The Antimicrobial Peptide CRAMP Is Essential for Colon Homeostasis by Maintaining Microbiota Balance.
Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP-/- mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP-/- mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as Mogibacterium neglectum, Desulfovibrio piger, and Desulfomicrobium orale, were increased in feces of CRAMP-/- mice and were transferred to WT mice during cohousing. When littermates of CRAMP+/- parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP-/- and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis.


Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo.
The mammalian Polycomblike protein PHF1 was previously shown to interact with the Polycomb group (PcG) protein Ezh2, a histone methyltransferase whose activity is pivotal in sustaining gene repression during development and in adulthood. As Ezh2 is active only when part of the Polycomb Repressive Complexes (PRC2-PRC4), we examined the functional role of its interaction with PHF1. Chromatin immunoprecipitation experiments revealed that PHF1 resides along with Ezh2 at Ezh2-regulated genes such as the HoxA loci and the non-Hox MYT1 and WNT1 genes. Knockdown of PHF1 or of Ezh2 led to up-regulated HoxA gene expression. Interestingly, depletion of PHF1 did correlate with reduced occupancy of Bmi-1, a PRC1 component. As expected, knockdown of Ezh2 led to reduced levels of its catalytic products H3K27me2/H3K27me3. However, reduced levels of PHF1 also led to decreased global levels of H3K27me3. Notably, the levels of H3K27me3 decreased while those of H3K27me2 increased at the up-regulated HoxA loci tested. Consistent with this, the addition of PHF1 specifically stimulated the ability of Ezh2 to catalyze H3K27me3 but not H3K27me1/H3K27me2 in vitro. We conclude that PHF1 modulates the activity of Ezh2 in favor of the repressive H3K27me3 mark. Thus, we propose that PHF1 is a determinant in PcG-mediated gene repression.


Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex.
Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs, along with action potentials, a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. We conducted intracortical multi-electrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200-400 Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70-400 Hz), and increasing disparity with lower frequency bands (0-7, 10-40 and 50-65 Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike-based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p = 0.27[0.03]). Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. ( NCT00912041.).


Illuminance flow over anisotropic surfaces.
A theory is presented to analyze images of anisotropic fine-scale surfaces. We investigate the estimates of illuminance flow by using structure tensors. For anisotropic surfaces, both the gradient-based and the Hessian-based tensors will yield deviations from the true illumination orientation. Our theory predicts this deviation. To show the use of this theory, an algorithm is derived that uses both tensors simultaneously to compensate for small amounts of anisotropy. Experimental results with rendered surfaces are shown to conform well to our theory.


Biochemical evaluation of the protective effect of Aegle marmelos (L.), Corr. leaf extract on tissue antioxidant defense system and histological changes of pancreatic beta-cells in streptozotocin-induced diabetic rats.
Oxidative stress is produced under diabetic conditions and is likely involved in the progression of pancreatic damage found in diabetes. This study was undertaken to evaluate the protective effect of Aegle marmelos leaf extract, a medicinal plant, on the tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Ethanol extract of A. marmelos was administered orally for 30 days (150 mg/kg body weight/day) to diabetic rats. Activity of the three primary scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), levels of glutathione, and lipid peroxidation were estimated in plasma and pancreas of diabetic rats and compared to the reference drug, glibenclamide (600 microg/kg body weight/day). A significant increase in the levels of plasma glucose, vitamin E, ceruloplasmin, lipid peroxides, and a concomitant decrease in the levels of vitamin C and reduced glutathione were observed in diabetic rats. The activities of antioxidant enzymes were altered in diabetic rats. These alterations were reverted back to near normal levels after treatment with A. marmelos and glibenclamide. Histopathological studies also revealed the protective effect of A. marmelos on pancreatic beta-cells. The present study indicates that extract of A. marmelos modulates the activity of enzymic and nonenzymic antioxidants and enhances the defense against reactive oxygen species-generated damage in diabetic rats.


Osimertinib in the treatment of leptomeningeal disease in T790M-negative, epidermal growth factor receptor-mutated non-small cell lung cancer: a case report.
Leptomeningeal carcinomatosis (LMC) is a terminal event in advanced cancer, its incidence in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is increasing due to recent advances in systemic therapy and prolongation of survival. Osimertinib is a third generation EGFR-tyrosine kinase inhibitor (TKI) with preclinical and early clinical studies showing activity against LMC resistant to previous TKI treatments and acquired T790M mutation. We report a case of osimertinib in the treatment of LMC in a T790M-negative, EGFR-mutated NSCLC with significant clinical benefit and no toxicity. Osimertinib is a potentially effective treatment for LMC associated with EGFR-mutated NSCLC regardless of T790M status and a well-tolerated treatment for poor performance status patients.


Contact-free unconstraint respiratory measurements with load cells under the bed in awake healthy volunteers: breath-by-breath comparison with pneumotachography.
Rate of respiration is a fundamental vital sign. Accuracy and precision of respiratory rate measurements with contact-free load cell sensors under the bed legs were assessed by breath-by-breath comparison with the pneumotachography technique during two different dynamic breathing tasks in 16 awake human adults resting on the bed. The subject voluntarily increased and decreased the respiratory rate between 4 and 16 breaths/min (n = 8) and 10 and 40 breaths/min (n = 8) at every 2 breaths in 6 different lying postures such as supine, left lateral, right lateral, and 30, 45, and 60° sitting postures. Reciprocal phase changes of the upper and lower load cell signals accorded with the respiratory phases indicating respiratory-related shifts of the centroid along the long axis of the bed. Bland-Altman analyses revealed 0.66 and 1.59 breaths/min standard deviation differences between the techniques (limits of agreement: -1.22 to 1.36 and -2.96 to 3.30) and 0.07 and 0.17 breaths/min fixed bias differences (accuracy) (confidence interval: 0.04 to 0.10 and 0.12 to 0.22) for the mean respiratory rates of 10.5 ± 3.7 and 24.6 ± 8.9 breaths/min, respectively, regardless of the body postures on the bed. Proportional underestimation by this technique was evident for respiratory rates >40 breaths/min. Sample breath increase up to 10 breaths improved the precision from 1.59 to 0.26 breaths/min. Abnormally faster and slower respirations were accurately detected. We conclude that contact-free unconstraint respiratory rate measurements with load cells under the bed legs are accurate and may serve as a new clinical and investigational tool. NEW & NOTEWORTHY Four load cells placed under the bed legs successfully captured a centroid shift during respiration in human subjects lying on a bed. Breath-by-breath comparison of the breaths covering a wide respiratory rate range by pneumotachography confirmed reliability of the contact-free unconstraint respiratory rate measurements by small standard deviations and biases regardless of body postures. Abnormally faster and slower respirations were accurately detected. This technique should be an asset as a new clinical and investigational tool.


No-fault cerebral palsy insurance: an alternative to the obstetrical malpractice lottery.
Sixty percent of malpractice premiums paid by obstetricians go to cover suits for alleged birth-related cerebral palsy (CP). Yet substantially less than half of that money goes to CP victims, and less than 10 percent of children with CP receive any compensation at all from tort suits. This paper proposes a system that would compensate all children born with CP for most handicap-related expenses, in exchange for which the children would be foreclosed from bringing suits alleging birth-related malpractice. Malpractice would be policed by a state board, which would investigate all CP cases. This proposal would be more equitable than current systems. It would also be less expensive, since it would avoid costly litigation and decrease the cost of obstetrical malpractice insurance.


Medical characteristics of patients with macular telangiectasia type 2 (MacTel Type 2) MacTel project report no. 3.
To determine whether the prevalences of various systemic conditions in participants of the MacTel Project Natural History Observation (NHO) Study differ from the corresponding prevalences in the general population. This report compares the prevalence of systemic disease in participants of the NHO Study with age- and sex-matched controls from three population-based studies from the US, the Netherlands and Australia. Bootstrap simulations were used to evaluate the impact and reliability of the computed statistics. We identified a number of systemic conditions that appear to be more prevalent in cases with macular telangiectasia (MacTel) Type 2 than in the general population that were matched for age and sex with the MacTel cases. Patients with MacTel Type 2 had significantly increased prevalence of diabetes mellitus, higher prevalence of obesity, hypertension and history of cardiovascular disease, compared to their same-aged peers in generally older communities. Systemic disease associated with MacTel Type 2 may help to improve understanding of possible causes of MacTel Type 2. It is hoped that future studies will help to improve our understanding of the pathogenesis of the condition and lead to potential treatments for this ocular disease.


Doping induced structural changes in colloidal semiconductor nanowires.
Undoped and Mn(2+)-doped CdSe nanowires (NWs) grown by a solution-liquid-solid (SLS) method using Bi nanocatalysts have been studied by X-ray powder diffraction measurements. Except for heavily doped nanowires no measurable changes in nanowire lattice parameters were observed. The lattice parameter of heavily doped nanowires shrinks by about 0.5% compared with the undoped ones, which corresponds to a doping concentration of 1.6%. For the other samples no change in lattice parameter is measured referring to a doping level much below 1%. Real structural parameters of nanowires were found to vary as a function of doping level, such as the zinc blende to wurtzite ratio, the static Debye-Waller factor, axial strain, and the number of stacking faults. Compared with the undoped nanowires the overall perfection is slightly improved for low doping but deteriorates drastically for higher doping. Our results highlight the importance of controlling the dopant concentration during the preparation of doped nanostructures.


Late subannular aortic root rupture following transcatheter aortic valve implantation presenting as ST elevation myocardial infarction.
Transcatheter aortic valve implantation (TAVI) has transformed the treatment of severe aortic stenosis. Here, we present a case of late aortic root rupture presenting as ST-elevation myocardial infarction five weeks following successful TAVI. Aortic root rupture is a rare complication of TAVI, which occurs in ∼1% of procedures and usually arises during or soon after the procedure and is associated with high mortality (∼50%). Early recognition of late-presenting complications related to TAVI, including aortic root rupture, is essential for specialists and nonspecialists. © 2016 Wiley Periodicals, Inc.


Bone changes around hydroxyapatite and titanium implants after abutment placement in rabbits-observations using histological and three-dimensional examinations.
We have previously developed a computer-aided system for examination of the three-dimensional bone structure around implants and observed the bone changes in the healing period after implant placement. This paper describes the bone changes around hydroxyapatite (HA) and titanium (Ti) implants after abutment placement using histological and three-dimensional examinations. Twenty-four HA and Ti implants were embedded in the tibias of adult male New Zealand white rabbits. After 8 weeks, the abutment had passed through periosteum and was placed under the skin. Rabbits were sacrificed 4 and 8 weeks following abutment placement. In conclusion, histological examination showed that, at 4 weeks after abutment placement, bone resorption around the implant neck was seen in both HA and Ti implants, and at 8 weeks, excessive bone formation was seen around the implant neck. Three-dimensional bone examination showed that abutment placement may affect bone formation and cause additional bone hypertrophy in the bone marrow area.


Isolation, purification and partial characterization of plantaricin 423, a bacteriocin produced by Lactobacillus plantarum.
Lactobacillus plantarum 423, isolated from sorghum beer, produces a bacteriocin (plantaricin 423) which is inhibitory to several food spoilage bacteria and food-borne pathogens, including Bacillus cereus, Clostridium sporogenes, Enterococcus faecalis, Listeria spp. and Staphylococcus spp. Plantaricin 423 is resistant to treatment at 80 degrees C, but loses 50% of its activity after 60 min at 100 degrees C and 75% of its activity after autoclaving (121 degrees C, 15 min). Plantaricin 423 remains active after incubation at pH 1-10 and is inactivated when treated with pepsin, papain, alpha-chymotrypsin, trypsin and Proteinase K. Plantaricin 423 was partially purified and its size estimated at 3.5 kDa, as determined by tricine-SDS-PAGE. The mechanism of activity of plantaricin 423 is weakly bactericidal, as determined against Oenococcus oeni (previously Leuconostoc oenos). High DNA homology was obtained between the plasmid DNA of strain 423 and the pediocin PA-1 operon of Pediococcus acidilactici PAC 1.0, suggesting that plantaricin 423 is plasmid-encoded and related to the pediocin gene cluster.


A Smartphone App for Families With Preschool-Aged Children in a Public Nutrition Program: Prototype Development and Beta-Testing.
The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in the United States provides free supplemental food and nutrition education to low-income mothers and children under age 5 years. Childhood obesity prevalence is higher among preschool children in the WIC program compared to other children, and WIC improves dietary quality among low-income children. The Children Eating Well (CHEW) smartphone app was developed in English and Spanish for WIC-participating families with preschool-aged children as a home-based intervention to reinforce WIC nutrition education and help prevent childhood obesity. This paper describes the development and beta-testing of the CHEW smartphone app. The objective of beta-testing was to test the CHEW app prototype with target users, focusing on usage, usability, and perceived barriers and benefits of the app. The goals of the CHEW app were to make the WIC shopping experience easier, maximize WIC benefit redemption, and improve parent snack feeding practices. The CHEW app prototype consisted of WIC Shopping Tools, including a barcode scanner and calculator tools for the cash value voucher for purchasing fruits and vegetables, and nutrition education focused on healthy snacks and beverages, including a Yummy Snack Gallery and Healthy Snacking Tips. Mothers of 63 black and Hispanic WIC-participating children ages 2 to 4 years tested the CHEW app prototype for 3 months and completed follow-up interviews. Study participants testing the app for 3 months used the app on average once a week for approximately 4 and a half minutes per session, although substantial variation was observed. Usage of specific features averaged at 1 to 2 times per month for shopping-related activities and 2 to 4 times per month for the snack gallery. Mothers classified as users rated the app's WIC Shopping Tools relatively high on usability and benefits, although variation in scores and qualitative feedback highlighted several barriers that need to be addressed. The Yummy Snack Gallery and Healthy Snacking Tips scored higher on usability than benefits, suggesting that the nutrition education components may have been appealing but too limited in scope and exposure. Qualitative feedback from mothers classified as non-users pointed to several important barriers that could preclude some WIC participants from using the app at all. The prototype study successfully demonstrated the feasibility of using the CHEW app prototype with mothers of WIC-enrolled black and Hispanic preschool-aged children, with moderate levels of app usage and moderate to high usability and benefits. Future versions with enhanced shopping tools and expanded nutrition content should be implemented in WIC clinics to evaluate adoption and behavioral outcomes. This study adds to the growing body of research focused on the application of technology-based interventions in the WIC program to promote program retention and childhood obesity prevention.


Lubricin immunohistochemical expression in human temporomandibular joint disc with internal derangement.
Lubricin is a chondroprotective, mucinous glycoprotein which contribute to joint lubrication, especially to boundary lubrication and maintains joint integrity. The present investigation aimed to study the immunolocalization of lubricin in TMJ discs from patients affected by anterior disc displacement with reduction (ADDwR) ADDwoR. Eighteen TMJ displaced disc affected by ADDwoR were processed immunohistochemically, with a polyclonal anti-lubricin antibody, used at 1:50 working dilution. The percentage of lubricin immunopositive cells (extent score = ES) and the extent of lubricin staining of the disc extracellular matrix (ECM), were evaluated. Each sample was scored for histopathological changes. Percentage of immunostained surface disc cells was the same (ES = 4) in both control and ADDwOR cells, being this data not statistically significant (P < 0.05). In pathological specimens the percentages of lubricin-stained cells was very high with an ES of 4 respect to control specimen, and this difference was statistically significant different (P > 0.05). The extracellular matrix (ECM) of discs at the disc surfaces of both pathological and normal specimens was very heavily stained (++++). Both the ES and ECM staining were not statistically correlated to the TMJ degeneration score according to the Spearman's rank correlation coefficient. According to our findings, a longstanding TMJ disc injury, affects lubricin expression in the TMJ disc tissue and not its surfaces, moreover, lubricin immunostaining is not correlated to TMJ disc histopathological changes.


Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group.
To measure the effectiveness of insulin lispro, a fast-acting insulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy. In 11 diabetes outpatient clinics in the U.K., 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basal bolus regimen. Patients used human NPH insulin at night with either premeal insulin lispro for 4 months followed by human regular insulin for another 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypoglycemic episodes during both treatments and HbA1c level. A total of 135 patients were randomized, with 68 receiving insulin lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two independent groups because of a period effect and a treatment-period interaction. Glycemic control was equally tight during treatment with human regular insulin (HbA1c, 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1,156 hypoglycemic episodes occurred during treatment with human regular insulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04). This difference was chiefly because of a reduced number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group. The use of a fast-acting insulin analog, insulin lispro, as part of a basal bolus regimen reduces nocturnal hypoglycemia in patients with type 1 diabetes who maintain tight glycemic control during intensive insulin therapy.


Long-term outcome of patients with relapsed and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue.
To review the long-term outcome of patients with recurrent and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. Cohort study. A university hospital. Forty consecutive patients with recurrent or refractory germ cell tumors treated at Indiana University between September 1986 and June 1989. Patients were treated with high-dose carboplatin (900 to 2000 mg/m2 body surface area) and etoposide (1200 mg/m2). Three patients also received ifosfamide (10 g/m2). All patients had autologous bone marrow rescue. Of the 40 study patients, 26 received two full courses of therapy. Patient charts were reviewed to determine the rate and duration of complete and partial remission and the number of long-term, disease-free survivors. The influence of cisplatin-refractory disease and the site of the primary tumor on the incidence of remission and survival were also investigated. Of the 40 study patients, 26 (65%) responded to treatment; 12 (30%) achieved a complete response, and 14 (35%) achieved a partial response. Of the 12 complete responders, 5 relapsed, and 1 died of treatment-related acute leukemia 27.5 months after treatment without evidence of germ cell cancer. Six (15%) of the original 40 patients, of whom 3 were refractory to cisplatin, remained in complete remission after at least 24 months of follow-up. Eight of 40 patients had primary mediastinal germ cell tumors with no complete remissions and a median survival of 2 months (range, 0.5 to 9.0 months). Treatment with high-dose carboplatin and etoposide in conjunction with autologous bone marrow rescue in patients with relapsed or refractory germ cell tumors is a potentially curative therapeutic option, even for heavily pretreated or cisplatin-refractory patients. Some degree of disease resistance to cisplatin can be overcome with dose escalation of platinum compounds. Patients with multiple recurrences of relapsed or refractory primary mediastinal germ cell tumors were not helped by this approach.


Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-flow ischemia.
To determine whether the effects of fatty acids on the diabetic heart during ischemia involve altered glycolytic ATP and proton production, we measured energetics and intracellular pH (pH(i)) by using (31)P NMR spectroscopy plus [2-(3)H]glucose uptake in isolated rat hearts. Hearts from 7-wk streptozotocin diabetic and control rats, perfused with buffer containing 11 mM glucose, with or without 1.2 mM palmitate or the ketone bodies, 4 mM beta-hydroxybutyrate plus 1 mM acetoacetate, were subjected to 32 min of low-flow (0.3 ml x g wet wt(-1) x min(-1)) ischemia, followed by 32 min of reperfusion. In control rat hearts, neither palmitate nor ketone bodies altered the recovery of contractile function. Diabetic rat hearts perfused with glucose alone or with ketone bodies, had functional recoveries 50% lower than those of the control hearts, but palmitate restored recovery to control levels. In a parallel group with the functional recoveries, palmitate prevented the 54% faster loss of ATP in the diabetic, glucose-perfused rat hearts during ischemia, but had no effect on the rate of ATP depletion in control hearts. Palmitate decreased total glucose uptake in control rat hearts during low-flow ischemia, from 106 +/- 17 to 52 +/- 12 micromol/g wet wt, but did not alter the total glucose uptake in the diabetic rat hearts, which was 42 +/- 5 micromol/g wet wt. Recovery of contractile function was unrelated to pH(i) during ischemia; the glucose-perfused control and palmitate-perfused diabetic hearts had end-ischemic pH(i) values that were significantly different at 6.36 +/- 0.04 and 6.60 +/- 0.02, respectively, but had similar functional recoveries, whereas the glucose-perfused diabetic hearts had significantly lower functional recoveries, but their pH(i) was 6.49 +/- 0.04. We conclude that fatty acids, but not ketone bodies, protect the diabetic heart by decreasing ATP depletion, with neither having detrimental effects on the normal rat heart during low-flow ischemia.


The future of human longevity--how important are markets and innovation?
In a hearing before the United States Senate Special Committee on Aging, a well-respected demographer warns that there is no evidence of slowing in the long-term rise in best-practice life expectancy in developed countries. The author discusses how these findings will affect the future of Social Security and argues for a larger, more focused effort with respect to longevity research by demographers, epidemiologists, and economists.


Pineal gland: influence on gonads of male rats treated with androgen 3 days after birth.
Either blinding or the injection of 1 milligram of testosterone propionate into male Sprague-Dawley rats, 3 days old, results in testes and accessory organs (seminal vesicles and coagulating glands) that are smaller than normal when the rats are 72 days old. The response to blinding is prevented by removal of the pineal gland, whereas the response to treatment with testosterone is unaffected by pinealectomy. Combination of the two treatments in 3-day- old rats causes testes to be less than one-third their normal size at 72 days of age; pinealectomy in these rats permits the reproductive organs to grow to the same size as those in the androgen-treated animals.


Effect of hypoglycemia on thermoregulatory responses.
The effects of hypoglycemia on sweating, skin blood perfusion, and shivering responses were investigated in 10 healthy male volunteers. They exercised on an underwater cycle ergometer while immersed to the neck in 28 degrees C water for 20 min at 50% of their maximal work rate. The exercise-induced elevation in esophageal temperature (T(es)) initiated the sweating response (Esw) and increased skin blood perfusion (SkBP) as measured at the forehead. In the 99-min postexercise immersion period, the values of T es relative to resting level (delta T(es)) at which Esw abated, SkBP reached preexercise values, and shivering commenced were defined as the delta T(es) thresholds for cessation of sweating, passive vasodilation, and onset of shivering, respectively. Two trials were conducted 1 wk apart. The subject was hypoglycemic in one trial and euglycemic in the other (plasma glucose was maintained at 2.8 and 5 mM, respectively) with the use of the hyperinsulinemic (insulin infusion rate = 60 mU.m-2.min-1) glucose-clamp technique. Oxygen uptake, Esw, T(es), mean skin temperature, heat flux from the skin, and SkBP were recorded at minute intervals. Although heat flux and SkBP attained significantly higher end-exercise levels during euglycemia, the responses were similar during the postexercise cooling period. Hypoglycemia did not affect the Esw response during the exercise and cooling periods. Whereas the exercise delta T(es) response was unaffected by hypoglycemia, the decrease in T(es) was greater (P < or = 0.005) during the hypoglycemic than during the euglycemic condition. Hypoglycemia did not alter the delta T(es) threshold for cessation of sweating and passive vasodilation but reduced (P < or = 0.001) the delta T(es) threshold for onset of shivering (from -0.09 +/- 0.07 degrees C in the euglycemic condition to -0.65 +/- 0.12 degrees C in the hypoglycemic condition). The present results indicate that hypoglycemia (2.8 mM) does not affect the delta T(es) threshold for cessation of thermoregulatory sweating or the threshold for passive vasodilation during recovery from exercise-induced moderate heat stress but that it decreases the core temperature threshold for shivering during cold exposure.


The role of personal goals in depressive reaction to adverse life events: a cross-sectional study.
Consistent with cognitive views of depression, we aimed to investigate the mediating role of personal goals in the relationship between stressful events and distinct patterns of depressive symptoms in a nonclinical sample. Participants identified a dysphoric episode that occurred in the previous year by reporting the severity of 12 depressive symptoms and their plausible cause. A goal taxonomy was used to determine how much the event interfered with the achievement of a series of personal goals. After controlling for age and current level of depression, the patterns of symptoms differed based on the triggering events. The relationship between sadness and affective losses was partially mediated by the personal goal of lovableness, and success was a partial mediator in the association between an event of failure and symptoms of worthlessness and anhedonia. Although the cross-sectional design of the study does not allow for conclusions on the direction of effects, findings suggest the importance of motivational factors in the development of specific patterns of depressive symptoms to adverse events. Assuming a continuum from low mood to clinical depression, treatment models could benefit from a precise identification of the specific stressors that initiate depressive behaviour and the personal meaning assigned to those events.


'Catching chlamydia': combining cash incentives and community pharmacy access for increased chlamydia screening, the view of young people.
In Australia and elsewhere, chlamydia screening rates for those aged between 16 and 30 years continue to be low. Innovative, age-appropriate approaches are necessary to increase chlamydia screening among this target group to prevent short- and long-term consequences of the infection such as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and infertility. Studies have demonstrated that offering chlamydia screening in community pharmacies may be a useful adjunct to current screening services. Approximately 90% of Australians visit a pharmacy at least once a year. Chlamydia screening and education in community pharmacies with remuneration may provide another option for opportunistic testing as part of a national chlamydia screening scheme. Compensation is an accepted practice in the field of research and has been demonstrated to improve adherence to health promotion activities. In 2011, a cross-sectional study of community pharmacy-based chlamydia screening offered in conjunction with an A$10 cash incentive to participate was conducted in the Australian Capital Territory. As part of this study young people were asked about their experience of, and views about, pharmacy-based chlamydia screening. The views of consented participants were collected using the one-page questionnaire consisting of 10 closed questions and one open-ended question. Participants completed the questionnaire when they returned their urine sample and before being given the cash incentive. Overall participants were highly satisfied with the pharmacy-based chlamydia screening service. Over 60% of questionnaire respondents felt that the payment did affect their decision to have the chlamydia test, and 23% stated that it made no difference. Young people reported that pharmacy-based screening is acceptable and convenient. Accessibility and the small cash incentive played significant roles in increasing participation.


[Painful scalp ulcers].
Temporal arteritis is a systemic vasculitis mainly affecting large and medium sized vessels, temporal artery in particular. The authors report the case of a male who presented with large painful scalp ulcers over the temporo-parietal area, ipsilateral headache, amaurosis fugax and jaw claudication. Temporal arteries were thickened, painful and pulseless. Laboratory work revealed erythrocyte sedimentation rate of 63 mm and normochromic and normocytic anaemia. On histopathology transmural acute and chronic inflammation and multiple giant cells were patent in temporal artery wall. Ophthalmologic observation revealed significant visual impairment, mainly on the right eye. Regarding temporal arthritis diagnosis, prednisolone 1 mg/Kg/day was introduced. Clinical improvement was outstanding, although visual impairment remained. This case emphasizes early diagnosis and treatment importance in the avoidance of definitive sequela.


Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE epsilon4 carriers.
To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers. A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter. We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.


Variation in the Three-Dimensional Histomorphometry of the Normal Human Optic Nerve Head With Age and Race: Lamina Cribrosa and Peripapillary Scleral Thickness and Position.
This study quantified the thickness and depth of the lamina cribrosa (LC) and peripapillary scleral thickness in high-resolution three-dimensional (3D) fluorescent reconstructions of the optic nerve head (ONH) in eyes from donors of African (AD) and European descent (ED). A total of 64 eyes (45 ED, 19 AD) from 51 normal donors were obtained within 6 hours of death and fixed at 10 mm Hg of pressure. The optic nerve head was trephined from the globe and digitally reconstructed at 1.5 × 1.5 × 1.5 μm voxel resolution with an automated episcopic fluorescence technique. The load-bearing ONH connective tissue surfaces were manually delineated in 3D using custom software. The lamina cribrosa and peripapillary sclera were significantly thinner in AD eyes adjusting for age and sex (LC was 24 ± 11 μm thinner; P = 0.0350; scleral was 56 ± 22 μm thinner; P = 0.0097). The lamina cribrosa was significantly thinner in females (23 ± 11 μm thinner; P = 0.0425). Age was not significantly associated with any morphologic parameter in the ED group. However, increasing age was associated with an increase in scleral thickness (1.3 μm/year, P = 0.0499) and an increase in LC depth (2.3 μm/year, P = 0.0035) in the AD group. The sclera was thickest in the superior and temporal regions while the LC was thinnest superiorly. Substantial sectorial and racial differences in LC and scleral morphology were observed, as well as increasing LC depth and scleral thickness with age in the AD group. Results suggest greater age-related remodeling of the load-bearing ONH connective tissues in eyes from AD individuals that could explain, in part, the greater predilection to glaucomatous injury seen in aged AD populations.


Quality of reporting of bioequivalence trials comparing generic to brand name drugs: a methodological systematic review.
Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent. To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs. PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA. Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement.


Regulation of bombesin-stimulated inositol 1,4,5-trisphosphate generation in Swiss 3T3 fibroblasts by a guanine-nucleotide-binding protein.
The stimulation of inositol phosphate generation by bombesin and GTP analogues was studied in Swiss 3T3 cells permeabilized by electroporation. Bombesin-stimulated inositol phosphate generation is potentiated by guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and inhibited by guanosine 5'-[beta-thio]diphosphate at all peptide concentrations tested, with no change in the EC50 value (concn. giving half-maximal response) for the agonist. Kinetic analysis showed that, although bombesin-stimulated [3H]InsP3 generation in [3H]inositol-labelled cells was rapid (maximal by 5-10 s), the response to GTP[S] alone displayed a distinct lag time of 20-30 s. This lag time was significantly decreased by the addition of bombesin, suggesting that in this system agonist-stimulated GTP/GDP exchange occurs. In addition, bombesin-stimulated generation of Ins(1,4,5)P3 mass at 10 s was enhanced by GTP[S] in the absence of a nucleotide response alone, a result consistent with this proposal. Pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) resulted in a dose-dependent inhibition of bombesin-, but not GTP[S]-, stimulated inositol phosphate generation. Furthermore, although PMA pretreatment did not affect the lag time for InsP3 formation in response to GTP[S] alone, the degree of synergy between bombesin and the nucleotide was severely decreased at early time points. The results therefore demonstrate that the high-affinity bombesin receptor is coupled via a G-protein to phospholipase C in a manner consistent with a general model for receptor-G-protein interactions and that this coupling is sensitive to phosphorylation by protein kinase C.


miRNA: A Diagnostic and Therapeutic Tool for Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) is fatal disease and one of the major causes of death among cancer patients. Diagnosis of PDAC during the early stages of cancer using ultrasounds and blood tests is difficult and chemotherapies alone for treating cancers are not very effective. MicroRNAs (miRNAs), small non-coding RNAs that alter the expression of genes in many processes, have been identified to play a significant role in pancreatic cancer regulation. miRNAs are classified as oncomiRs (tumor inducers) and tumor suppressor miRNAs. It has been found that miRNAs are regulated very differently in serum and cells surrounding cancer cells and within cancerous cells. miRNAs regulate cancer cell proliferation, invasion, and apoptosis by being differently up-regulated or downregulated and affecting the expression of genes involved in cancer cell signaling. Therefore, miRNAs can be used as effective diagnostic markers and drug targets for therapy. In this review, we describe the most recent studies performed for understanding molecular mechanisms and gene regulations in PDAC and their utility for diagnosis and therapy.


A Bioreactor to Apply Multimodal Physical Stimuli to Cultured Cells.
Cells residing in the cardiac niche are constantly experiencing physical stimuli, including electrical pulses and cyclic mechanical stretch. These physical signals are known to influence a variety of cell functions, including the secretion of growth factors and extracellular matrix proteins by cardiac fibroblasts, calcium handling and contractility in cardiomyocytes, or stretch-activated ion channels in muscle and non-muscle cells of the cardiovascular system. Recent progress in cardiac tissue engineering suggests that controlled physical stimulation can lead to functional improvements in multicellular cardiac tissue constructs. To study these effects, aspects of the physical environment of the myocardium have to be mimicked in vitro. Applying continuous live imaging, this protocol demonstrates how a specifically designed bioreactor system allows controlled exposure of cultured cells to cyclic stretch, rhythmic electrical stimulation, and controlled fluid perfusion, at user-defined temperatures.


How Do Methyl Groups Enhance the Triplet Chemiexcitation Yield of Dioxetane?
Chemiluminescence is the emission of light as a result of a nonadiabatic chemical reaction. The present work is concerned with understanding the yield of chemiluminescence, in particular how it dramatically increases upon methylation of 1,2-dioxetane. Both ground-state and nonadiabatic dynamics (including singlet excited states) of the decomposition reaction of various methyl-substituted dioxetanes have been simulated. Methyl-substitution leads to a significant increase in the dissociation time scale. The rotation around the O-C-C-O dihedral angle is slowed; thus, the molecular system stays longer in the "entropic trap" region. A simple kinetic model is proposed to explain how this leads to a higher chemiluminescence yield. These results have important implications for the design of efficient chemiluminescent systems in medical, environmental, and industrial applications.


Extracellular vesicles released following heat stress induce bystander effect in unstressed populations.
Cells naïve to stress can display the effects of stress, such as DNA damage and apoptosis, when they are exposed to signals from stressed cells; this phenomenon is known as the bystander effect. We previously showed that bystander effect induced by ionising radiation are mediated by extracellular vesicles (EVs). Bystander effect can also be induced by other types of stress, including heat shock, but it is unclear whether EVs are involved. Here we show that EVs released from heat shocked cells are also able to induce bystander damage in unstressed populations. Naïve cells treated with media conditioned by heat shocked cells showed higher levels of DNA damage and apoptosis than cells treated with media from control cells. Treating naïve cells with EVs derived from media conditioned by heat shocked cells also induced a bystander effect when compared to control, with DNA damage and apoptosis increasing whilst the level of cell viability was reduced. We demonstrate that treatment of naïve cells with heat shocked cell-derived EVs leads to greater invasiveness in a trans-well Matrigel assay. Finally, we show that naïve cells treated with EVs from heat-shocked cells are more likely to survive a subsequent heat shock, suggesting that these EVs mediate an adaptive response. We propose that EVs released following stress mediate an intercellular response that leads to apparent stress in neighbouring cells but also greater robustness in the face of a subsequent insult.


Can smartphones be used to bring computer-based tasks from the lab to the field? A mobile experience-sampling method study about the pace of life.
Researchers are increasingly using smartphones to collect scientific data. To date, most smartphone studies have collected questionnaire data or data from the built-in sensors. So far, few studies have analyzed whether smartphones can also be used to conduct computer-based tasks (CBTs). Using a mobile experience-sampling method study and a computer-based tapping task as examples (N = 246; twice a day for three weeks, 6,000+ measurements), we analyzed how well smartphones can be used to conduct a CBT. We assessed methodological aspects such as potential technologically induced problems, dropout, task noncompliance, and the accuracy of millisecond measurements. Overall, we found few problems: Dropout rate was low, and the time measurements were very accurate. Nevertheless, particularly at the beginning of the study, some participants did not comply with the task instructions, probably because they did not read the instructions before beginning the task. To summarize, the results suggest that smartphones can be used to transfer CBTs from the lab to the field, and that real-world variations across device manufacturers, OS types, and CPU load conditions did not substantially distort the results.


Maximizing signal-to-noise ratio in the random mutation capture assay.
The 'Random Mutation Capture' assay allows for the sensitive quantitation of DNA mutations at extremely low mutation frequencies. This method is based on PCR detection of mutations that render the mutated target sequence resistant to restriction enzyme digestion. The original protocol prescribes an end-point dilution to about 0.1 mutant DNA molecules per PCR well, such that the mutation burden can be simply calculated by counting the number of amplified PCR wells. However, the statistical aspects associated with the single molecular nature of this protocol and several other molecular approaches relying on binary (on/off) output can significantly affect the quantification accuracy, and this issue has so far been ignored. The present work proposes a design of experiment (DoE) using statistical modeling and Monte Carlo simulations to obtain a statistically optimal sampling protocol, one that minimizes the coefficient of variance in the measurement estimates. Here, the DoE prescribed a dilution factor at about 1.6 mutant molecules per well. Theoretical results and experimental validation revealed an up to 10-fold improvement in the information obtained per PCR well, i.e. the optimal protocol achieves the same coefficient of variation using one-tenth the number of wells used in the original assay. Additionally, this optimization equally applies to any method that relies on binary detection of a small number of templates.


Elevational patterns of Polylepis tree height (Rosaceae) in the high Andes of Peru: role of human impact and climatic conditions.
We studied tree height in stands of high-Andean Polylepis forests in two cordilleras near Cuzco (Peru) with respect to variations in human impact and climatic conditions, and compared air and soil temperatures between qualitatively defined dry and humid slopes. We studied 46 forest plots of 100 m(2) of five Polylepis species at 3560-4680 m. We measured diameter at breast height (dbh) and tree height in the stands (1229 trees in total), as well as air and soil temperatures in a subset of plots. The data was analyzed combining plots of given species from different sites at the same elevation (±100 m). There was no elevational decrease of mean maximum tree height across the entire data set. On humid slopes, tree height decreased continuously with elevation, whereas on dry slopes it peaked at middle elevations. With mean maximum tree heights of 9 m at 4530 m on the humid slopes and of 13 m at 4650 m on the dry slopes, we here document the tallest high-elevation forests found so far worldwide. These highest stands grow under cold mean growing season air temperatures (3.6 and 3.8°C on humid vs. dry slopes) and mean growing season soil temperatures (5.1 vs. 4.6°C). Mean annual air and soil temperature both decreased with elevation. Dry slopes had higher mean and maximum growing season air temperatures than humid slopes. Mean annual soil temperatures did not significantly differ and mean annual air temperatures only slightly differed between slopes. However, maximum air temperatures differed on average by 6.6 K between dry and humid slopes. This suggests that the differences in tree height between the two slopes are most likely due to differences in solar radiation as reflected by maximum air temperatures. Our study furthermore provides evidence that alpine Polylepis treelines grow under lower temperature conditions than global high-elevation treelines on average, suggesting that Polylepis species may have evolved special physiological adaptations to low temperatures.


Personality and leadership: a qualitative and quantitative review.
This article provides a qualitative review of the trait perspective in leadership research, followed by a meta-analysis. The authors used the five-factor model as an organizing framework and meta-analyzed 222 correlations from 73 samples. Overall, the correlations with leadership were Neuroticism = -.24, Extraversion = .31, Openness to Experience = .24, Agreeableness = .08, and Conscientiousness = .28. Results indicated that the relations of Neuroticism, Extraversion, Openness to Experience, and Conscientiousness with leadership generalized in that more than 90% of the individual correlations were greater than 0. Extraversion was the most consistent correlate of leadership across study settings and leadership criteria (leader emergence and leadership effectiveness). Overall, the five-factor model had a multiple correlation of .48 with leadership, indicating strong support for the leader trait perspective when traits are organized according to the five-factor model.


Managing the public health risk of a 'sex worker' with hepatitis B infection: legal and ethical considerations.
This paper examines the ethical issues faced by health workers managing a fictional case of a female sex worker who is hepatitis B positive with a high level of virus but is asymptomatic. According to guidelines she does not require treatment herself, but is potentially highly infectious to others. Recent legal cases in the UK show it can be criminal to pass on HIV or hepatitis B infection sexually if the risk is known and the partner has not been informed. However, there is no statute or case law showing that health workers are required to intervene to prevent such a potential 'crime', particularly when the partners are unknown, as in this case. The health workers could respond in various ways. They could do nothing, thus making further infection probable. They could advise the sex worker to use condoms and to inform her clients. They could treat the sex worker to reduce her level of infectivity, although there is no benefit to her. They could disclose the sex worker's status, although breaking confidentiality is a serious matter ethically and may be of no benefit to the unknown client group. Regulating prostitution might help; but sex workers with infection may work off licence. This paper discusses the clinical, moral and ethical issues associated with such a scenario and concludes that the most beneficial course is to target clients, through health education, to recognise the potential risks of infection from a sex worker and to take suitable precautions including immunisation against hepatitis B.


Medicine dispensing service in primary health care of SUS.
To characterize the medicine dispensing services in the primary health care network in Brazil and in its different regions, aiming to promote the access and rational use of medicines. This is a cross-sectional, quantitative study with data obtained from the Pesquisa Nacional sobre Acesso, Utilização e Uso Racional de Medicamentos (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), 2015. Observation visits were carried out in 1,175 dispensing units, and interviews were held with 1,139 professionals responsible for the dispensation of medicines in the dispensing units and 495 municipal coordinators of pharmaceutical services. More than half (53%) of the units presented a space smaller than 10 m2 for dispensing of medicines; 23.8% had bars or barriers between users and dispenser; 41.7% had computerized system; and 23.7% had counters for individual care. Among those responsible for dispensation, 87.4% said they always or repeatedly inform users how to use the medicines, and 18.1% reported developing some type of clinical activity. Isolated pharmacies presented a more developed physical and personal structure than those belonging to health units, but we found no significant differences regarding the information provided and the development of clinical activities. There are major differences in the organization models of dispensation between cities, with regional differences regarding the physical structure and professionals involved. The centralization of medicine dispensing in pharmacies separated from the health services is associated with better structural and professional conditions, as in the dispensing units of the South, Southeast, and Midwest regions. However, the development of dispensation as health service does not prevail in any pharmacy or region of the Country yet.


Assessment of temporally-related acute respiratory illness following influenza vaccination.
A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods. We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons. Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]). Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.


Duration of Diabetes and Prediabetes During Adulthood and Subclinical Atherosclerosis and Cardiac Dysfunction in Middle Age: The CARDIA Study.
To determine whether the duration of diabetes and duration of prediabetes estimated during a 25-year period in early adulthood are each independently associated with coronary artery calcified plaque (CAC) and abnormalities in left ventricular structure and function later in life. Participants were 3,628 white and black adults aged 18-30 years without diabetes or prediabetes at baseline (1985-1986) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Durations of diabetes and prediabetes were estimated based on their identification at examinations 7, 10, 15, 20, and 25 years later. CAC was identified by computed tomography at years 15, 20, and 25. Left ventricular structure and function were measured via echocardiogram at year 25. Of the 3,628 individuals, 12.7% and 53.8% developed diabetes and prediabetes, respectively; average (SD) duration was 10.7 (10.7) years and 9.5 (5.4) years. After adjustment for sociodemographic characteristics and other cardiovascular risk factors, and mutual adjustment for each other, the hazard ratio for the presence of CAC was 1.15 (95% CI 1.06, 1.25) and 1.07 (1.01, 1.13) times higher for each 5-year-longer duration of diabetes and prediabetes, respectively. Diabetes and prediabetes duration were associated with worse subclinical systolic function (longitudinal strain [Ptrend < 0.001 for both]) and early diastolic relaxation (e' [Ptrend 0.004 and 0.002, respectively]). Duration of diabetes was also associated with a higher diastolic filling pressure (E-to-e' ratio [Ptrend 0.001]). Durations of diabetes and prediabetes during adulthood are both independently associated with subclinical atherosclerosis and left ventricular systolic and diastolic dysfunction in middle age.


Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review.
To conduct a systematic review of neonatal necrotising enterocolitis (NEC) rates in high-income countries published in peer-reviewed journals. We searched MEDLINE, Embase and PubMed databases for observational studies published in peer-reviewed journals. We selected studies reporting national, regional or multicentre rates of NEC in 34 Organisation for Economic Co-operation and Development countries. Two investigators independently screened studies against predetermined criteria. For included studies, we extracted country, year of publication in peer-reviewed journal, study time period, study population inclusion and exclusion criteria, case definition, gestation or birth weight-specific NEC and mortality rates. Of the 1888 references identified, 120 full manuscripts were reviewed, 33 studies met inclusion criteria, 14 studies with the most recent data from 12 countries were included in the final analysis. We identified an almost fourfold difference, from 2% to 7%, in the rate of NEC among babies born <32 weeks' gestation and an almost fivefold difference, from 5% to 22%, among those with a birth weight <1000 g but few studies covered the entire at-risk population. The most commonly applied definition was Bell's stage ≥2, which was used in seven studies. Other definitions included Bell's stage 1-3, definitions from the Centers for Disease Control and Prevention, International Classification for Diseases and combinations of clinical and radiological signs as specified by study authors. The reasons for international variation in NEC incidence are an important area for future research. Reliable inferences require clarity in defining population coverage and consistency in the case definition applied. PROSPERO INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS REGISTRATION NUMBER: CRD42015030046.


The human homolog of the JE gene encodes a monocyte secretory protein.
The mouse fibroblast gene, JE, was one of the first platelet-derived growth factor-inducible genes to be described as such. The protein encoded by JE (mJE) is the prototype of a large family of secreted, cytokinelike glycoproteins, all of whose members are induced by a mitogenic or activation signal in monocytes macrophages, and T lymphocytes; JE is the only member to have been identified in fibroblasts. We report the identification of a human homolog for murine JE, cloned from human fibroblasts. The protein predicted by the coding sequence of human JE (hJE) is 55 amino acids shorter than mJE, and its sequence is identical to that of a recently purified monocyte chemoattractant. When expressed in COS cells, the human JE cDNA directed the secretion of N-glycosylated proteins of Mr 16,000 to 18,000 as well as proteins of Mr 15,500, 15,000, and 13,000. Antibodies raised against mJE recognized these hJE species, all of which were secreted by human fibroblasts. hJE expression was stimulated in HL60 cells during phorbol myristate acetate-induced monocytoid differentiation. However, resting human monocytes constitutively secreted hJE; treatment with gamma interferon did not enhance hJE expression in monocytes, and treatment with phorbol myristate acetate or lipopolysaccharide inhibited its expression. Thus, human JE encodes yet another member of the large family of JE-related cytokinelike proteins, in this case a novel human monocyte and fibroblast secretory protein.


Restoration of clean water supply and toilet hygiene reduces infectious diseases in post-disaster evacuation shelters: A multicenter observational study.
After a massive disaster, many residents in affected areas are forced to temporarily stay in evacuation shelters. The exact impact of the state of resource supply and infrastructure in evacuation shelters on the health status of evacuees has not been sufficiently studied. Two weeks after the 2011 Great East Japan Earthquake (GEJE), comprehensive surveillance related to the health status and hygiene level was performed for all evacuation shelters (328 shelters with 46,480 evacuees at the peak) in one of the most devastating medical zones after the tsunami hit the area (Ishinomaki City). The joint relief team regularly visited all evacuation shelters across the area to assess the situation of resource supply levels, infrastructural damage, rapid need of resources, and the health status of the evacuees. In this cross-sectional observational study, we evaluated the relationship between the resource supply levels and health status among evacuees in two time periods (days 14-19 and 20-25). Among the evaluated vital resources, clean tap water supply was among the most disrupted by the disaster, and was not fully restored in most shelters during the assessment period. The cross-sectional relationship between resource supplies and morbidity was inconsistent between the two assessment periods, reflecting the multifactorial nature of health status in evacuation shelters. The clean tap water supply level at the first assessment showed a strong negative correlation with the subsequent prevalence of respiratory or gastrointestinal infectious conditions at the second assessment. Restorations in the clean tap water supply and toilet hygiene correlated each other, and both correlated with a decrease in the prevalence of gastrointestinal infectious conditions. In conclusion, disrupted clean tap water supply and inadequate toilet hygiene after a massive disaster would jointly harm the health status of those in shelters. Prompt assessments using quick visual assessment and restorations of these key resources have validity with suppressed environmental health risks among evacuees.


Forward genetic screen of human transposase genomic rearrangements.
Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates. To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. Here, we report the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates. The discovered PSS motifs and high-throughput forward chemical genomic screening approach should prove useful for the elucidation of endogenous genome remodeling activities of PGBD5 and other domesticated human DNA transposases and recombinases.


Hybrid Antimicrobial Films Containing a Polyoxometalate-Ionic Liquid.
The increasing resistance of pathogenic microorganisms against common treatments requires innovative concepts to prevent infection and avoid long-term microbe viability on commonly used surfaces. Here, we report the preparation of a hybrid antimicrobial material based on the combination of microbiocidal polyoxometalate-ionic liquids (POM-ILs) and a biocompatible polymeric support, which enables the development of surface coatings that prevent microbial adhesion. The composite material is based on an antibacterial and antifungal room-temperature POM-IL composed of guanidinium cations (N,N,N',N'-tetramethyl-N″, N″-dioctylguanidinum) combined with lacunary Keggin-type polyoxotungstate anions, [α-SiW11O39]8-. Integration of the antimicrobial POM-IL into the biocompatible, flexible, and stable polymer poly(methyl methacrylate) (PMMA) results in processable films, which are suitable as surface coatings or packaging materials to limit the proliferation and spread of pathogenic microorganisms (e.g., on public transport and hospital surfaces, or in ready-to-eat-food packaging).


Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study.
In 1986 a prospective multicenter observation trial in patients with resected gastric cancer was initiated in Germany. An analysis of prognostic factors based on the 10-year survival data is now presented. A total of 1654 patients treated for gastric cancer between 1986 and 1989 at 19 centers in Germany and Austria were included. The resected specimen were evaluated histopathologically according to a standardized protocol. The extent of lymphadenectomy was classified after surgery based on the number of removed lymph nodes on histopathologic assessment (25 or fewer removed nodes, D1 or standard lymphadenectomy; >25 removed nodes, D2 or extended lymphadenectomy). Endpoint of the study was death. Follow-up is complete for 97% of the included patients (median follow-up of the surviving patients is 8.4 years). Prognostic factors were assessed by multivariate analysis. A complete macroscopic and microscopic tumor resection (R0 resection according to the UICC 1997) could be achieved in 1182 of the 1654 patients (71.5%). The calculated 10-year survival rate in the entire patient population was 26.3% +/- 4.7%; it was 36.1% +/- 1.6% after an R0 resection. In the total patient population there was an independent prognostic effect of the ratio between invaded and removed lymph nodes, the residual tumor (R) category, the pT category, the presence of postsurgical complications, and the presence of distant metastases. Multivariate analysis in the subgroup of patients who had a UICC R0 resection confirmed the nodal status, the pT category, and the presence of postsurgical complications as the major independent prognostic factors. The extent of lymph node dissection had a significant and independent effect on the 10-year survival rate in patients with stage II tumors. This effect was present in the subgroups with (pT2N1) and without (pT3N0) lymph node metastases on standard histopathologic assessment. The beneficial effect of extended lymph node dissection for stage II tumors persisted when patients with insufficient lymph node dissection (<15 nodes) were excluded from the analysis. There was no difference in the postsurgical morbidity and mortality rates between patients with standard and extended lymph node dissection. Lymph node ratio and lymph node status are the most important prognostic factors in patients with resected gastric cancer. In experienced centers, extended lymph node dissection does not increase the mortality or morbidity rate of resection for gastric cancer but markedly improves long-term survival in patients with stage II tumors. This effect appears to be independent of the phenomenon of stage migration.


Hematochezia and thrombocytopenia in a 3-day-old infant: Congenital adenoviral infection.
Neonatal adenovirus infection is infrequent, but in most cases the outcome of the infection is fatal. In this case report we describe the hospital course of a 3 day old newborn patient presenting with bloody stools and thrombocytopenia that remained clinically stable and had a benign course following Adenovirus 40/41 infection detected in stool. Neonatal adenovirus infection should be considered in the differential diagnosis of neonatal sepsis and pneumonia but also in patients that present with hematochezia, thrombocytopenia and/or other less specific signs and symptoms of viral illness.


Developing the intervention material to increase physical activity levels of European preschool children: the ToyBox-study.
Early childhood is an important period for adopting positive health-related behaviours. More than 95% of European preschool children attend kindergartens, making these settings ideal for the implementation of health promotion interventions. The ToyBox-intervention addressed preschool children, their parents/caregivers and teachers. The aim of the intervention was to improve four energy balance-related behaviours (i.e. healthy snacking, water consumption, physical activity and sedentary behaviour) by implementing a kindergarten-based, family-involved intervention in six European countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain). The intervention material was developed following the intervention mapping protocol, taking into account local and cultural differences among the intervention countries. The present paper focuses on the development of the physical activity component of the intervention. Parental involvement was addressed by providing parents/caregivers with two newsletters, two tip cards and a poster. Teachers received a handbook with guidance on environmental changes in the classroom, 26 physical education sessions and suggestions for fun, interactive classroom activities aiming at total class participation to increase preschoolers' physical activity levels. The ToyBox-intervention material was distributed according to a standard time frame. Teachers received their material prior to the start of the intervention and parents/caregivers received their material during the intervention when each energy balance-related behaviour was implemented.


Predicting the need for phototherapy in healthy mature neonates using transcutaneous bilirubinometry on the first postnatal day.
Since newborn infants are frequently sent home within 24-48 h after birth, the prediction of severe hyperbilirubinaemia, requiring treatment, is important. We tested the prediction of the need for phototherapy by measuring the yellow skin colour and the progression in yellow skin colour over 6 h using transcutaneous bilirubinometry (TcB), during the first 33 h of age. The first TcB reading at median 21 h (11-33 h, 5th and 95th percentiles) of age and the difference in readings over a 6-hour interval were reliable predictors of later phototherapy. An even better prediction was possible using the first TcB reading and the 6-hour difference in TcB readings.


Perinatal and early infantile symptoms in congenital disorders of glycosylation.
Congenital disorders of glycosylation (CDG) are a rapidly growing family of inborn errors. Screening for CDG in suspected cases is usually performed in the first year of life by serum transferrin isoelectric focusing or mass spectrometry. Based on the transferrin analysis patients can be biochemically diagnosed with a type 1 or type 2 transferrin pattern, and labeled as CDG-I, or CDG-II. The diagnosis of CDG is frequently delayed due to the highly variable phenotype, some cases showing single organ involvement and others mimicking syndromes, like skeletal dysplasia, cutis laxa syndrome, or congenital muscle dystrophy. The aim of our study was to evaluate perinatal abnormalities and early discriminative symptoms in 58 patients consecutively diagnosed with diverse CDG-subtypes. Neonatal findings and clinical features in the first months of life were studied in 36 children with CDG-I and 22 with CDG-II. Maternal complications were found in five, small for gestational age in nine patients. Five children had abnormal neonatal screening results for hypothyroidism. Congenital microcephaly and neonatal seizures were common in CDG-II. Inverted nipples were uncommon with 5 out of 58 children. Dysmorphic features were mostly nonspecific, except for cutis laxa. Early complications included feeding problems, cardiomyopathy, thrombosis, and bleeding. Cases presenting in the neonatal period had the highest mortality rate. Survival in CDG patients is highly dependent on early intervention therapy. We recommend low threshold screening for glycosylation disorders in infants with neurologic symptoms, even in the absence of abnormal fat distribution. Growth retardation and neonatal bleeding increase suspicion for CDG.


Endoscopic management of superficial nonampullary duodenal tumors: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
1: ESGE recommends that all duodenal adenomas should be considered for endoscopic resection as progression to invasive carcinoma is highly likely.Strong recommendation, low quality evidence. 2: ESGE recommends performance of a colonoscopy, if that has not yet been done, in cases of duodenal adenoma.Strong recommendation, low quality evidence. 3: ESGE recommends the use of the cap-assisted method when the location of the minor and/or major papilla and their relationship to a duodenal adenoma is not clearly established during forward-viewing endoscopy.Strong recommendation, moderate quality evidence. 4: ESGE recommends the routine use of a side-viewing endoscope when a laterally spreading adenoma with extension to the minor and/or major papilla is suspected.Strong recommendation, low quality evidence. 5: ESGE suggests cold snare polypectomy for small (< 6 mm in size) nonmalignant duodenal adenomas.Weak recommendation, low quality evidence. 6: ESGE recommends endoscopic mucosal resection (EMR) as the first-line endoscopic resection technique for nonmalignant large nonampullary duodenal adenomas.Strong recommendation, moderate quality evidence. 7: ESGE recommends that endoscopic submucosal dissection (ESD) for duodenal adenomas is an effective resection technique only in expert hands.Strong recommendation, low quality evidence. 8: ESGE recommends using techniques that minimize adverse events such as immediate or delayed bleeding or perforation. These may include piecemeal resection, defect closure techniques, noncontact hemostasis, and other emerging techniques, and these should be considered on a case-by-case basis.Strong recommendation, low quality evidence. 9: ESGE recommends endoscopic surveillance 3 months after the index treatment. In cases of no recurrence, a further follow-up endoscopy should be done 1 year later. Thereafter, surveillance intervals should be adapted to the lesion site, en bloc resection status, and initial histological result. Strong recommendation, low quality evidence.


Gingival and periodontal alterations associated with infection with human immunodeficiency virus.
Various changes may occur in the gingiva and/or the periodontium as an expression of existing infection with human immunodeficiency virus. Thus, periodontal disease, characterized by unusual course, progress, and resistance to treatment, may occur with increased frequency. Clinically, pseudomembranous or erythematous (atrophic) forms of candidiasis or so-called papillary hyperplasia may be caused by ubiquitous fungi. Although Candida albicans infections arise frequently on the cheek, the palate, the dorsum of the tongue, and the corner of the mouth (angular cheilitis), gingivo-periodontal manifestation is more unusual. Because of the existing immune defect, infection with or reactivation of various viruses may occur. Recurrent, progressive destructive ulcerations may be caused by herpes simplex virus 1 or 2, but apparently limited ulcerations may be an expression of a disseminated cytomegalovirus infection. Oral Kaposi's sarcoma appears initially as bluish or reddish spots; these may transform during the course of the disease into blue, occasionally lymphoma-like or lymphangioma-like, exophytic tumors.


Citizen science data indicate a reduction in beach litter in the Lofoten archipelago in the Norwegian Sea.
Marine litter is a major global challenge, even in the remote reaches of the Arctic. Monitoring temporal trends in litter loadings and composition is key to designing effective preventative and mitigative measures, and to assess their impact. Few data are available, however, by which to do this in the Arctic region. Citizen science data organised by the local waste management company in the Lofoten archipelago in the Norwegian Sea is an exception to this. We analysed volunteer cleanup data (total weight and counts of select litter types, standardised to density per 100 m) from over 200 locations from 2011 to 2018. Results indicate a general decline in beach litter in the region, and particularly in litter types related to private use, such as beverage bottles. These declines are most likely the combined result of extensive cleanup activities and a considerable reduction in local litter inputs.


A random matrix approach to credit risk.
We estimate generic statistical properties of a structural credit risk model by considering an ensemble of correlation matrices. This ensemble is set up by Random Matrix Theory. We demonstrate analytically that the presence of correlations severely limits the effect of diversification in a credit portfolio if the correlations are not identically zero. The existence of correlations alters the tails of the loss distribution considerably, even if their average is zero. Under the assumption of randomly fluctuating correlations, a lower bound for the estimation of the loss distribution is provided.


Automated and robust beam data validation of a preconfigured ring gantry linear accelerator using a 1D tank with synchronized beam delivery and couch motions.
To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions. Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers these beams while measuring with the 1D tank and data logging electrometer. The program also automatically calculates this set of beams on the measurement geometry within the treatment planning system (TPS) and extracts the corresponding calculated dosimetric data for comparison to measurement. Once completed the program then returns a comparison of the measurement to the predicted result from the TPS to the user and prints a report. In this work lateral, longitudinal, and diagonal profiles were taken for fields sizes of 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 28 × 28 cm2 at depths of 1.3, 5, 10, 20, and 30 cm. Depth dose profiles were taken for all field sizes. Using this methodology, the TPS was validated to agree with measurement. All compared points yielded a gamma value less than 1 for a 1.5%/1.5 mm criteria (100% passing rate). Off axis profiles had >98.5% of data points producing a gamma value <1 with a 1%/1 mm criteria. All depth profiles produced 100% of data points with a gamma value <1 with a 1%/1 mm criteria. All data points measured were within 1.5% or 2 mm distance to agreement. This methodology allows for an increase in automation in the beam data validation process. Leveraging the application program interface allows the user to use a single system to create the measurement files, predict the result, and then compare to actual measurement increasing efficiency and reducing the chance for user input errors.


Pesticide Exposure and Stunting among Children in Agricultural Areas.
The prevalence of growth disorders among school-aged children in Indonesia is high (30.7%). Pesticides have been massively used in Indonesian agricultural areas. To determine if exposure to pesticides is associated with stunting among children in agricultural areas. This case-control study included 160 children (48 cases and 112 controls) aged 8-12 years. Exposure to pesticides was measured based on the history of the exposure since perinatal period, infancy, and childhood of the participants. Stunting was determined as a height for age z-score (HAZ) < ‑2 SD. Other variables measured were levels of thyroid stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1), hemoglobin, zinc, albumin, nutrient adequacy level (energy and protein), and history of infection, low-birth weight (LBW), and mother's height. There were no significant difference between the cases and controls in terms of in the baseline characteristics, except for the median IGF-1 level; it was significantly (p<0.001) lower in the cases (66.73 ng/mL) than the controls (112.57 ng/mL). High level of pesticide exposure (p=0.029) and low IGF-1 levels (p<0.001) were significantly associated with stunting. After adjusting for confounding variables, these variables were found to be independent risk factors for stunting in children (aOR 3.90, 95% CI 1.15 to 13.26; and aOR 8.35, 95% CI 3.65 to 19.14, respectively). Pesticide exposure could be a risk factor for the occurrence of growth disorders in children living in agricultural areas. Necessary actions should be taken to protect children living in agricultural areas from exposure to pesticides.


Ancillary Care: From Theory to Practice in International Clinical Research.
How international research might contribute to justice in global health has not been substantively addressed by bioethics. This article describes how the provision of ancillary care can link international clinical research to the reduction of global health disparities. It identifies the ancillary care obligations supported by a theory of global justice, showing that Jennifer Ruger's health capability paradigm requires the delivery of ancillary care to trial participants for a limited subset of conditions that cause severe morbidity and mortality. Empirical research on the Shoklo Malaria Research Unit's (SMRU) vivax malaria treatment trial was then undertaken to demonstrate whether and how these obligations might be upheld in a resource-poor setting. Our findings show that fulfilment of the ancillary care obligations is feasible where there is commitment from chief investigators and funders and is strongly facilitated by SMRU's dual role as a research unit and medical non-governmental organization.


Environmental exposure to cooking oil fumes and cervical intraepithelial neoplasm.
The fumes from cooking oil, similar to cigarette smoke, contain numerous carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, nitro-polycyclic aromatic hydrocarbons, etc. In this study, we examined the association between exposure to cooking oil fumes and the risk of cervical intraepithelial neoplasm. The study population in this nested case-control study consisted of women above the age of 19 years living in Chia-Yi County, located in the southwestern Taiwan, who had received pap smear screening between October, 1999, and December, 2000 (n=32,466). The potential cases were women having lesions greater than cervical intraepithelium neoplasm II (> or =CIN2) reconfirmed by cervical biopsy (n=116). The potential controls (case: control=1:2) were age-matched (+/-2 years) and residence-matched women who had normal pap smears within 6 months of the cases. In total, 100 cases and 197 controls were completely interviewed by public health nurses about cooking methods, ventilation, and other potential risk factors. Women who cooked at home in a kitchen (n=269) without the presence of a fume extractor at least once a week between the ages of 20 and 40 had a 2.29 times higher risk [95% confidence interval (CI)=1.08-4.87] of developing cervical intraepithelial neoplasm than those who did not cook once a week in such a kitchen during the same age span, after adjusting for other potential confounders. This finding was further strengthened by the finding that women who did not use the fume extractors had a 2.47 times higher risk (95% CI=1.15-5.32) of developing cervical intraepithelial neoplasm than women who cooked in kitchens with fume extractors that were always switched on while cooking. We also found a joint protective effect of fume extractor use among women older than 40 years (n=202) if they used the extractors during both age spans of their lives, ages 20-40 and >40 years. Comparing our findings on women more than 40 years old who used fume extractors during both periods, we found a 2.05-fold greater risk (95% CI=0.86-4.86) for those who used exhaust fans during only one of the two age spans and a 3.46-fold greater risk in those who had not used an exhaust fan for either period (95% CI=1.08-11.10) (trend test, P=0.02). While exposure to cooking oil fumes may cause cervical intraepithelial neoplasm, women can be protected from this risk by always cooking in kitchens equipped with fume extractors and by keeping them on while cooking.


Improved jet noise modeling using a new time-scale.
To calculate the noise emanating from a turbulent flow using an acoustic analogy knowledge concerning the unsteady characteristics of the turbulence is required. Specifically, the form of the turbulent correlation tensor together with various time and length-scales are needed. However, if a Reynolds Averaged Navier-Stores calculation is used as the starting point then one can only obtain steady characteristics of the flow and it is necessary to model the unsteady behavior in some way. While there has been considerable attention given to the correct way to model the form of the correlation tensor less attention has been given to the underlying physics that dictate the proper choice of time-scale. In this paper the authors recognize that there are several time dependent processes occurring within a turbulent flow and propose a new way of obtaining the time-scale. Isothermal single-stream flow jets with Mach numbers 0.75 and 0.90 have been chosen for the present study. The Mani-Gliebe-Balsa-Khavaran method has been used for prediction of noise at different angles, and there is good agreement between the noise predictions and observations. Furthermore, the new time-scale has an inherent frequency dependency that arises naturally from the underlying physics, thus avoiding supplementary mathematical enhancements needed in previous modeling.


Amplitude Apodizers Encoded onto Fresnel Lenses Implemented on a Phase-Only Spatial Light Modulator.
We show that both a lens and a nonuniform amplitude transmission filter can be encoded simultaneously onto a twisted nematic liquid-crystal spatial light modulator (SLM) working in the phase-only mode. The inherent equivalent apodization that is due to the pixelated structure of the SLM is compensated for. In addition, different types of nonuniform transmission pupil such as transverse apodizing, transverse hyperresolving, and axial hyperresolving (multifocusing) filters are implemented. The excellent agreement between numerical and experimental results shows the capability of this method to encode amplitude apodizers on a phase-only SLM.


The Relationship Between Humeral Retrotorsion and Shoulder Range of Motion in Baseball Players With an Ulnar Collateral Ligament Tear.
Humeral retrotorsion has been investigated in relation to shoulder range of motion (ROM) in healthy baseball players. Currently, there is limited information on the osseous anatomy and development of ulnar collateral ligament (UCL) tears. To determine the relationship between humeral retrotorsion and shoulder ROM in baseball players with a UCL tear. Cross-sectional study; Level of evidence, 3. Fifty-four baseball players (mean age, 18.5 ± 2.0 years) with a UCL tear volunteered for this study. Participants were measured bilaterally for shoulder internal (IR) and external rotation (ER) ROM and humeral retrotorsion. Differences between sides (involved to uninvolved) were used to calculate the glenohumeral internal rotation deficit (GIRD), external rotation ROM difference (ERDiff), total rotational motion difference (TRM), and humeral retrotorsion difference (HTDiff). A multivariate regression analysis was performed with GIRD, ERDiff, and TRM regressing on HTDiff. Univariate analysis was performed to further evaluate the effect of the predictors on each outcome separately. To control for the effect of age, weight, duration of symptoms, and years of experience, the variables were included as covariates. An a priori level was set at P < .05. There was a statistically significant relationship between the GIRD, ERDiff, and TRM results compared with HTDiff (P = .003). Independent analysis revealed a statistically significant relationship between GIRD and HTDiff (P = .004) and between ERDiff and HTDiff (P = .003) but no significant relationship between TRM and HTDiff (P = .999). After adjusting for age, weight, duration of symptoms, years of experience, dominant arm, and position, a significant relationship was found between GIRD and HTDiff (P = .05) and between ERDiff and HTDiff (P = .01). No significant relationship was found between TRM and HTDiff (P = .54). Adjusted univariate regression analysis determined that HTDiff explains approximately 16% of the variance in GIRD (r2 = 0.158) and approximately 24% of the variance in ERDiff (r2 = 0.237). In baseball players with a UCL tear, approximately 16% of the variance in GIRD and 24% of the variance in ERDiff can be attributed to differences found in humeral retrotorsion between sides. This indicates that humeral retroversion contributes significantly to GIRD and increased ER ROM in baseball players. Recognition of differences in humeral retrotorsion between the dominant and nondominant upper extremities may help explain some but not all of the changes in shoulder ROM commonly seen in baseball players.


Induction of activation antigens on human natural killer cells mediated through the Fc-gamma receptor.
NK cells, defined here as lymphocytes bearing the CD16 Ag found on the NK cell Fc-gamma receptor (FcR), are known to enter a proliferative and activated state in response to stimulation with IL-2 as assessed by clonal expansion, short-term DNA synthesis, and de novo expression of lymphocyte-associated activation Ag. We have found that the FcR of NK cells acts as a signaling pathway through which IL-2-dependent activation may be greatly enhanced, allowing for more rapid induction of activation Ag and recruitment of an increased percentage of cells expressing surface markers of cellular activation. FcR-interactive agents, such as solid phase immobilized immune complexes or cross-linked CD16-specific mAb, work synergistically with rIL-2 to elicit a rapid expression of IL2R and transferrin receptors on greater than 50% of purified NK cells as early as day 3 of culture. IL-2 or FcR-interactive stimuli alone were weak or ineffective stimulators by comparison. In contrast to the induction of de novo activation Ag, DNA synthesis was elicited by IL-2 alone, but was not substantially or consistently enhanced by the subsequent addition of FcR-interactive stimuli.


A Predictive-Coding Network That Is Both Discriminative and Generative.
Predictive coding (PC) networks are a biologically interesting class of neural networks. Their layered hierarchy mimics the reciprocal connectivity pattern observed in the mammalian cortex, and they can be trained using local learning rules that approximate backpropagation (Bogacz, 2017). However, despite having feedback connections that enable information to flow down the network hierarchy, discriminative PC networks are not typically generative. Clamping the output class and running the network to equilibrium yields an input sample that usually does not resemble the training input. This letter studies this phenomenon and proposes a simple solution that promotes the generation of input samples that resemble the training inputs. Simple decay, a technique already in wide use in neural networks, pushes the PC network toward a unique minimum two-norm solution, and that unique solution provably (for linear networks) matches the training inputs. The method also vastly improves the samples generated for nonlinear networks, as we demonstrate on MNIST.


Recurrent intramedullary epidermoid cyst of conus medullaris.
Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi-disciplinary treatment approach.