Religious Background and Gambling Among Young Adults in the United States.
Despite the rapid growth of the gambling industry over the last 40 years, there have been few large-scale, nationally representative longitudinal studies of gambling among young adults. We use data from the National Longitudinal Study of Adolescent to Adult Health to investigate whether and how the gambling behavior of young adults is associated with their religious beliefs and practices during adolescence. We find that young adults who grew up as conservative Protestants, mainline Protestants, Mormons, and Jehovah's Witnesses; those were raised in a community with a higher percentage of conservative Protestants; and those who attended religious services weekly are less likely to have ever gambled. Among gamblers, young adults who attended religious services up to three times per month as adolescents are more likely to experience gambling problems than those who never attend. Notably, accounting for a young adult's propensity for risk-taking behavior does not explain the associations between religion and gambling.


Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.
This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.


Characterization of acute coagulopathy and sexual dimorphism after injury: females and coagulopathy just do not mix.
Acute traumatic coagulopathy (ATC) predicts poor outcome after injury. Females have been demonstrated to be hypercoagulable early in the posttrauma period. It remains unclear whether presence of ATC alters sex-based outcomes after injury. This study's objective was to characterize the sex dimorphism after severe injury in the presence and absence of ATC. Data were obtained from a multicenter prospective cohort study of patients with blunt trauma and hemorrhagic shock. ATC was defined as arrival international normalized ratio (INR) of greater than 1.5. Cox regression was used to determine the independent risks of mortality and multiple-organ failure associated with sex in subjects with ATC and without (non-ATC) while controlling for important confounders. The sex mortality differences were characterized over time to determine at what point after injury any differential risks diverge. Of 2,007 enrolled subjects, 1,877 had an arrival INR with 439 (23%) having ATC. There was no difference in incidence of ATC across sex (24% vs. 23%; p = 0.95). In the ATC group, no difference in Injury Severity Score, arrival INR, base deficit, temperature, or 24-hour blood requirements were found across sex. Cox hazard regression revealed that sex was not associated with mortality in non-ATC patients (hazard ratio, 0.94; 95% confidence interval, 0.6-1.5). Female sex was independently associated with mortality only in the ATC group (hazard ratio, 2.04; 95% confidence interval, 1.1-3.9; p = 0.03). These mortality risk differences across sex diverged within the first 24 hours after injury. An exaggerated sex dimorphism exists for patients with ATC, with females demonstrating a twofold higher independent risk of mortality. These differential mortality risks across sex diverge early after injury, suggesting that they may be caused by an ongoing hemorrhage. Females who present with ATC at admission have a significantly greater risk of poor outcome. Further studies are warranted to explore the mechanisms responsible for sex dimorphism in the setting of ATC. Prognostic study, level II.


Transient transcriptional events in human skeletal muscle at the outset of concentric resistance exercise training.
We sought to ascertain the time course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naive individuals and determine whether the magnitude of response was associated with exercise-induced muscle damage. Sixteen RE naive men were recruited; eight underwent two sessions of 5 × 30 maximum isokinetic knee extensions (180°/s) separated by 48 h. Muscle biopsies of the vastus lateralis, obtained from different sites, were taken at baseline and 24 h after each exercise bout. Eight individuals acted as nonexercise controls with biopsies obtained at the same time intervals. Transcriptional changes were assessed by microarray and protein levels of heat shock protein (HSP) 27 and αB-crystallin in muscle cross sections by immunohistochemistry as a proxy measure of muscle damage. In control subjects, no probe sets were significantly altered (false discovery rate < 0.05), and HSP27 and αB-crystallin protein remained unchanged throughout the study. In exercised subjects, significant intersubject variability following the initial RE bout was observed in the muscle transcriptome, with greatest changes occurring in subjects with elevated HSP27 and αB-crystallin protein. Following the second bout, the transcriptome response was more consistent, revealing a cohort of probe sets associated with immune activation, the suppression of oxidative metabolism, and ubiquitination, as differentially regulated. The results reveal that the initial transcriptional response to RE is variable in RE naive volunteers, potentially associated with muscle damage and unlikely to reflect longer term adaptations to RE training. These results highlight the importance of considering multiple time points when determining the transcriptional response to RE and associated physiological adaptation.


Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies.
To apply the new American College of Rheumatology nomenclature for neuropsychiatric systemic lupus erythematosus (NPSLE), determine the prevalence of the different neuropsychiatric (NP) syndromes, and evaluate which of these manifestations correlates with the presence of antiphospholipid antibodies (aPL). Methods. Clinical, serological, and imaging data of 323 consecutive patients with SLE were retrospectively reviewed. Neuropsychometric testing was applied by a neuropsychologist. Univariate and multivariate statistical analyses were applied to evaluate the association bewteen NP manifestations, magnetic resonance imaging (MRI) abnormalities, and aPL. In total, 185 patients (57.3%) had NP manifestations at any time during followup. Headache was the most frequent manifestation, present in 78 patients (24%). Cerebrovascular disease (CVD) was diagnosed in 47/323 patients (14.5%), with a total of 57 events. Mood disorders were found in 54 (16.7%), cognitive disorders in 35 (10.8%), and seizures in 27 patients (8.3%). Psychosis was diagnosed in 25 (7.7%), anxiety disorder in 24 (3.7%), and acute confusional state in 12 patients (3.7%). Less common manifestations were polyneuropathy, mononeuritis, myasthenia gravis, cranial neuropathy, myelopathy, chorea, demyelinating disease, and Guillain-Barré syndrome. The presence of aPL was associated with NP manifestations (p < 0.001). Multivariate analysis showed that aPL were independently associated with CVD (OR 6.17, 95% CI 2.94-12.9, p = 0.001), headache (OR 2.04, 95% CI 1.17-3.55, p = 0.01), and seizures (OR 2.89, 95% CI 1.18-7.10, p = 0.02). The presence of lupus anticoagulant (LAC) was independently associated with white matter hyperintensity lesions on MRI (OR 3.0, 95% CI 1.12-8.05, p = 0.027). The new ACR criteria for NPSLE are useful to define NP manifestations in SLE with accuracy. NP manifestations are significantly associated with aPL. CVD, headache, and seizures were independently associated with these antibodies.


Partial regression of a hydatiform mole with coexisting live fetus in a twin gestation: case report.
Pregnancies resulting in viable fetuses are extremely rare in accompanying a hydatiform mole, often due to the development of maternal complications, including preeclampsia and vaginal bleeding. The risk for gestational trophoblastic neoplasm is another concern because of the delayed evacuation of the molar tissue. In this paper, the authors present a case of complete mole hydatiform with a live co-twin fetus (CHMLF) resulting in the delivery of a healthy male infant with the partial regression of the molar tissue and the decline of serum beta human chorionic gonadotropin (P-hCG) during the pregnancy. In the management of CHMLF, each patient must be considered individually and eligible patients can be followed in the absence of serious maternal complications. Serial ultrasound examinations and close clinical and laboratory surveillance of the mother are certainly indicated.


Effect of airways sensory C fiber network degeneration on airways permeability and responsiveness.
The effect of sensory nerve C fiber network degeneration on airways permeability and responsiveness was studied in guinea pigs. Degeneration of the C fiber sensory network was produced by injecting capsaicin in solvent (total dose 50 mg/kg) into neonatal animals (n = 29) with littermate animals (n = 30) treated with solvent alone serving as controls. Sensory nerve depletion was established by comparing tracheal strips from both groups of animals in vitro. When the animals reached between 400 and 500 g body weight, airways permeability to fluorescein isothiocyanate dextran (FITC-D) and airways responsiveness to a graded dose of aerosolized histamine were measured. The data show that degeneration of the C fiber network had no effect on the airways responsiveness to histamine. They also show that degeneration of the C fiber network produced a significant (P less than or equal to .01) increase in airways reactivity [0.36 +/- 0.08 cm H2O/mL s-1 (mean +/- SEM)] following cigarette smoke exposure compared with control (0.11 +/- 0.04) or control-smoke-exposed animals (0.10 +/- 0.02). Degeneration of the C fiber network did not affect the increased permeability seen following cigarette smoke exposure (capsaicin pretreated 39.8 +/- 9.1 and control pretreated 28.4 +/- 7.9 (micrograms)(min)/mg). We conclude that degeneration of the C fiber network is associated with increased rather than decreased airways responsiveness in guinea pigs exposed to cigarette smoke.


An open label, dose response study to determine the effect of a dietary supplement on dihydrotestosterone, testosterone and estradiol levels in healthy males.
Maintaining endogenous testosterone (T) levels as men age may slow the symptoms of sarcopenia, andropause and decline in physical performance. Drugs inhibiting the enzyme 5alpha-reductase (5AR) produce increased blood levels of T and decreased levels of dihydrotestosterone (DHT). However, symptoms of gynecomastia have been reported due to the aromatase (AER) enzyme converting excess T to estradiol (ES). The carotenoid astaxanthin (AX) from Haematococcus pluvialis, Saw Palmetto berry lipid extract (SPLE) from Serenoa repens and the precise combination of these dietary supplements, Alphastat(R) (Mytosterone(trade mark)), have been reported to have inhibitory effects on both 5AR and AER in-vitro. Concomitant regulation of both enzymes in-vivo would cause DHT and ES blood levels to decrease and T levels to increase. The purpose of this clinical study was to determine if patented Alphastat(R) (Mytosterone(trade mark)) could produce these effects in a dose dependent manner. To investigate this clinically, 42 healthy males ages 37 to 70 years were divided into two groups of twenty-one and dosed with either 800 mg/day or 2000 mg/day of Alphastat(R) (Mytosterone(trade mark)) for fourteen days. Blood samples were collected on days 0, 3, 7 and 14 and assayed for T, DHT and ES. Body weight and blood pressure data were collected prior to blood collection. One-way, repeated measures analysis of variance (ANOVA-RM) was performed at a significance level of alpha = 0.05 to determine differences from baseline within each group. Two-way analysis of variance (ANOVA-2) was performed after baseline subtraction, at a significance level of alpha = 0.05 to determine differences between dose groups. Results are expressed as means +/- SEM. ANOVA-RM showed significant within group increases in serum total T and significant decreases in serum DHT from baseline in both dose groups at a significance level of alpha = 0.05. Significant decreases in serum ES are reported for the 2000 mg/day dose group and not the 800 mg/day dose group. Significant within group effects were confirmed using ANOVA-2 analyses after baseline subtraction. ANOVA-2 analyses also showed no significant difference between dose groups with regard to the increase of T or the decrease of DHT. It did show a significant dose dependant decrease in serum ES levels. Both dose groups showed significant (p = 0.05) increases in T and decreases in DHT within three days of treatment with Alphastat(R) (Mytosterone(trade mark)). Between group statistical analysis showed no significant (p = 0.05) difference, indicating the effect was not dose dependent and that 800 mg/per day is equally effective as 2000 mg/day for increasing T and lowering DHT. Blood levels of ES however, decreased significantly (p = 0.05) in the 2000 mg/day dose group but not in the 800 mg/day dose group indicating a dose dependant decrease in E levels.


Expression of CHI3L1 and CHIT1 in osteoarthritic rat cartilage model. A morphological study.
Osteoarthritis is a degenerative joint disease, which affects millions of people around the world. It occurs when the protective cartilage at the end of bones wears over time, leading to loss of flexibility of the joint, pain and stiffness. The cause of osteoarthritis is unknown, but its development is associated with different factors, such as metabolic, genetic, mechanical and inflammatory ones. In recent years the biological role of chitinases has been studied in relation to different inflammatory diseases and more in particular the elevated levels of human cartilage glycoprotein 39 (CHI3L1) and chitotriosidase (CHIT1) have been reported in a variety of diseases including chronic inflammation and degenerative disorders. The aim of this study was to investigate, by immunohistochemistry, the distribution of CHI3L1 and CHIT1 in osteoarthritic and normal rat articular cartilage, to discover their potential role in the development of this disease. The hypothesis was that the expression of chitinases could increase in OA disease. Immunohistochemical analysis showed that CHI3L1 and CHIT1 staining was very strong in osteoarthritic cartilage, especially in the superficial areas of the cartilage most exposed to mechanical load, while it was weak or absent in normal cartilage. These findings suggest that these two chitinases could be functionally associated with the development of osteoarthritis and could be used as markers, so in the future they could have a role in the daily clinical practice to stage the severity of the disease. However, the longer-term in vivo and in vitro studies are needed to understand the exact mechanism of these molecules, their receptors and activities on cartilage tissue.


Evaluation of ELISA coupled with Western blot as a surveillance tool for Trichinella infection in wild boar (Sus scrofa).
Trichinella surveillance in wildlife relies on muscle digestion of large samples which are logistically difficult to store and transport in remote and tropical regions as well as labour-intensive to process. Serological methods such as enzyme-linked immunosorbent assays (ELISAs) offer rapid, cost-effective alternatives for surveillance but should be paired with additional tests because of the high false-positive rates encountered in wildlife. We investigated the utility of ELISAs coupled with Western blot (WB) in providing evidence of Trichinella exposure or infection in wild boar. Serum samples were collected from 673 wild boar from a high- and low-risk region for Trichinella introduction within mainland Australia, which is considered Trichinella-free. Sera were examined using both an 'in-house' and a commercially available indirect-ELISA that used excretory-secretory (E/S) antigens. Cut-off values for positive results were determined using sera from the low-risk population. All wild boar from the high-risk region (352) and 139/321 (43.3%) of the wild boar from the low-risk region were tested by artificial digestion. Testing by Western blot using E/S antigens, and a Trichinella-specific real-time PCR was also carried out on all ELISA-positive samples. The two ELISAs correctly classified all positive controls as well as one naturally infected wild boar from Gabba Island in the Torres Strait. In both the high- and low-risk populations, the ELISA results showed substantial agreement (k-value=0.66) that increased to very good (k-value=0.82) when WB-positive only samples were compared. The results of testing sera collected from the Australian mainland showed the Trichinella seroprevalence was 3.5% (95% C.I. 0.0-8.0) and 2.3% (95% C.I. 0.0-5.6) using the in-house and commercial ELISA coupled with WB respectively. These estimates were significantly higher (P<0.05) than the artificial digestion estimate of 0.0% (95% C.I. 0.0-1.1). Real-time PCR testing of muscle from seropositive animals did not detect Trichinella DNA in any mainland animals, but did reveal the presence of a second larvae-positive wild boar on Gabba Island, supporting its utility as an alternative, highly sensitive method in muscle examination. The serology results suggest Australian wildlife may have been exposed to Trichinella parasites. However, because of the possibility of non-specific reactions with other parasitic infections, more work using well-defined cohorts of positive and negative samples is required. Even if the specificity of the ELISAs is proven to be low, their ability to correctly classify the small number of true positive sera in this study indicates utility in screening wild boar populations for reactive sera which can be followed up with additional testing.


Quantitative and reproducible murine model of excisional wound healing.
The goal of animal wound healing models is to replicate human physiology and predict therapeutic outcomes. There is currently no model of wound healing in rodents that closely parallels human wound healing. Rodents are attractive candidates for wound healing studies because of their availability, low cost, and ease of handling. However, rodent models have been criticized because the major mechanism of wound closure is contraction, whereas in humans reepithelialization and granulation tissue formation are the major mechanisms involved. This article describes a novel model of wound healing in mice utilizing wound splinting that is accurate, reproducible, minimizes wound contraction, and allows wound healing to occur through the processes of granulation and reepithelialization. Our results show that splinted wounds have an increased amount of granulation tissue deposition as compared to controls, but the rate of reepithelialization is not affected. Thus, this model eliminates wound contraction and allows rodents' wounds to heal by epithelialization and granulation tissue formation. Given these analogies to human wound healing, we believe that this technique is a useful model for the study of wound healing mechanisms and for the evaluation of new therapeutic modalities.


Maternal MTHFR polymorphisms and risk of spontaneous abortion.
To asses the association between intake of folate and B vitamins and the incidence of spontaneous abortion (SA) according to the maternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (677 C>T and 1298 A>C). We conducted a nested case-control study within a perinatal cohort of women recruited in the state of Morelos, Mexico. Twenty-three women with SA were compared to 74 women whose pregnancy survived beyond week 20th. Intake of folate and B vitamins respectively, was estimated using a validated food frequency questionnaire. Maternal MTHFR polymorphisms were determined by PCR-RFLP and serum homocysteine levels by HPLC. Carriers of MTHFR 677TT and 1298AC genotypes respectively showed an increased risk of SA (OR 677TT vs. CC/CT=5.0; 95% CI: 1.2, 20.9 and OR 1298 AC vs. AA=5.5; 95% CI: 1.1, 26.6). Our results support the role of MTHFR polymorphisms as a risk factor for SA, regardless of dietary intake of B vitamins.


A prospective, double-blind, randomized clinical trial comparing subacromial injection of betamethasone and xylocaine to xylocaine alone in chronic rotator cuff tendinosis.
Rotator cuff tendinosis is a common problem with significant health and economic effects. Nonoperative management includes the widespread use of subacromial steroid injections despite the lack of evidence of its efficacy. A subacromial injection of betamethasone will be more effective than xylocaine alone in improving the quality of life, impingement sign, and range of motion in patients who have chronic rotator cuff tendinosis or partial rotator cuff tears. Randomized controlled clinical trial; Level of evidence, 1. Patients with rotator cuff tendinosis or partial cuff tear with symptoms longer than 6 months, with failure of 6 weeks of physical therapy and 2 weeks of nonsteroidal anti-inflammatory drugs, who were older than 30 years of age, and who showed >50% improvement with the Neer impingement test were stratified for Workplace Safety and Insurance Board status and previous injection. Outcome measures--the Western Ontario Rotator Cuff Index; American Shoulder and Elbow Surgeons standardized form; Disabilities of the Arm, Shoulder and Hand; active forward elevation; active internal rotation; active external rotation; and the Neer impingement sign--were assessed at 2, 6, 12, and 24 weeks after injection. The injection into the subacromial space contained either 5 mL of 2% xylocaine alone or 4 mL of 2% xylocaine and 1 mL (6 mg) of betamethasone in an opaque syringe. In 58 patients (betamethasone group, n = 30; xylocaine group, n = 28), the authors found no statistically significant difference between the 2 treatment groups for all outcomes and time intervals. The scores for the Western Ontario Rotator Cuff Index at 3 months were xylocaine = 45.4% +/- 13% and betamethasone = 56.3% +/- 17% (P = .13). At 6 months, the scores were xylocaine = 51% +/- 32% and betamethasone = 59% +/- 26% (P = .38). All other outcomes showed similar values. As well, similar results were found for 2 and 6 weeks after injection. Both groups showed improvement from baseline in all outcomes. With the numbers available for this study, the authors found betamethasone to be no more effective in improving the quality of life, range of motion, or impingement sign than xylocaine alone in patients with chronic rotator cuff tendinosis for all follow-up time intervals evaluated.


Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project.
Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well-characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well-understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.


Areas under peripheral pulse waves: a potential marker of atherosclerotic changes.
In this study, we propose a method for finding atherosclerotic changes based on the ratios of areas under peripheral arterial pulse wave (PW) contours and analyze its performance. The PW signals were recorded with force sensors and photoplethysmographic sensors from ankle, wrist, cubital fossa, index finger and second toe from 30 atherosclerotic patients and 52 control subjects. In addition, the day-to-day repeatability of the method was studied with 10 test subjects examined on three different days. The ratios of areas under the PWs were computed and the results were evaluated by means of receiver operating characteristic (ROC) analysis, intra-class correlation (ICC) coefficient and multiple linear regression analysis. Areas under ROC curves of 0.802-0.906 were found for different area ratios having statistically significant differences between the atheroslerotic group and control groups. ICCs over 0.80 were found widely for the beat-by-beat analyzed data and over 0.95 for the data based on the averages over different numbers of PWs. Multiple linear regression analysis showed linear dependence between the area ratios and age and the diagnosis of atherosclerosis. Our findings may facilitate development of novel diagnostic approaches and preventive strategies against cardiovascular disorders. However, further studies are needed to confirm the results. The presented study demonstrates the potential of arterial PW analysis in finding vascular abnormalities.


Poor-data and data-poor species stock assessment using a Bayesian hierarchical approach.
Appropriate inference for stocks or species with low-quality data (poor data) or limited data (data poor) is extremely important. Hierarchical Bayesian methods are especially applicable to small-area, small-sample-size estimation problems because they allow poor-data species to borrow strength from species with good-quality data. We used a hammerhead shark complex as an example to investigate the advantages of using hierarchical Bayesian models in assessing the status of poor-data and data-poor exploited species. The hammerhead shark complex (Sphyrna spp.) along the Atlantic and Gulf of Mexico coasts of the United States is composed of three species: the scalloped hammerhead (S. lewini), the great hammerhead (S. mokarran), and the smooth hammerhead (S. zygaena) sharks. The scalloped hammerhead comprises 70-80% of the catch and has catch and relative abundance data of good quality, whereas great and smooth hammerheads have relative abundance indices that are both limited and of low quality presumably because of low stock density and limited sampling. Four hierarchical Bayesian state-space surplus production models were developed to simulate variability in population growth rates, carrying capacity, and catchability of the species. The results from the hierarchical Bayesian models were considerably more robust than those of the nonhierarchical models. The hierarchical Bayesian approach represents an intermediate strategy between traditional models that assume different population parameters for each species and those that assume all species share identical parameters. Use of the hierarchical Bayesian approach is suggested for future hammerhead shark stock assessments and for modeling fish complexes with species-specific data, because the poor-data species can borrow strength from the species with good data, making the estimation more stable and robust.


Binding and suppression of the Myc transcriptional activation domain by p107.
An amino-terminal transactivation domain is required for Myc to function as a transcription factor controlling cell proliferation, differentiation, and apoptosis. A complementary DNA expression library was screened with a Myc fusion protein to identify proteins interacting with this domain, and a clone encoding the Rb-related p107 protein was isolated. The p107 protein was shown to associate with Myc in vivo and to suppress the activity of the Myc transactivation domain. However, mutant forms of Myc from Burkitt lymphoma cells, which contain sequence alterations in the transactivation domain, were resistant to p107-mediated suppression. Thus, disruption of a regulatory interaction between Myc and p107 may be important in tumorigenesis.


Socio-economic inequalities in smoking prevalence and involuntary exposure to tobacco smoke in Argentina: Analysis of three cross-sectional nationally representative surveys in 2005, 2009 and 2013.
Understanding patterns of socio-economic inequalities in tobacco consumption is key to design targeted public health policies for tobacco control. This study examines socio-economic inequalities in smoking and involuntary exposure to tobacco smoke between 2005 and 2013. Data were derived from the Argentine National Risk Factors Surveys, conducted in 2005, 2009, and 2013. Two inequality measures were calculated: the age-adjusted prevalence ratio (PR) and the disparity index (DI). Educational level, household income per consumer unit and employment status were used as proxies for socio-economic status (SES). Generalized linear models were used in the analysis. Prevalence of smoking decreased from 29.7% to 25.1% between 2005 and 2013, mainly in women (p<0.001). Despite the overall prevalence reduction, socio-economic inequalities in smoking persisted. For both men and women, the DI was moderately high for smoking (14.47%-33.06%) across the three surveys. In men, the PR indicated a higher smoking prevalence for lower educational levels and lower household income throughout the analyzed period. In women, unlike previous years, the 2013 survey showed disparity related to unemployment. Involuntary exposure to tobacco smoke in 2013 was associated with educational level and household income, with lower involuntary exposure among those with higher SES. While overall smoking rates have decreased in Argentina, socio-economic disparities related to tobacco smoking persist. Comprehensive tobacco control programs targeted to address these inequalities are essential in developing strategies to reduce health disparities in tobacco-related diseases.


Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA.
Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.


Dietary correlates of an at-risk BMI among Inuit adults in the Canadian high arctic: cross-sectional international polar year Inuit health survey, 2007-2008.
The study's objective was to investigate the dietary correlates of an at-risk body mass index (BMI) among Inuit adults from thirty-six communities across the Canadian Arctic using data from the cross-sectional International Polar Year Inuit Health Survey, conducted in 2007-2008. The survey included assessments of 24-hr dietary recall, sociodemographics, physical activity, and anthropometry. Dietary characteristics of overweight and obesity were similar and therefore combined into one at- risk BMI category (≥25 kg/m2) for analyses. The relationship between an at-risk BMI and energy intake from macronutrients, high sugar drinks, high-fat foods, saturated fatty acids, and traditional foods were examined entering each dietary variable separately into a logistic regression model as an independent variable. Analyses were adjusted for age, sex, region, kcalories, walking, smoking and alcohol consumption. Further multivariable models considered selected dietary variables together in one model. An at-risk BMI was present for 64% with a prevalence of overweight and obesity of 28% and 36%, respectively. Consumption of high-sugar drinks (>15.5% E) was significantly related with having an at-risk BMI (OR = 1.6; 95% CI 1.2; 2.2), whereas the % E from total carbohydrate evaluated as a continuous variable and as quartiles was inversely related to an at-risk BMI (P -trend < 0.05) in multivariable analyses. While % E from high-fat foods was positively related to an at-risk BMI, the findings were not significant in a model controlling for high-sugar drinks and % E from carbohydrates. The prevalence of overweight and obesity is of public health concern among Inuit. The current findings highlight the obesogenic potential of high-sugar drink consumption in an ethnically distinct population undergoing rapid cultural changes and raises concerns regarding carbohydrate restricted diets. Health promotion programs aimed at preventing the development of an unhealthy body weight should focus on physical activity and the promotion of healthy diets with reduced intake of sugar drinks.


Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force
We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.


A conservation checklist of the amphibians and reptiles of Sonora, Mexico, with updated species lists.
Sonora has a rich natural diversity, including reptiles and amphibians. Sonora's location on the United States-Mexico border creates some unique conservation challenges for its wildlife. We compiled a list of the amphibian and reptile species currently known for Sonora, summarized the conservation status of these species, and compared our list of species with known species lists for adjacent states. The herpetofauna of Sonora comprises 200 species of amphibians and reptiles (38 amphibians and 162 reptiles). Overall, Sonora shares the most species with Chihuahua, Sinaloa, and Arizona. Approximately 11% of the amphibian and reptile species are IUCN listed, but 35.5% are placed in a protected category by SEMARNAT, and 32.6% are categorized as high risk by the Environmental Vulnerability Score.


Evaluation of a plasmid-based transgenic mouse model for detecting in vivo mutations.
To study in vivo somatic mutations a C57BL/6 transgenic mouse model was constructed harboring multiple chromosomally integrated copies of the plasmid pUR288, which carried the lacZ reporter gene as the mutational target. We previously demonstrated that lacZ-containing plasmids could be rescued from their integrated state efficient enough to detect mutations in lacZ by positive selection. The smaller size of the plasmid vector, as compared with our earlier transgenic mouse model based on bacteriophage lambda vectors, should offer considerable advantages in terms of rescue efficiency and sensitivity to large size alterations in the lacZ gene. To evaluate the plasmid-based mouse model for its suitability to detect in vivo mutations, we determined mutant frequencies in different organs of untreated and ethyl nitrosourea (ENU)-treated animals using a new, improved protocol. The rescue efficiencies obtained were as high as 200,000/micrograms genomic DNA; millions of transformants could be obtained in one single experiment. The average spontaneous mutant frequency in four different organs of 4- to 8-week-old mice ranged from 4.41 to 6.82 x 10(-5), compared with a mutant frequency of the same plasmid grown in Escherichia coli of approximately 1 x 10(-5) or less. Single treatments with 100 and 250 mg ENU/kg body wt resulted in a 7- and 14-fold increase, respectively, in spleen mutant frequency at 14 days after i.p. administration of the alkylating agent. Restriction enzyme analysis showed that a considerable portion of spontaneous mutants were size changes varying from approximately 100 to 3000 bp. Some mutant plasmids contained mouse genomic sequences, which is indicative of large genetic rearrangement events involving the 3' flanking regions of the transgene cluster. Among the ENU-induced mutants, size changes comprised only a minor fraction of the total, which is in keeping with the known ENU mutation spectra in vitro and in vivo. The high rescue efficiency of this plasmid-based model, in combination with its sensitivity to a broad spectrum of mutations, including large deletions, makes it very suitable as a general in vivo mutagenicity test system.


Life Cycle Assessment of Urine Diversion and Conversion to Fertilizer Products at the City Scale.
Urine diversion has been proposed as an approach for producing renewable fertilizers and reducing nutrient loads to wastewater treatment plants. Life cycle assessment was used to compare environmental impacts of the operations phase of urine diversion and fertilizer processing systems [via (1) a urine concentration alternative and (2) a struvite precipitation and ion exchange alternative] at a city scale to conventional systems. Scenarios in Vermont, Michigan, and Virginia were modeled, along with additional sensitivity analyses to understand the importance of key parameters, such as the electricity grid and wastewater treatment method. Both urine diversion technologies had better environmental performance than the conventional system and led to reductions of 29-47% in greenhouse gas emissions, 26-41% in energy consumption, approximately half the freshwater use, and 25-64% in eutrophication potential, while acidification potential ranged between a 24% decrease to a 90% increase. In some situations, wastewater treatment chemical requirements were eliminated. The environmental performance improvement was usually dependent on offsetting the production of synthetic fertilizers. This study suggests that urine diversion could be applied broadly as a strategy for both improving wastewater management and decarbonization.


Deuteron NMR investigation on orientational order parameter in polymer dispersed liquid crystal elastomers.
Polymer-dispersed liquid crystal elastomers have been recently introduced as a thermomechanically active composite material, consisting of magnetically oriented liquid crystal elastomer particles incorporated in a cured polymer matrix. Their thermomechanical properties are largely governed by the degree of imprinted particle alignment, which can be assessed by means of deuterium perturbed 2H-NMR. Spectra of samples with various degrees of imprinted particle alignment were recorded and the results simulated using the discrete reorientational exchange model developed for determining the dispersion of liquid crystal elastomer's domain orientational distribution. We show that the model can be applied to measure the orientational distribution of embedded liquid crystal microparticles and successfully determine the orientational order parameter in the composite system. Thermomechanical measurements correlate well with the obtained results, thus additionally confirming the validity of the applied method.


A dangerous cocktail: Alcohol consumption increases suicidal ideations among problem gamblers in the general population.
The current research examined whether alcohol consumption exacerbates suicidal ideations among gamblers in the general population. While prior research suggests problem gambling severity and excessive alcohol consumption are unique predictors of suicidal behaviors, the extant literature as almost exclusively focused on gamblers in treatment. This represents a significant gap in the literature as less than 10% of gamblers seek treatment. Furthermore, gamblers in treatment are not representative of gamblers in the general population, precluding a simple generalization of research findings. We address this gap using data obtained from the Canadian Community Health Survey (Cycle 4.1)--a cross-sectional national survey that assesses health-related information among the Canadian population. To this end, we conducted a moderation analysis with problem gambling severity as the independent variable, weekly alcohol consumption as the moderator variable and suicidal ideations (in the past 12 months) as the dependent variable. The results found that alcohol consumption alone did not reliably predict suicidal ideation among gamblers who did not gamble problematically. However, as predicted, the odds of suicidal ideation were greatest among problem gamblers who frequently consumed alcohol. Thus, it may behoove policy makers to re-visit the availability of alcohol in gambling venues. Moreover, responsible gambling-oriented education initiatives may be advanced by informing gamblers about the increased risk of suicidal ideations when problematic gambling is combined with frequent alcohol consumption.


Pharmacological strategies for muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a fatal, genetic disorder whose relentless progression underscores the urgency for developing a cure. Although Duchenne initiated clinical trials roughly 150 years ago, therapies for DMD remain supportive rather than curative. A paradigm shift towards developing rational therapeutic strategies occurred with identification of the DMD gene. Gene- and cell-based therapies designed to replace the missing gene and/or dystrophin protein have achieved varying degrees of success. However, pharmacological strategies not designed to replace dystrophin per se appear promising, and can circumvent many hurdles hampering gene- and cell-based therapy. Here, we will review present pharmacological strategies, in particular those dealing with functional substitution of dystrophin by utrophin and enhancing muscle progenitor commitment by myostatin blockade, with a view toward facilitating drug discovery for DMD.


Regulation of cell-matrix contacts and beta-catenin signaling in VSMC by integrin-linked kinase: implications for intimal thickening.
Vascular smooth muscle cell (VSMC) proliferation and migration is responsible for intimal thickening that occurs in restenosis and atherosclerosis. Integrin-linked kinase (ILK) is a serine/threonine protein kinase implicated in signaling pathways involved in cell proliferation and migration. We studied the involvement of ILK in intimal thickening. ILK expression was significantly increased in two models of intimal thickening: balloon-injured rat carotid arteries and human saphenous vein organ cultures. Over-expression of a dominant negative ILK (DN-ILK) significantly reduced intimal thickening by approximately 50% in human saphenous vein organ cultures, demonstrating an important role in intimal thickening. ILK protein and activity was reduced on laminin and up-regulated on fibronectin, indicating ILK protein expression is modulated by extracellular matrix composition. Inhibition of ILK by siRNA knockdown and DN-ILK significantly decreased VSMC proliferation and migration while wild type ILK significantly increased proliferation and migration on laminin, confirming an essential role of ILK in both processes. Localization of paxillin and vinculin and protein levels of FAK and phospho-FAK indicated that inhibition of ILK reduced focal adhesion formation. Additionally, inhibition of ILK significantly attenuated the presence of the cell-cell complex proteins N-cadherin and beta-catenin, and beta-catenin signaling. We therefore suggest ILK modulates VSMC proliferation and migration at least in part by acting as a molecular scaffold in focal adhesions as well as modulating the stability of cell-cell contact proteins and beta-catenin signaling. In summary, ILK plays an important role in intimal thickening by modulating VSMC proliferation and migration via regulation of cell-matrix and cell-cell contacts and beta-catenin signaling.


[Mental disorders in Latin America and the Caribbean: a public health priority].
The growing burden of mental disorders in Latin America and the Caribbean has become too large to ignore. There is a need to know more about the prevalence of mental disorders and the gap between the number of individuals with psychiatric disorders and the number of those persons who remain untreated even though effective treatments exist. Having that knowledge would make it possible to improve advocacy, adopt better policies, formulate innovative intervention programs, and apportion resources commensurate with needs. Data were extracted from community-based psychiatric epidemiological studies published in Latin America and the Caribbean from 1980 through 2004 that used structured diagnostic instruments and provided prevalence rates. Estimates of the crude rates in Latin America and the Caribbean for the various disorders were determined by calculating the mean and median rates across the studies, by gender. In addition, data on service utilization were reviewed in order to calculate the treatment gap for specific disorders. Nonaffective psychosis (including schizophrenia) had an estimated mean one-year prevalence rate of 1.0%; major depression, 4.9%; and alcohol use abuse or dependence, 5.7%. Over one-third of individuals with nonaffective psychosis, over half of those with an anxiety disorder, and some three-fourths of those with alcohol use abuse or dependence did not receive mental health care from either specialized or general health services. The current treatment gap in mental health care in Latin America and the Caribbean remains wide. Further, current data likely greatly underestimate the number of untreated individuals. The epidemiological transition and changes in the population structure will further widen the treatment gap in Latin America and the Caribbean unless mental health policies are formulated or updated and programs and services are expanded.


Physicians' experiences with the Oregon Death with Dignity Act.
Physician-assisted suicide was legalized in Oregon in October 1997. There are data on patients who have received prescriptions for lethal medications and died after taking the medications. There is little information, however, on physicians' experiences with requests for assistance with suicide. Between February and August 1999, we mailed a questionnaire to physicians who were eligible to prescribe lethal medications under the Oregon Death with Dignity Act. Of 4053 eligible physicians, 2649 (65 percent) returned the survey. Of the respondents, 144 (5 percent) had received a total of 221 requests for prescriptions for lethal medications since October 1997. We received information on the outcome in 165 patients (complete information for 143 patients and partial for on an additional 22). The mean age of the patients was 68 years; 76 percent had an estimated life expectancy of less than six months. Thirty-five percent requested a prescription from another physician. Twenty-nine patients (18 percent) received prescriptions, and 17 (10 percent) died from administering the prescribed medication. Twenty percent of the patients had symptoms of depression; none of these patients received a prescription for a lethal medication. In the case of 68 patients, including 11 who received prescriptions and 8 who died by taking the prescribed medication, the physician implemented at least one substantive palliative intervention, such as control of pain or other symptoms, referral to a hospice program, a consultation, or a trial of antidepressant medication. Forty-six percent of the patients for whom substantive interventions were made changed their minds about assisted suicide, as compared with 15 percent of those for whom no substantive interventions were made (P<0.001). Our data indicate that in Oregon, physicians grant about 1 in 6 requests for a prescription for a lethal medication and that 1 in 10 requests actually result in suicide. Substantive palliative interventions lead some--but not all--patients to change their minds about assisted suicide.


Versatile synthesis of the signaling peptide glorin.
We present a versatile synthesis of the eukaryotic signaling peptide glorin as well as glorinamide, a synthetic analog. The ability of these compounds to activate glorin-induced genes in the social amoeba Polysphondylium pallidum was evaluated by quantitative reverse transcription PCR, whereby both compounds showed bioactivity comparable to a glorin standard. This synthetic route will be useful in conducting detailed structure-activity relationship studies as well as in the design of chemical probes to dissect glorin-mediated signaling pathways.


A high-resolution assessment of climate change impact on water footprints of cereal production in India.
Water footprint (WF), a comprehensive indicator of water resources appropriation, has evolved as an efficient tool to improve the management and sustainability of water resources. This study quantifies the blue and green WF of major cereals crops in India using high resolution soil and climatic datasets. A comprehensive modelling framework, consisting of Evapotranspiration based Irrigation Requirement (ETIR) tool, was developed for WF assessment. For assessing climate change impact on WF, multi-model ensemble climate change scenarios were generated using the hybrid-delta ensemble method for RCP4.5 and RCP6.0 and future period of 2030s and 2050s. The total WF of the cereal crops are projected to change in the range of - 3.2 to 6.3% under different RCPs in future periods. Although, the national level green and blue WF is projected to change marginally, distinct trends were observed for Kharif (rainy season-June to September) and rabi (winter season-October to February) crops. The blue WF of paddy is likely to decrease by 9.6%, while for wheat it may increase by 4.4% under RCP4.5 during 2050s. The green WF of rabi crops viz. wheat and maize is likely to increase in the range of 20.0 to 24.1% and 9.9 to 16.2%, respectively. This study provides insights into the influences of climate change on future water footprints of crop production and puts forth regional strategies for future water resource management. In view of future variability in the WFs, a water footprint-based optimization for relocation of crop cultivation areas with the aim of minimising the blue water use would be possible management alternative.


Biohydrogen production by dark fermentation of glycerol using Enterobacter and Citrobacter Sp.
Glycerol is an attractive substrate for biohydrogen production because, in theory, it can produce 3 mol of hydrogen per mol of glycerol. Moreover, glycerol is produced in substantial amounts as a byproduct of producing biodiesel, the demand for which has increased in recent years. Therefore, hydrogen production from glycerol was studied by dark fermentation using three strains of bacteria: namely, Enterobacter spH1, Enterobacter spH2, and Citrobacter freundii H3 and a mixture thereof (1:1:1). It was found that, when an initial concentration of 20 g/L of glycerol was used, all three strains and their mixture produced substantial amounts of hydrogen ranging from 2400 to 3500 mL/L, being highest for C. freundii H3 (3547 mL/L) and Enterobacter spH1 (3506 mL/L). The main nongaseous fermentation products were ethanol and acetate, albeit in different ratios. For Enterobacter spH1, Enterobacter spH2, C. freundii H3, and the mixture (1:1:1), the ethanol yields (in mol EtOH/mol glycerol consumed) were 0.96, 0.67, 0.31, and 0.66, respectively. Compared to the individual strains, the mixture (1:1:1) did not show a significantly higher hydrogen level, indicating that there was no synergistic effect. Enterobacter spH1 was selected for further investigation because of its higher yield of hydrogen and ethanol.


Teaching about teaching and instruction on instruction: a challenge for health sciences library education.
This is a review of the master's-level curricula of the fifty-eight America Library Association-accredited library and information science programs and iSchools for evidence of coursework and content related to library instruction. Special emphasis is placed on the schools and programs that also offer coursework in medical or health sciences librarianship. Fifty-eight school and program websites were reviewed. Course titles and course descriptions for seventy-three separate classes were analyzed. Twenty-three syllabi were examined. All North American library education programs offer at least one course in the general area of library instruction; some programs offer multiple courses. No courses on instruction, however, are focused directly on the specialized area of health sciences librarianship. Master's degree students can take appropriate classes on library instruction, but the medical library profession needs to offer continuing education opportunities for practitioners who want to have specific instruction for the specialized world of the health sciences.


Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers.
Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of α-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography-mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating β-carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive β-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant β-carotene among men not taking β-carotene supplements should be interpreted cautiously, as they are likely due to chance.


Comparison of next-generation portable pollution monitors to measure exposure to PM2.5 from household air pollution in Puno, Peru.
Assessment of personal exposure to PM2.5 is critical for understanding intervention effectiveness and exposure-response relationships in household air pollution studies. In this pilot study, we compared PM2.5 concentrations obtained from two next-generation personal exposure monitors (the Enhanced Children MicroPEM or ECM; and the Ultrasonic Personal Air Sampler or UPAS) to those obtained with a traditional Triplex Cyclone and SKC Air Pump (a gravimetric cyclone/pump sampler). We co-located cyclone/pumps with an ECM and UPAS to obtain 24-hour kitchen concentrations and personal exposure measurements. We measured Spearmen correlations and evaluated agreement using the Bland-Altman method. We obtained 215 filters from 72 ECM and 71 UPAS co-locations. Overall, the ECM and the UPAS had similar correlation (ECM ρ = 0.91 vs UPAS ρ = 0.88) and agreement (ECM mean difference of 121.7 µg/m3 vs UPAS mean difference of 93.9 µg/m3 ) with overlapping confidence intervals when compared against the cyclone/pump. When adjusted for the limit of detection, agreement between the devices and the cyclone/pump was also similar for all samples (ECM mean difference of 68.8 µg/m3 vs UPAS mean difference of 65.4 µg/m3 ) and personal exposure samples (ECM mean difference of -3.8 µg/m3 vs UPAS mean difference of -12.9 µg/m3 ). Both the ECM and UPAS produced comparable measurements when compared against a cyclone/pump setup.


Brain response to working memory over three years of adolescence: influence of initiating heavy drinking.
Many adolescents engage in heavy alcohol use. The aim of this study was to disentangle whether brain abnormalities seen in adolescent heavy drinkers are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. Study 1 used cross-sectional functional magnetic resonance imaging (fMRI) visual working-memory (VWM) data from 15- to 19-year-olds (20 heavy drinkers, 20 controls) to identify brain regions affected by heavy adolescent alcohol use. Study 2 used longitudinal fMRI VWM data from 12- to 16-year-olds imaged before the onset of drinking and imaged again on the same scanner approximately 3 years later. Those who had transitioned into heavy drinking (n = 20) were matched to continuous nondrinkers (n = 20) on baseline alcohol risk and developmental factors (N = 40; 80 scans). Study 1 found that heavy drinkers exhibited more frontal and parietal but less occipital activation than controls, defining the regions of interest for Study 2. In Study 2, adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers, which increased after the onset of heavy drinking, in frontal (1,431 μL, p = .003; η² = .19) and parietal (810 μL, p = .005; η²= .23) regions, as in Study 1. Lower baseline activation in the frontal and parietal regions predicted subsequent substance use, more so than commonly observed predictors of youth drinking (p < .05). Adolescents who initiated heavy drinking showed different brain activation before the onset of drinking, then less efficient information processing after high-dose alcohol use started. This suggests neural response patterns that could be risk factors for future substance use and also supports prior neuropsychological reports indicating that initiating heavy episodic drinking in adolescence may be followed by subtle alterations in brain functioning.


Compression-induced changes in the shape and volume of the chondrocyte nucleus.
Changes in cell shape and volume are believed to play a role in the process of mechanical signal transduction by chondrocytes in articular cartilage. One proposed pathway through which chondrocyte deformation may be transduced to an intracellular signal is through cytoskeletally mediated deformation of intracellular organelles, and more specifically, of the cell nucleus. In this study, confocal scanning laser microscopy was used to perform in situ three-dimensional morphometric analyses of the nuclei of viable chondrocytes during controlled compression of articular cartilage explants from the canine patellofemoral groove. Unconfined compression of the tissue to a 15% surface-to-surface strain resulted in a significant decrease of chondrocyte height and volume by 14.7 +/- 6.4 and 11.4 +/- 8.4%, respectively, and of nuclear height and volume by 8.8 +/- 6.2% and 9.8 +/- 8.8%, respectively. Disruption of the actin cytoskeleton using cytochalasin D altered the relationship between matrix deformation and changes in nuclear height and shape, but not volume. The morphology and deformation behavior of the chondrocytes were not affected by cytochalasin treatment. These results suggest that the actin cytoskeleton plays an important role in the link between compression of the extracellular matrix and deformation of the chondrocyte nuclei and imply that chondrocytes and their nuclei undergo significant changes in shape and volume in vivo.


A pulse of mid-Pleistocene rift volcanism in Ethiopia at the dawn of modern humans.
The Ethiopian Rift Valley hosts the longest record of human co-existence with volcanoes on Earth, however, current understanding of the magnitude and timing of large explosive eruptions in this region is poor. Detailed records of volcanism are essential for interpreting the palaeoenvironments occupied by our hominin ancestors; and also for evaluating the volcanic hazards posed to the 10 million people currently living within this active rift zone. Here we use new geochronological evidence to suggest that a 200 km-long segment of rift experienced a major pulse of explosive volcanic activity between 320 and 170 ka. During this period, at least four distinct volcanic centres underwent large-volume (>10 km3) caldera-forming eruptions, and eruptive fluxes were elevated five times above the average eruption rate for the past 700 ka. We propose that such pulses of episodic silicic volcanism would have drastically remodelled landscapes and ecosystems occupied by early hominin populations.


Enhanced photon collection enables four dimensional fluorescence nanoscopy of living systems.
The theoretically unlimited spatial resolution of fluorescence nanoscopy often comes at the expense of time, contrast and increased dose of energy for recording. Here, we developed MoNaLISA, for Molecular Nanoscale Live Imaging with Sectioning Ability, a nanoscope capable of imaging structures at a scale of 45-65 nm within the entire cell volume at low light intensities (W-kW cm-2). Our approach, based on reversibly switchable fluorescent proteins, features three distinctly modulated illumination patterns crafted and combined to gain fluorescence ON-OFF switching cycles and image contrast. By maximizing the detected photon flux, MoNaLISA enables prolonged (40-50 frames) and large (50 × 50 µm2) recordings at 0.3-1.3 Hz with enhanced optical sectioning ability. We demonstrate the general use of our approach by 4D imaging of organelles and fine structures in epithelial human cells, colonies of mouse embryonic stem cells, brain cells, and organotypic tissues.


Two-dimensional aperture coding for magnetic sector mass spectrometry.
In mass spectrometer design, there has been a historic belief that there exists a fundamental trade-off between instrument size, throughput, and resolution. When miniaturizing a traditional system, performance loss in either resolution or throughput would be expected. However, in optical spectroscopy, both one-dimensional (1D) and two-dimensional (2D) aperture coding have been used for many years to break a similar trade-off. To provide a viable path to miniaturization for harsh environment field applications, we are investigating similar concepts in sector mass spectrometry. Recently, we demonstrated the viability of 1D aperture coding and here we provide a first investigation of 2D coding. In coded optical spectroscopy, 2D coding is preferred because of increased measurement diversity for improved conditioning and robustness of the result. To investigate its viability in mass spectrometry, analytes of argon, acetone, and ethanol were detected using a custom 90-degree magnetic sector mass spectrometer incorporating 2D coded apertures. We developed a mathematical forward model and reconstruction algorithm to successfully reconstruct the mass spectra from the 2D spatially coded ion positions. This 2D coding enabled a 3.5× throughput increase with minimal decrease in resolution. Several challenges were overcome in the mass spectrometer design to enable this coding, including the need for large uniform ion flux, a wide gap magnetic sector that maintains field uniformity, and a high resolution 2D detection system for ion imaging. Furthermore, micro-fabricated 2D coded apertures incorporating support structures were developed to provide a viable design that allowed ion transmission through the open elements of the code.


Brief Report: Durability of the Effect of Financial Incentives on HIV Viral Load Suppression and Continuity in Care: HPTN 065 Study.
Results from the HPTN 065 study showed that financial incentives (FI) were associated with significantly higher viral load suppression and higher levels of engagement in care among patients at HIV care sites randomized to FI versus sites randomized to standard of care (SOC). We assessed HIV viral suppression and continuity in care after intervention withdrawal to determine the durability of FI on these outcomes. A total of 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, participated in the study. Laboratory data reported to the US National HIV Surveillance System were used to determine site-level viral suppression and continuity in care outcomes. Postintervention effects were assessed for the 3 quarters after discontinuation of FI. Generalized estimation equations were used to compare FI and SOC site-level outcomes after intervention withdrawal. After FI withdrawal, a trend remained for an increase in viral suppression by 2.7% (-0.3%, 5.6%, P = 0.076) at FI versus SOC sites, decreasing from the 3.8% increase noted during implementation of the intervention. The significant increase in continuity in care during the FI intervention was sustained after intervention with 7.5% (P = 0.007) higher continuity in care at FI versus SOC sites. After the withdrawal of FI, findings at the 9-months postintervention withdrawal from this large study showed evidence of durable effects of FI on continuity in care, with trend for continued higher viral suppression. These findings are promising for adoption of such interventions to enhance key HIV-related care outcomes.


Regulation of human aldoketoreductase 1C3 (AKR1C3) gene expression in the adipose tissue.
Aldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.


Early Alpine occupation backdates westward human migration in Late Glacial Europe.
Before the end of the Last Glacial Maximum (LGM, ∼16.5 ka ago)1 set in motion major shifts in human culture and population structure,2 a consistent change in lithic technology, material culture, settlement pattern, and adaptive strategies is recorded in Southern Europe at ∼18-17 ka ago. In this time frame, the landscape of Northeastern Italy changed considerably, and the retreat of glaciers allowed hunter-gatherers to gradually recolonize the Alps.3-6 Change within this renewed cultural frame (i.e., during the Late Epigravettian phase) is currently associated with migrations favored by warmer climate linked to the Bølling-Allerød onset (14.7 ka ago),7-11 which replaced earlier genetic lineages with ancestry found in an individual who lived ∼14 ka ago at Riparo Villabruna, Italy, and shared among different contexts (Villabruna Cluster).9 Nevertheless, these dynamics and their chronology are still far from being disentangled due to fragmentary evidence for long-distance interactions across Europe.12 Here, we generate new genomic data from a human mandible uncovered at Riparo Tagliente (Veneto, Italy), which we directly dated to 16,980-16,510 cal BP (2σ). This individual, affected by focal osseous dysplasia, is genetically affine to the Villabruna Cluster. Our results therefore backdate by at least 3 ka the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød event. In light of the new genetic evidence, this population replacement chronologically coincides with the very emergence of major cultural transitions in Southern and Western Europe.


Cost-effectiveness of the Australian National Tobacco Campaign.
The Australian National Tobacco Campaign (NTC) was an intensive mass media anti-smoking campaign, the first phase of which commenced in 1997, cost around $A9 million, and reduced smoking prevalence by 1.4%. To assess the cost-effectiveness of phase one of the NTC, which ran from June to November 1997. The quit benefits model (QBM), a Markov-cycle simulation model was used to predict the benefits of smoking cessation for the estimated 190 000 quitters from the time of quitting until death, censored at age 85 years. Measures of effectiveness were cases of lung cancer, acute myocardial infarction (AMI), stroke and chronic obstructive pulmonary disease (COPD) avoided; deaths prevented, and life-years and quality-adjusted life-years (QALYs) gained. The savings in healthcare costs through prevention of the four specified smoking-associated diseases were estimated. Future costs, life-years and QALYS were discounted at 3% per year. The QBM predicted that the NTC avoided over 32 000 cases of COPD, 11 000 cases of AMI, 10 000 cases of lung cancer, and 2500 cases of stroke. Prevention of around 55 000 deaths, gains of 323 000 life-years and 407 000 QALYs, and healthcare cost savings of $A740.6 million were predicted. The NTC was therefore both cost saving and effective. As well as reducing smoking prevalence, the NTC was unequivocally cost-effective.


Surgical Correction of Cicatricial Lower Eyelid Retraction: A Systematic Review.
Cicatricial lower eyelid retraction is a challenging condition. It involves scarring of the lower eyelid, which causes it to retract and expose the sclera. This can lead to complications such as dry eye syndrome and corneal melting. It can be caused by trauma, burns, or previous eyelid surgery. Detailed assessment and understanding of eyelid anatomy and retraction are critical for successful surgical planning. Dynamic and static examinations of the eyelid including measurements of the lower eyelid margin reflex distance (MRD2) and scleral show are also essential to determine the appropriate treatment approach. A systematic review was conducted using Medline, Scopus, and Cochrane databases with keywords related to cicatricial lower eyelid retraction. The publication language was limited to English after 2000. A total of 29 articles were included for data extraction and analysis. The main surgical techniques include tarsoconjunctival grafts, spacers, midface lift, and lateral canthal tendon suspension, although no single procedure has been universally recognized as the gold standard. New innovations such as synthetic grafts and xenografts are being explored for their potential in eyelid reconstruction. Severe cases, defined as those with inferior scleral show greater than 2 mm, may require a combination of reconstruction methods. Correcting cicatricial lower eyelid retraction is a major challenge in oculoplastic reconstruction. The surgical approach should be individualized, considering the pathologies and etiologies of lid retraction. In-depth knowledge and careful surgical planning are essential for best outcomes. There is no gold standard technique, and postoperative outcomes, complications, and management vary depending on the surgical approach used.


How informative is Wright's estimator of the number of genes affecting a quantitative character?
S. Wright suggested an estimator, m, of the number of loci, m, contributing to the difference in a quantitative character between two differentiated populations, which is calculated from the phenotypic means and variances in the two parental populations and their F1 and F2 hybrids. The same method can also be used to estimate m contributing to the genetic variance within a single population, by using divergent selection to create differentiated lines from the base population. In this paper we systematically examine the utility and problems of this technique under the influences of unequal allelic effects and initial allele frequencies, and linkage, which are known to lead m to underestimate m. In addition, we examine the effects of population size and selection intensity during the generations of selection. During selection, the estimator m rapidly approaches its expected value at the selection limit. With reasonable assumptions about unequal allelic effects and initial allele frequencies, the expected value of m without linkage is likely to be on the order of one-third of the number of genes. The estimates suffer most seriously from linkage. The practical maximum expectation of m is just about the number of chromosomes, considerably less than the "recombination index" which has been assumed to be the upper limit. The estimates are also associated with large sampling variances. An estimator of the variance of m derived by R. Lande substantially underestimates the actual variance. Modifications to the method can ameliorate some of the problems. These include using F3 or later generation variances or the genetic variance in the base population, and replicating the experiments and estimation procedure. However, even in the best of circumstances, information from m is very limited and can be misleading.


An injectable double-network hydrogel for the co-culture of vascular endothelial cells and bone marrow mesenchymal stem cells for simultaneously enhancing vascularization and osteogenesis.
The achievement of rapid vascularization in large implanted constructs is a major challenge in the field of bone tissue engineering. Although co-culture of bone-forming cells and vascular endothelial cells (VECs) has been expected to be a way of promoting vascularization during bone formation with a scaffold, there is a lack of detailed knowledge about the direct interactions between two types of stem cells in a three-dimensional (3D) extracellular matrix (ECM). Herein, we report on the use of an injectable cytocompatible double-network (DN) hydrogel to encapsulate, co-culture and subsequently stimulate the angiogenic/osteogenic differentiation of VECs and the human bone marrow mesenchymal stem cells (BM-MSCs), which demonstrates that the direct co-cultured system enables simultaneous enhancement of vascularization and osteogenesis by providing 3D cell-cell communication. Besides, the improved mechanical properties and the injectability of the DN hydrogel allow the delivery, long-time implantation, proliferation and differentiation of stem cells in vivo. Therefore, this study could provide a niche-like native ECM for stem cell survival and the regulation of the differentiation of multiple cell lines which will benefit bone repair.


Suppression of allergen-induced airway inflammation and immune response by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate.
In the present study, we have assessed the effect of the peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist fenofibrate on allergen-induced airway inflammation and immune response. C57BL/6 or PPARalpha knock-out (PPARalpha(-/-)) mice were sensitized with ovalbumin and challenged with ovalbumin alone or with ovalbumin+lipopolysaccharides. Fenofibrate was administered to allergen-exposed animals during challenge only or from the day prior to sensitization to the end of challenge. Inflammation and immune response were assessed by determining cell counts and cytokine levels in bronchoalveolar lavage fluids, expression of the transcription factors Gata-3 and T-bet in lung tissue and ovalbumin-specific IgE and IgG2a in serum. Treatment with fenofibrate (0.15-15 mg/day) during allergen challenge dose-dependently reduced airway inflammatory cell infiltrate induced by ovalbumin in C57BL/6 mice. Reduction reached 74.3% (P<0.001) in animals treated with 15 mg/day of the PPARalpha agonist, whereas this treatment failed to suppress cell infiltrate induced by allergen in PPARalpha(-/-) mice. In addition, when administered from the day prior to sensitization to the end of challenge, fenofibrate (15 mg/day) triggered switching of the immune response to allergen towards a Th1 profile, as evidenced by an increase in IgG2a levels, a reduction in IL(interleukin)-4 and IL-5 together with an increase in interferon-gamma, and a decrease in Gata-3/T-bet expression ratio. Upon challenge with ovalbumin+lipopolysaccharides, sensitized mice developed a severe inflammatory response characterized by infiltration of eosinophils, neutrophils, lymphocytes and macrophages and by increased release of IL-4, IL-5, tumor necrosis factor-alpha, macrophage-inflammatory protein-2 and monocyte chemoattractant protein-1. Administration of fenofibrate during allergen challenge dramatically reduced all responses. In conclusion, our data clearly demonstrate that fenofibrate exhibits an anti-inflammatory activity in allergic asthma, including in severe conditions, and that the PPARalpha agonist is also capable of switching the immune response to allergen towards a Th1 profile when given from the day prior to sensitization.


Early warning systems for malaria in Africa: from blueprint to practice.
Although the development of early warning systems for malaria has been advocated by international agencies and academic researchers for many years, practical progress in this area has been relatively modest. In two recent articles, Thomson et al. provide new evidence that models of malaria incidence that incorporate monitored or predicted climate can provide early warnings of epidemics one to five months in advance in semi-arid areas. Although the potential benefits of these models in terms of improved management of epidemics are clear, several technical and practical hurdles still need to be overcome before the models can be widely integrated into routine malaria-control strategies.


Intercellular communication is cell cycle modulated during early Xenopus laevis development.
We investigated intercellular communication during the seventh and tenth cell cycles of Xenopus laevis development using microinjection of Lucifer yellow and FITC-dextran as well as freeze-fracture electron microscopy. We found that gap junction-mediated dye coupling visualized using Lucifer yellow was strongly cell cycle modulated in the tenth cell cycle. Cytoplasmic bridge-mediated dye coupling visualized via FITC-dextran was also, of course, cell cycle modulated. The basis of cell cycle-modulated gap junctional coupling was investigated by measuring the abundance of morphologically detectable gap junctions through the tenth cell cycle. These proved to be six times more abundant at the beginning than at the end of this cell cycle.


True near field versus contrast near field imaging.
We demonstrate that in near field imaging, interaction between light and sample can be divided into two main areas: the true near field and the contrast near field domain. We performed extensive numerical simulations in order to identify the limits of these areas, and to investigate contrast near field imaging in which much easier propagation calculation can be achieved. Finally, we show an application with terahertz axonal imaging.


A combined planning and self-efficacy intervention to promote physical activity: a multiple mediation analysis.
Many individuals are motivated to improve their physical activity levels, but often fail to act upon their intention. Interventions fostering volitional strategies, such as action planning, coping planning, and self-efficacy beliefs, can help to translate intentions into behavior. This study examines the effectiveness and the mechanisms of a combined planning and self-efficacy intervention to promote physical activity among motivated individuals. Participants (N = 883) were randomly assigned to the intervention or to a waiting-list control condition. Multivariate analysis of variance revealed that the intervention resulted in significantly more physical activity, higher levels of action planning, coping planning, and volitional self-efficacy beliefs (p < 0.01). In addition, multiple mediation analysis showed that action planning, coping planning, and volitional self-efficacy mediate between the intervention and physical activity. The study shows that the intervention successfully fostered physical activity and unfolds the underlying self-regulatory mechanisms of the intervention's effectiveness.


Cortico-muscular coupling to control a hybrid brain-computer interface for upper limb motor rehabilitation: A pseudo-online study on stroke patients.
Brain-Computer Interface (BCI) systems for motor rehabilitation after stroke have proven their efficacy to enhance upper limb motor recovery by reinforcing motor related brain activity. Hybrid BCIs (h-BCIs) exploit both central and peripheral activation and are frequently used in assistive BCIs to improve classification performances. However, in a rehabilitative context, brain and muscular features should be extracted to promote a favorable motor outcome, reinforcing not only the volitional control in the central motor system, but also the effective projection of motor commands to target muscles, i.e., central-to-peripheral communication. For this reason, we considered cortico-muscular coupling (CMC) as a feature for a h-BCI devoted to post-stroke upper limb motor rehabilitation. In this study, we performed a pseudo-online analysis on 13 healthy participants (CTRL) and 12 stroke patients (EXP) during executed (CTRL, EXP unaffected arm) and attempted (EXP affected arm) hand grasping and extension to optimize the translation of CMC computation and CMC-based movement detection from offline to online. Results showed that updating the CMC computation every 125 ms (shift of the sliding window) and accumulating two predictions before a final classification decision were the best trade-off between accuracy and speed in movement classification, independently from the movement type. The pseudo-online analysis on stroke participants revealed that both attempted and executed grasping/extension can be classified through a CMC-based movement detection with high performances in terms of classification speed (mean delay between movement detection and EMG onset around 580 ms) and accuracy (hit rate around 85%). The results obtained by means of this analysis will ground the design of a novel non-invasive h-BCI in which the control feature is derived from a combined EEG and EMG connectivity pattern estimated during upper limb movement attempts.


Interaction and self-correction.
In this paper, I address the question of how to account for the normative dimension involved in conceptual competence in a naturalistic framework. First, I present what I call the naturalist challenge (NC), referring to both the phylogenetic and ontogenetic dimensions of conceptual possession and acquisition. I then criticize two models that have been dominant in thinking about conceptual competence, the interpretationist and the causalist models. Both fail to meet NC, by failing to account for the abilities involved in conceptual self-correction. I then offer an alternative account of self-correction that I develop with the help of the interactionist theory of mutual understanding arising from recent developments in phenomenology and developmental psychology.


Nightmares in the general population: identifying potential causal factors.
Nightmares are inherently distressing, prevent restorative sleep, and are associated with a number of psychiatric problems, but have rarely been the subject of empirical study. Negative affect, linked to stressful events, is generally considered the key trigger of nightmares; hence nightmares have most often been considered in the context of post-traumatic stress disorder (PTSD). However, many individuals with heightened negative affect do not have nightmares. The objective of this study was to identify mechanistically plausible factors, beyond negative affect, that may explain why individuals experience nightmares. 846 participants from the UK general population completed an online survey about nightmare occurrence and severity (pre-occupation, distress, and impairment), negative affect, worry, depersonalisation, hallucinatory experiences, paranoia, alcohol use, sleep duration, physical activity levels, PTSD symptoms, and stressful life events. Associations of nightmares with the putative predictive factors were tested controlling for levels of negative affect. Analyses were also repeated controlling for levels of PTSD and the recent occurrence of stressful life events. Nightmare occurrence, adjusting for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, paranoia, and sleep duration (odds ratios 1.25-1.45). Nightmare severity, controlling for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, and paranoia (R 2s: 0.33-0.39). Alcohol use and physical activity levels were not associated with nightmares. The study identifies a number of potential predictors of the occurrence and severity of nightmares. Causal roles require testing in future longitudinal, experimental, and treatment studies.


Stability of extemporaneously prepared oxandrolone oral suspensions.
The stability of extemporaneously prepared oxandrolone oral suspensions was studied. Oxandrolone oral suspension (1 mg/mL) was prepared using oxandrolone tablets, Ora-Plus, and either Ora-Sweet or Ora-Sweet SF. Three identical samples of each formulation were prepared and stored in 2-oz amber plastic bottles with child-resistant caps at room temperature (23-25 °C). After thorough but gentle shaking by hand to prevent foaming, a 1-mL sample was withdrawn from each of the six bottles, diluted with mobile phase to an expected concentration of 200 μg/mL, and assayed in duplicate by injecting 5 μL into the high-performance liquid chromatography system immediately after preparation and at 7, 14, 35, 60, and 90 days. The samples were examined for any change in color or pH on each day of analysis. The stability of the suspensions was determined by calculating the percentage of the initial oxandrolone concentration remaining on each test day. Stability was defined as the retention of at least 90% of the initial oxandrolone concentration. At least 98% of the original oxandrolone concentration remained in both formulations at the end of the 90-day study period. There was no appreciable change in odor, taste, color, or pH. Both suspensions remained white in color and sweet with no aftertaste throughout the study period. The oxandrolone was easily resuspended with gentle shaking. Extemporaneously prepared suspensions of oxandrolone 1 mg/mL in 1:1 mixtures of Ora-Plus and either Ora-Sweet or Ora-Sweet SF were stable for at least 90 days when stored in 2-oz amber plastic bottles at room temperature.


Opioid Use Following Operatively Treated Pediatric Elbow and Femur Fractures.
Opioids are a commonly utilized component of pain management following pediatric extremity fractures, yet an increasing number of adolescents and children are falling victim to their negative effects. The purpose of this study was to examine opioid use in the pediatric fracture population by determining and comparing the average hospital opioid dosage utilized in the operative pediatric elbow and femur fractures and determining and comparing the average dose prescribed following operative treatment of elbow and femur fractures. All elbow and femur fractures treated operatively between January and December 2016 were identified. Patients aged 0 to 17 years with closed injuries who presented to the emergency department (ED) within 24 hours of injury and underwent operative treatment were included. Demographic information, opioid and nonopioid analgesic medication doses administered in the ED and while inpatient, and postdischarge prescription information were recorded. Opioid doses were converted to oral morphine equivalents. In total, 91.9% and 78.1% of patients received opioids during the ED and inpatient periods, respectively. Only 30% of patients in either cohort received a nonopioid analgesic in the ED and only 44% received ibuprofen while inpatient. Average total opioid dose per hour of hospital stay was not significantly different between elbow fracture and femur fracture cohorts, which was unexpected. There was no significant difference between the average opioid dose or number of doses prescribed for postdischarge use between cohorts. This study provides data on average hospital opioid and nonopioid use following pediatric elbow and femur fractures. The results reveal inconsistent nonopioid analgesic use and similar hospital opioid use in elbow and femur fracture patients. This study provides baseline analgesic use data for future investigations. Level IV.


A female Viking warrior confirmed by genomics.
The objective of this study has been to confirm the sex and the affinity of an individual buried in a well-furnished warrior grave (Bj 581) in the Viking Age town of Birka, Sweden. Previously, based on the material and historical records, the male sex has been associated with the gender of the warrior and such was the case with Bj 581. An earlier osteological classification of the individual as female was considered controversial in a historical and archaeological context. A genomic confirmation of the biological sex of the individual was considered necessary to solve the issue. Genome-wide sequence data was generated in order to confirm the biological sex, to support skeletal integrity, and to investigate the genetic relationship of the individual to ancient individuals as well as modern-day groups. Additionally, a strontium isotope analysis was conducted to highlight the mobility of the individual. The genomic results revealed the lack of a Y-chromosome and thus a female biological sex, and the mtDNA analyses support a single-individual origin of sampled elements. The genetic affinity is close to present-day North Europeans, and within Sweden to the southern and south-central region. Nevertheless, the Sr values are not conclusive as to whether she was of local or nonlocal origin. The identification of a female Viking warrior provides a unique insight into the Viking society, social constructions, and exceptions to the norm in the Viking time-period. The results call for caution against generalizations regarding social orders in past societies.


'The nurse did not even greet me': how informed versus non-informed patients evaluate health systems responsiveness in South Africa.
Universal Health Coverage is not only about access to health services but also about access to high-quality care, since poor experiences may deter patients from accessing care. Evidence shows that quality of care drives health outcomes, yet little is known about non-clinical dimensions of care, and patients' experience thereof relative to satisfaction with visits. This paper investigates the role of non-clinical dimensions of care in patient satisfaction. Our study describes the interactions of informed and non-informed patients with primary healthcare workers at 39 public healthcare facilities in two metropolitan centres in two South African provinces. Our analysis included 1357 interactions using standardised patients (for informed patients) and patients' exit interviews (for non-informed patients). The data were combined for three types of visits: contraception, hypertension and tuberculosis. We describe how satisfaction with care was related to patients' experiences of non-clinical dimensions. We show that when real patients (RPs) reported being satisfied (vs dissatisfied) with a visit, it was associated with a 30% increase in the probability that a patient is greeted at the facilities. Likewise, when the RPs reported being satisfied (vs dissatisfied) with the visit, it was correlated with a 15% increase in the prospect that patients are pleased with healthcare workers' explanations of health conditions. Informed patients are better equipped to assess health-systems responsiveness in healthcare provision. Insights into responsiveness could guide broader efforts aimed at targeted education and empowerment of primary healthcare users to strengthen health systems and shape expectations for appropriate care and conduct.