the requisite macrocycles finally available in sufficient quantities, we further demonstrate their long term utility through the first gram-scale synthesis of an AT-CuAAC [2]rotaxane and extend this powerful methodology to produce novel Sauvage-type molecular shuttles.


Intraoperative and external beam radiotherapy in advanced resectable gastric cancer: technical description and preliminary results.
Twenty-two patients with resectable gastric cancer treated with intraoperative radiotherapy and external beam irradiation, in a Phase I-II oriented study, were analyzed. Tumor Stages were III & IV in 18 cases (82%). Tumor histology was described as diffuse undifferentiated type in 14 cases (63%). Following surgical resection of the primary tumor, IORT 15 Gy was delivered in the celiac axis area, using high energy electron beams ranging from 9 to 20 MeV. External beam irradiation fields covered the draining nodal areas of the upper abdomen and the gastric bed. There were no postoperative deaths. Reversible postoperative complications were recorded in 14 patients (63%). Long term complications observed were vertebral collapse and liver hemangiomas. First sites of recurrence have been: hepatic hilum (three cases), peritoneum combined with central axis nodes (two cases), liver metastasis (one case), and lung metastasis (one case). Survival data shows a follow-up period ranging from 1+ to 33+ months, with a median survival time for the entire group of 13+ months. At the time of this report, 16 patients (72%) are still alive and six have died (four from progressive malignant disease and two from intercurrent disease). From this preliminary data, it can be concluded that a combined approach with surgical resection, intraoperative radiotherapy, and external beam irradiation is feasible in advanced gastric carcinoma, and is not limited by toxicity or any complications observed. Despite this intense loco-regional therapeutic approach, the upper abdominal failure rate has been demonstrated in 22% of the cases.


Estimating least-developed countries' vulnerability to climate-related extreme events over the next 50 years.
When will least developed countries be most vulnerable to climate change, given the influence of projected socio-economic development? The question is important, not least because current levels of international assistance to support adaptation lag more than an order of magnitude below what analysts estimate to be needed, and scaling up support could take many years. In this paper, we examine this question using an empirically derived model of human losses to climate-related extreme events, as an indicator of vulnerability and the need for adaptation assistance. We develop a set of 50-year scenarios for these losses in one country, Mozambique, using high-resolution climate projections, and then extend the results to a sample of 23 least-developed countries. Our approach takes into account both potential changes in countries' exposure to climatic extreme events, and socio-economic development trends that influence countries' own adaptive capacities. Our results suggest that the effects of socio-economic development trends may begin to offset rising climate exposure in the second quarter of the century, and that it is in the period between now and then that vulnerability will rise most quickly. This implies an urgency to the need for international assistance to finance adaptation.


Self-compression of millijoule pulses to 7.8 fs duration in a white-light filament.
We demonstrate a novel technique for pulse compression of few-millijoule pulses with shorter than 10 fs duration. Our technique relies on spectral broadening in a white-light filament generated in a noble gas. In this filament we observe self-compression of 45 fs pulses down to below 8 fs duration without the need for any additional dispersion compensation. Using input pulses of 5 mJ, we generate compressed pulses with up to 3.8 mJ pulse energy. Therefore this method is much more efficient than previously demonstrated compression schemes. The generated peak powers of more than 100 GW at a kilohertz repetition rate open up a perspective for compression of few-cycle pulses with energies well beyond the capacity of hollow-fiber compressors.


Cardiovascular risk assessment in patients with a severe mental illness: a systematic review and meta-analysis.
Cardiovascular risk (CVR) has been observed to be higher in patients with severe mental illness (SMI) than in the general population. However, some studies suggest that CVR is not equally increased in different subgroups of SMI. The purposes of this review are to summarise CVR scores of SMI patients and to determine the differences in CVR between patients with different SMIs and between SMI patients and the control-population. MEDLINE (via PubMed) was searched for literature published through August 28, 2014, followed by a snowball search in the Web of Science. Observational and experimental studies that reported CVR assessments in SMI patients using validated tools were included. The risk of bias was reported using STROBE and CONSORT criteria. Pooled continuous data were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Two reviewers independently selected studies, extracted data and assessed methodological quality. A total of 3,608 articles were identified, of which 67 full text papers were assessed for eligibility and 35 were finally included in our review, in which 12,179 psychiatric patients and 225,951 comparative patients had been assessed. The most frequent diagnoses were schizophrenia and related diagnoses (45.7%), depressive disorders (14.7%), SMI (11.4%) and bipolar disorders (8.6%). The most frequent CVR assessment tool used was the Framingham risk score. Subgroups analysis showed a higher CVR in schizophrenia than in depressive disorder or in studies that included patients with multiple psychiatric diagnoses (SMD: 0.63, 0.03, and 0.02, respectively). Six studies were included in the meta-analysis. Total overall CVR did not differ between SMI patients and controls (SMD: 0.35 [95% CI:-0.02 to 0.71], p = 0.06); high heterogeneity was observed (I (2) = 93%; p < 0.001). The summary of results from studies that assessed CVR using validated tools in SMI patients did not find sufficient data (except for limited evidence associated with schizophrenia) to permit any clear conclusions about increased CVR in this group of patients compared to the general population. The systematic review is registered in CRD42013003898 .


Electric field directed assembly of high-density microbead arrays.
We report a method for rapid, electric field directed assembly of high-density protein-conjugated microbead arrays. Photolithography is used to fabricate an array of micron to sub-micron-scale wells in an epoxy-based photoresist on a silicon wafer coated with a thin gold film, which serves as the primary electrode. A thin gasket is used to form a microfluidic chamber between the wafer and a glass coverslip coated with indium-tin oxide, which serves as the counter electrode. Streptavidin-conjugated microbeads suspended in a low conductance buffer are introduced into the chamber and directed into the wells via electrophoresis by applying a series of low voltage electrical pulses across the electrodes. Hundreds of millions of microbeads can be permanently assembled on these arrays in as little as 30 seconds and the process can be monitored in real time using epifluorescence microscopy. The binding of the microbeads to the gold film is robust and occurs through electrochemically induced gold-protein interactions, which allows excess beads to be washed away or recycled. The well and bead sizes are chosen such that only one bead can be captured in each well. Filling efficiencies greater than 99.9% have been demonstrated across wafer-scale arrays with densities as high as 69 million beads per cm(2). Potential applications for this technology include the assembly of DNA arrays for high-throughput genome sequencing and antibody arrays for proteomic studies. Following array assembly, this device may also be used to enhance the concentration-dependent processes of various assays through the accelerated transport of molecules using electric fields.


Sexual intercourse, abuse and pregnancy among adolescent women: does sexual orientation make a difference?
Although a limited amount of research has retrospectively explored the childhood and adolescent heterosexual experiences of lesbians, little is known about the prevalence of heterosexual behavior and related risk factors or about pregnancy histories among lesbian and bisexual teenagers. A secondary analysis was conducted using responses from a subsample of 3,816 students who completed the 1987 Minnesota Adolescent Health Survey. Behaviors, risk factors and pregnancy histories were compared among adolescents who identified themselves as lesbian or bisexual, as unsure of their sexual orientation and as heterosexual. Overall, bisexual or lesbian respondents were about as likely as heterosexual women ever to have had intercourse (33% and 29%, respectively), but they had a significantly higher prevalence of pregnancy (12%) and physical or sexual abuse (19-22%) than heterosexual or unsure adolescents. Among sexually experienced respondents, bisexual or lesbian and heterosexual women reported greater use of ineffective contraceptives (12-15% of those who used a method) than unsure adolescents (9%); bisexual or lesbian respondents were the most likely to have frequent intercourse (22%, compared with 15-17% of the other groups). In the sample overall, among those who were sexually experienced and among those who had ever been pregnant, bisexual or lesbian women were the most likely to have engaged in prostitution during the previous year. Providers of reproductive health care and family planning services should not assume that pregnant teenagers are heterosexual or that adolescents who say they are bisexual, lesbian or unsure of their sexual orientation are not in need of family planning counseling. Further research should explore the interactions between adolescent sexual identity development and sexual risk behaviors.


Do Bilingual Children Have an Executive Function Advantage? Results From Inhibition, Shifting, and Updating Tasks.
The purpose of this study was to examine differences in performance between monolingual and Spanish-English bilingual second graders (aged 7-9 years old) on executive function tasks assessing inhibition, shifting, and updating to contribute more evidence to the ongoing debate about a potential bilingual executive function advantage. One hundred sixty-seven monolingual English-speaking children and 80 Spanish-English bilingual children were administered 7 tasks on a touchscreen computer in the context of a pirate game. Bayesian statistics were used to determine if there were differences between the monolingual and bilingual groups. Additional analyses involving covariates of maternal level of education and nonverbal intelligence, and matching on these same variables, were also completed. Scaled-information Bayes factor scores more strongly favored the null hypothesis that there were no differences between the bilingual and monolingual groups on any of the executive function tasks. For 2 of the tasks, we found an advantage in favor of the monolingual group. If there is a bilingual advantage in school-aged children, it is not robust across circumstances. We discuss potential factors that might counteract an actual advantage, including task reliability and environmental influences.


Multi-transmitter aperture synthesis with Zernike based aberration correction.
Multi-transmitter aperture synthesis increases the effective aperture in coherent imaging by shifting the backscattered speckle field across a physical aperture or set of apertures. Through proper arrangement of the transmitter locations, it is possible to obtain speckle fields with overlapping regions, which allows fast computation of optical aberrations from wavefront differences. In this paper, we present a method where Zernike polynomials are used to model the aberrations and high-order aberrations are estimated without the need to do phase unwrapping of the difference fronts.


Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid hormone metabolism in metallothionein-deficient mouse neonates.
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain type 3 deiodinase (D3) activity in MT-I/II null and wild-type neonates. In contrast, exposure to Cd resulted in a decrease in serum T4 levels in MT-I/II null neonates. Consistently, brain D2 activity was increased in Cd-exposed MT-I/II null neonates. No significant changes in liver D1 and brain D3 activities were induced by Cd administration. Our study demonstrates that perinatal exposure to low doses of Cd or MeHg can induce changes in brain deiodinase activities in the neonates, suggesting that thyroid hormone metabolism in fetuses and neonates might be a potential target of Cd and MeHg.


A multisite-directed mutagenesis using T7 DNA polymerase: application for reconstructing a mammalian gene.
A method to introduce multiple mutations and to reconstruct genes, using a single oligodeoxyribonucleotide and DNA polymerase with high processivity, such as modified T7 DNA polymerase [Tabor and Richardson, Proc. Natl. Acad. Sci. USA 84 (1987a) 4767-4771], is described. A eukaryotic cDNA, coding for porcine growth hormone (pGH), was reconstructed in this study to delete 75 bp and to introduce a G----A transition. The deletion removes 75 bp and brings an ATG just upstream from the codon for the first amino acid in the mature protein. Moreover, the G----A substitution creates a new PvuII restriction site to facilitate further manipulation of the gene. Maximum mutation frequency with this multisite-directed mutagenesis is reached within 15 min with an efficiency approaching 50%, when using the modified T7 DNA polymerase. No multisite-directed mutants were obtained when T4 DNA polymerase or Klenow (large) fragment of DNA polymerase I were used. The described method is also applicable to simple single site-directed mutations as well as to more complex gene reconstruction strategies.