Importance of waste stabilization ponds and wastewater irrigation in the generation of vector mosquitoes in Pakistan.
The objective of the current study was to investigate the role of waste stabilization ponds (WSP) and wastewater-irrigated sites for the production of mosquitoes of medical importance. Mosquito larvae were collected fortnightly from July 2001 to June 2002 in Faisalabad, Pakistan. In total, 3,132 water samples from WSP and irrigated areas yielded 606,053 Culex larvae of five species. In addition, 107,113 anophelines, representing eight species were collected. Anopheles subpictus (Grassi) and Culex mosquitoes, especially Culex quinquefasciatus (Say) and Culex tritaeniorhynchus (Giles), showed an overwhelming preference for anaerobic ponds, which receive untreated wastewater. Facultative ponds generated lower numbers of both Anopheles and Culex mosquitoes, whereas the last ponds in the series, the maturation ponds, were the least productive for both mosquito genera. An. subpictus and Anopheles stephensi (Liston) were the dominant Anopheles species in wastewater-irrigated sites, with Anopheles culicifacies (Giles) recorded in low numbers. This was also the pattern in nearby sites, irrigated with river water. Among the Culex species, Cx. tritaeniorhynchus was by far the most frequently recorded in both wastewater- and river water-irrigated sites with Cx. quinquefasciatus as the second most abundant species but restricted to wastewater-irrigated areas. Univariate logistic regression analysis showed that presence of An. subpictus and Culex mosquitoes was significantly associated with emergent grass vegetation and low salinity. Regular removal of emergent grass along the margins of the anaerobic ponds and changes in the concrete design of the ponds are likely to reduce the mosquito production, especially of Culex species.


Valsalva maneuver procedures in the diagnosis of right-to-left shunt by contrast-enhanced transcranial doppler using agitated saline solution with blood as a contrast agent.
To compare two different timings for the performance of the Valsalva maneuver (VM) using an infusion of agitated saline solution with blood as contrast agent (CA) to right-to-left shunt (RLS) screening. 42 patients were submitted to a standardized contrast-enhanced transcranial doppler (cTCD) to screen for right-to-left shunt (RLS). cTCD technique was done with two different moments of the VM: [1] the CA injection during the VM (CAduringVM test); [2] the CA injection before the VM (CApreVM test). Positive MCA tests were observed in 47 (56%) CAduringVM tests and in 50 (59.5%) CApreVM tests, p=0.64. There was an almost perfect agreement for the positive tests between the CAduringVM and CApreVM test, r s=0.829 (95% CI 0.61-1.00, p<0.001). The present study demonstrates that there is no significant difference in the results of RLS screening by cTCD when two different moments of VM were done.


Towards Convergence: How to Do Transdisciplinary Environmental Health Disparities Research.
Increasingly, funders (i.e., national, public funders, such as the National Institutes of Health and National Science Foundation in the U.S.) and scholars agree that single disciplines are ill equipped to study the pressing social, health, and environmental problems we face alone, particularly environmental exposures, increasing health disparities, and climate change. To better understand these pressing social problems, funders and scholars have advocated for transdisciplinary approaches in order to harness the analytical power of diverse and multiple disciplines to tackle these problems and improve our understanding. However, few studies look into how to conduct such research. To this end, this article provides a review of transdisciplinary science, particularly as it relates to environmental research and public health. To further the field, this article provides in-depth information on how to conduct transdisciplinary research. Using the case of a transdisciplinary, community-based, participatory action, environmental health disparities study in California's Central Valley provides an in-depth look at how to do transdisciplinary research. Working with researchers from the fields of social sciences, public health, biological engineering, and land, air, and water resources, this study aims to answer community residents' questions related to the health disparities they face due to environmental exposure. Through this case study, I articulate not only the logistics of how to conduct transdisciplinary research but also the logics. The implications for transdisciplinary methodologies in health disparity research are further discussed, particularly in the context of team science and convergence science.


Kyphectomy in the treatment of patients with myelomeningocele.
Myelomeningocele kyphosis is a complex disorder that usually requires surgical intervention. Many complications can occur as a result of this disorder and its treatment, but only surgical correction offers the possibility of restoring spinal alignment. The purpose of this retrospective study was to summarize the surgical results, complications, and short-term and midterm outcomes for surgical correction of severe kyphosis using a consistent surgical technique. This was a retrospective review of our database of pediatric patients with myelomeningocele and lumbar kyphosis who underwent kyphectomy with the use of the Warner and Fackler technique. Eleven pediatric kyphectomy cases performed by a single surgeon from 1984 to 2009 were reviewed. Outcome measures include imaging, kyphotic angle measurement, and physical examination. Patients underwent the Warner and Fackler technique of posterior-only kyphectomy and bayonet-shaped anterior sacral fixation. The mean extent of kyphosis was 115.6° (range, 77-176°) preoperatively with a correction to 13.0° (range, 0-32°) postoperatively, and a reduction with an average of 102.6° (range, 65-160°), for an 88.7% correction. On an average, 2.0 (range, 1-6) vertebrae were resected. Immediately postoperatively and at follow-up, with an average of 67.2 months (range, 8-222 months), the average kyphosis angle was 13.0° (range, 0-32°). All patients undergoing the procedure were unable to lie supine preoperatively. All patients postoperatively could lie in the supine position. The functional outcome in patients and caretakers was rated very favorably because all patients and caretakers who provided feedback (9 of 11) reported that they were satisfied with the procedure and would undergo the procedure again if given the choice. This technique has become the most effective surgical reconstruction in myelomeningocele kyphosis. Although significant complications can occur during and after the procedure, most patients had satisfactory postoperative outcomes and restoration of sagittal balance with high patient and parent satisfaction.


Effects of High-Fiber Diets and Macronutrient Substitution on Bloating: Findings From the OmniHeart Trial.
To examine the effects of high-fiber, isocaloric, macronutrient substitutions on bloating. The OmniHeart study is a randomized 3-period crossover feeding trial conducted from April 2003 to June 2005. Participants were provided 3 isocaloric versions of high-fiber (∼30 g per 2,100 kcal) diet, each different in carbohydrate, protein, and unsaturated fat composition. Each feeding period lasted for 6 weeks with a 2- to 4-week washout period between diets. Participants reported the presence and severity of bloating at baseline (participants were eating their own diet) and at the end of each feeding period. One hundred sixty-four participants were included in the analysis (mean age: 53.1 years; 45% women; 55% black). The prevalence of bloating at baseline and at the end of the carbohydrate-rich, protein-rich, and unsaturated fat-rich diet period was 18%, 24%, 33%, and 30%, respectively. Compared with baseline, the relative risk of bloating for the carbohydrate-rich, protein-rich, and unsaturated fat-rich high-fiber diet was 1.34 (95% confidence interval [CI]: 0.93, 1.92), 1.78 (95% CI: 1.32, 2.40), and 1.63 (95% CI: 1.17, 2.26), respectively. The protein-rich diet increased the risk of bloating more than the carbohydrate-rich diet (relative risk = 1.40; 95% CI: 1.03, 1.88). Bloating did not significantly vary between protein-rich vs unsaturated fat-rich or unsaturated fat-rich vs carbohydrate-rich diets. Black participants compared with non-black participants had a higher risk of bloating after all 3 versions of the high-fiber OmniHeart diet (P-value for interaction = 0.012). Substitution of protein with carbohydrate may be an effective strategy to decrease bloating among individuals experiencing gastrointestinal bloating from a high-fiber diet.


Analysis of the roles of FlgP and FlgQ in flagellar motility of Campylobacter jejuni.
Flagellar motility is an important determinant of Campylobacter jejuni that is required for promoting interactions with various hosts to promote gastroenteritis in humans or commensal colonization of many animals. In a previous study, we identified a nonmotile mutant of C. jejuni 81-176 with a transposon insertion in Cj1026c, but verification of the role of the encoded protein in motility was not determined. In this study, we have determined that Cj1026c and the gene immediately downstream, Cj1025c (here annotated as flgP and flgQ, respectively), are both required for motility of C. jejuni but not for flagellar biosynthesis. FlgP and FlgQ are not components of the transcriptional regulatory cascades to activate sigma(28)- or sigma(54)-dependent expression of flagellar genes. In addition, expression of flgP and flgQ is not largely dependent on sigma(28) or sigma(54). Immunblot analyses revealed that the majority of FlgP in C. jejuni is associated with the outer membrane. However, in the absence of FlgQ, the amounts of FlgP in the outer membrane of C. jejuni are greatly reduced, suggesting that FlgQ may be required for localization or stability of FlgP at this location. This study provides insight into features of FlgP and FlgQ, two proteins with previously undefined functions that are required for the larger, multicomponent flagellar system of C. jejuni that is necessary for motility.


The Burden of Binge and Heavy Drinking on the Brain: Effects on Adolescent and Young Adult Neural Structure and Function.
Introduction: Adolescence and young adulthood are periods of continued biological and psychosocial maturation. Thus, there may be deleterious effects of consuming large quantities of alcohol on neural development and associated cognition during this time. The purpose of this mini review is to highlight neuroimaging research that has specifically examined the effects of binge and heavy drinking on adolescent and young adult brain structure and function. Methods: We review cross-sectional and longitudinal studies of young binge and heavy drinkers that have examined brain structure (e.g., gray and white matter volume, cortical thickness, white matter microstructure) and investigated brain response using functional magnetic resonance imaging (fMRI). Results: Binge and heavy-drinking adolescents and young adults have systematically thinner and lower volume in prefrontal cortex and cerebellar regions, and attenuated white matter development. They also show elevated brain activity in fronto-parietal regions during working memory, verbal learning, and inhibitory control tasks. In response to alcohol cues, relative to controls or light-drinking individuals, binge and heavy drinkers show increased neural response mainly in mesocorticolimbic regions, including the striatum, anterior cingulate cortex (ACC), hippocampus, and amygdala. Mixed findings are present in risky decision-making tasks, which could be due to large variation in task design and analysis. Conclusions: These findings suggest altered neural structure and activity in binge and heavy-drinking youth may be related to the neurotoxic effects of consuming alcohol in large quantities during a highly plastic neurodevelopmental period, which could result in neural reorganization, and increased risk for developing an alcohol use disorder (AUD).


Isolation of Providencia heimbachae from human feces.
Providencia heimbachae was first described in 1986. It has been isolated from penguin feces and an aborted bovine fetus. To date, there has been no reported isolation of this organism from human specimens. We now report the isolation of P. heimbachae from the stool of a 23-year-old woman with idiopathic diarrhea. The identity of the human strain was determined biochemically and by DNA relatedness to the type strain of P. heimbachae.


Alaska native mortality rates and trends.
This article compared mortality data (1999-2003) for Alaska Natives (AN), U.S. white residents (USW), and Alaska white residents (AKW), and examined changes in mortality rates from 1979 to 2003. We used SEERStat* software from the National Cancer Institute to calculate age-adjusted mortality rates. The AN all-cause mortality rate was 40% higher (rate ratio [RR]=1.4) than the rate for both the USW and AKW populations. Based on comparisons with USW, the largest disparities in AN mortality were found for unintentional injuries (RR=3.0), suicide (RR=3.1), and homicide (RR=4.4). Disparities were also found for eight of the 10 leading causes of death, including cancer (AN/USW RR=1.3), cerebrovascular disease (RR=1.3), chronic obstructive pulmonary disease (RR=1.4), pneumonia/influenza (RR=1.6), and chronic liver disease (RR=2.0). In contrast, the mortality rate for heart disease among AN was significantly lower (RR=0.9) than for USW, and lower-though not significantly lower-for diabetes. Findings were quite similar when rates for AN were compared with AKW. AKW also had high rates of unintentional injury mortality and suicide compared with USW, but the magnitude of the difference was much less for AKW. From 1979 to 2003, mortality rates among AN declined 16% for all causes, similar to the USW decline of 15%. Monitoring mortality rates and their trends is essential not only to understand the health status of a population but also to target areas for prevention and evaluate the impact of policy change or the effect of interventions over time.


Variations in three-dimensional cancellous bone architecture of the proximal femur in female hip fractures and in controls.
Cubes of cancellous bone were obtained from proximal femora of women with hip fractures (n = 26) and from female cadaveric controls (n = 32) to compare architecture and mechanics between groups. Specimens were scanned on a microcomputed tomography system. Stereologic algorithms and model-based estimates were applied to the data to characterize the three-dimensional cancellous microstructure. Cubes were mechanically tested to failure to obtain mechanical properties. Specimens from control subjects had significantly higher bone volume fraction, trabecular number, and connectivity than specimens from patients with hip fractures; no difference in trabecular thickness was observed between groups. Both maximum modulus and ultimate stress were significantly higher in the control than in the fracture group, consistent with the higher bone volume found in the control group. No statistical differences in any of these architectural or mechanical variables were found when groups were matched for bone volume. Specimens from both patients with hip fractures and controls demonstrated strong relationships between trabecular number and bone volume fraction that were statistically equivalent, suggesting that for a given bone mass, both groups have the same overall number of trabeculae. However, there was an architectural difference between fracture and control groups in terms of the three-dimensional spatial arrangement of trabeculae. Fracture specimens had a significantly more anisotropic (oriented) structure than control specimens, with proportionately fewer trabecular elements transverse to the primary load axis, even when matched for bone volume. Relationships between mechanical and architectural parameters were significantly different between groups, suggesting that fracture and control groups have different structure-mechanics relationships, which we hypothesize may be a consequence of the altered three-dimensional structure between groups.


Toxicity of muscimol and ibotenic acid containing mushrooms reported to a regional poison control center from 2002-2016.
Amanita muscaria (AM) and A. pantherina (AP) contain ibotenic acid and muscimol and may cause both excitatory and sedating symptoms. Gastrointestinal (GI) symptoms are not classically described but have been reported. There are relatively few reported cases of poisoning with these mushrooms in North America. This is a retrospective review of ingestions of ibotenic acid and muscimol containing mushrooms reported to a United States regional poison center from 2002-2016. Cases were included if identification was made by a mycologist or if AM was clearly described. Thirty-four cases met inclusion criteria. There were 23 cases of AM, 10 AP, and 1 A. aprica. Reason for ingestion included foraging (12), recreational (6), accidental (12), therapeutic (1), self-harm (1), and unknown (2). Of the accidental pediatric ingestions 4 (25%) were symptomatic. None of the children with a symptomatic ingestion of AM required admission. A 3-year-old male who ingested AP had vomiting, agitation, and lethargy and received benzodiazepines. He was intubated and had a 3-day ICU stay. There were 25 symptomatic patients. All but one patient developed symptoms within 6 h. Six patients had symptoms for less than 6 h while 15 had symptoms lasting less than 24 h. Ingestions of AP were more symptomatic than AM with regard to the presence of any GI symptoms (80% vs. 35%), central nervous system (CNS) depression (70% vs. 35%), and CNS excitation (70% vs. 35%) respectively. Five patients were intubated. No patients experienced hypotension, seizures, acute kidney injury, or hepatotoxicity. No deaths were reported. Ingestion of ibotenic acid/muscimol containing mushrooms often produces a syndrome with GI upset, CNS excitation, and CNS depression either alone or in combination. Ingestion of AP was associated with a higher rate of symptoms compared to AM.


Anticancer and anti-inflammatory activities of shallot (Allium ascalonicum) extract.
Alliumplants are an important part of the diet of many populations and there is a long-held belief in their health-enhancing properties such as cancer prevention. In this study, the anticancer and anti-inflammatory activities of the aqueous extract of the Allium ascalonicum bulbs have been studied. The antiproliferative and anti-growth activity of the aqueous extract of A. ascalonicum was examined in vitro on different tumor cell lines. Furthermore, the acetic acid-induced vascular permeability as an in vivo assay was used for studying anti-inflammatory activity of the extract. The aqueous extract of A. ascalonicum had the most anti-growth activity on the cancer cell lines; Jurkat and K562 against Wehi 164 with lower cytotoxic preference. The extract also showed much less cytotoxicity against the normal cell (HUVEC) line and significant anti-inflammatory activity in vivo. It is of interest that the extract of this plant has shown much less cytotoxicity against the normal cell line, and, if this also occurs in vivo, the use of this plant clinically for the treatment of cancer patients would have some scientific support. The results of these assays indicated that A. ascalonicum can be a candidate for prevention and treatment of many diseases related to inflammation and malignancy.


Melatonin administration enhances the reproductive capacity of young rams under a southern Mediterranean environment.
This study tested the effect of melatonin treatment, initiated in late February on reproductive traits of young rams. A total of 14 young Barbarine rams were used. Seven animals were treated with three melatonin subcutaneous implants (Melatonin) on 28 February while the remaining rams remained untreated (Control). After 60 days of melatonin administration, scrotal circumference reached average values of 32.1 ± 1.54 and 29.5 ± 1.0 cm for Melatonin and Control animals, respectively (P < 0.05). Semen characteristics did not differ between groups; melatonin treatment tended (P = 0.091) to increase sperm concentration 60 days after implantation when means reached 5.87 ± 0.703 and 4.61 ± 0.654 × 10(9) spermatozoa/mL for Melatonin and Control rams, respectively. Melatonin treatment significantly affected total activity time, number of lateral approaches and mount attempts in comparison to controls. During a 6-h sampling period, mean plasma testosterone concentrations increased as a result of melatonin treatment (P < 0.001) and testosterone pulse frequency averaged 3.45 ± 2.24 and 1.25 ± 1.0 (P = 0.086) for Melatonin and Control rams. Data clearly suggest that abrupt treatment of young rams with melatonin implants in winter is sufficient to improve reproductive traits.


The oral contraceptive pill: a revolution for sportswomen?
To determine the effects of the oral contraceptive pill (OCP) on skeletal health, soft tissue injury, and performance in female athletes. A literature review was performed using literature retrieval methods to locate relevant studies. Most female athletes primarily choose to use the OCP for contraceptive purposes, but cycle manipulation and control of premenstrual symptoms are secondary advantages of its use. The effect of the OCP on bone density in normally menstruating women is unclear, with some studies reporting no effect, others a positive effect, and some even a negative effect. The OCP is often prescribed for the treatment of menstrual disturbances in female athletes, and improvements in bone density may result. Whether the OCP influences the risk of stress fracture and soft tissue injuries is not clear from research to date. Effects of the OCP on performance are particularly relevant for elite sportswomen. Although a reduction in Vo2MAX has been reported in some studies, this may not necessarily translate to impaired performance in the field. Moreover, some studies claim that the OCP may well enhance performance by reducing premenstrual symptoms and menstrual blood loss. A fear of weight gain with the use of the OCP is not well founded, as population studies report no effect on weight, particularly with the lower dose pills currently available. Overall, the advantages of the pill for sportswomen would appear to outweigh any potential disadvantages. Nevertheless, there is individual variation in response to the OCP and these should be taken into account and monitored in the clinical situation. Women should be counselled as to the range of potential benefits and disadvantages in order to make an informed decision based on individual circumstances.


Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer.
Despite its widespread use, the use of prostate-specific antigen (PSA) alone as a screening biomarker for prostate cancer (PCa) leads often to unwarranted prostate biopsy, over-diagnosis, and consequently, over-treatment, because of its limited specificity. There are reports that the apoptosis inhibitor of macrophage (AIM), secreted mainly by macrophages and epithelial cells, is upregulated during inflammation and facilitates immune recognition of cancerous cells by blocking human regulator of complement activation. These controversies around the PSA utility necessitate a reexamination of its use as a screening tool. More so, despite the suggested implication of AIM in anticancer immunosurveillance, there is a dearth of information on its role in therapy response, disease progression, and clinical outcomes of patients with PCa. These inform the present study to probe the nature and role of AIM/PSA signaling in anticancer immunity and prognosis in PCa. A combination of bioinformatics-aided statistical analyses, gene function annotation, and immune infiltrate analyses, coupled with tissue staining, and function assays, namely migration, invasion, and clonogenicity assays, we employed. We demonstrated that AIM and PSA expression levels are inversely correlated in PCa clinical samples and cell lines, with AIMlowPSAhigh defining PCa, compared to AIMhighPSAlow in normal samples. Concomitant aberrant PSA and significantly suppressed AIM expression levels positively correlated with high-grade disease and characterized by advanced stage prostate cancer, regardless of mutation status. We found that a high PSA/AIM ratio is associated with disease recurrence in patients with prostate cancer but is equivocal for overall survival. In addition, PSA-associated AIM suppression is implicated in the enhanced 'metastability' of PCa and a high AIM/PSA ratio is associated with strong castration-induced regression. CRISPR-mediated AIM knockout was associated with higher PSA expression while ectopic expression of AIM significantly attenuated the migration and invasive capability of PC3 and DU145 cells. Interestingly, compared to normal samples, we observed that AIM, biomarkers of T-cell activation and M1 phenotype markers are co-suppressed in PCa samples. Herein, we demonstrate that AIM/CD5L binds to PSA and that a high PSA/AIM ratio defines advanced stage PCa (regardless of mutation status), is implicated in enhanced metastability, and associated with disease recurrence, while a high AIM/PSA ratio is associated with strong castration-induced regression. More so, the ectopic expression of AIM significantly enhances the anticancer effect of Pembrolizumab and elicits an increased CD8+ T-cell count in AIMhiPSAloPDL1+ PCa cases that are respondent to Pembrolizumab treatment.


Exploring care transitions from patient, caregiver, and health-care provider perspectives.
Care transitions involve coordination of patient care across multiple care settings. Many problems occur during care transitions resulting in negative patient outcomes and unnecessary readmissions. The purpose of this study was to describe the experience of care transitions from patient, caregiver, and health-care provider perspectives in a single metropolitan Midwest city. A qualitative descriptive design was used to solicit patients', caregivers', and health-care providers' perceptions of care transitions, their role within the process, barriers to effective care transitions, and strategies to overcome these barriers. Five themes emerged: preplanned admissions are ideal; lack of needed patient information upon admission; multiple services are needed in preparing patients for discharge; rushed or delayed discharges lead to patient misunderstanding; and difficulties in following aftercare instructions. Findings illustrated provider difficulty in meeting multiple care needs, and the need for patient-centered care to achieve positive outcomes associated with quality measures, reduced readmissions, and care transitions.


Development of a high-throughput method for the systematic identification of human proteins nuclear translocation potential.
Important clues to the function of novel and uncharacterized proteins can be obtained by identifying their ability to translocate in the nucleus. In addition, a comprehensive definition of the nuclear proteome undoubtedly represents a key step toward a better understanding of the biology of this organelle. Although several high-throughput experimental methods have been developed to explore the sub-cellular localization of proteins, these methods tend to focus on the predominant localizations of gene products and may fail to provide a complete catalog of proteins that are able to transiently locate into the nucleus. We have developed a method for examining the nuclear localization potential of human gene products at the proteome scale by adapting a mammalian two-hybrid system we have previously developed. Our system is composed of three constructs co-transfected into a mammalian cell line. First, it contains a PCR construct encoding a fusion protein composed of a tested protein, the PDZ-protein TIP-1, and the transactivation domain of TNNC2 (referred to as ACT construct). Second, our system contains a PCR construct encoding a fusion protein composed of the DNA binding domain of GAL4 and the PDZ binding domain of rhotekin (referred to as the BIND construct). Third, a GAL4-responsive luciferase reporter is used to detect the reconstitution of a transcriptionally active BIND-ACT complex through the interaction of TIP-1 and rhotekin, which indicates the ability of the tested protein to translocate into the nucleus. We validated our method in a small-scale feasibility study by comparing it to green fluorescent protein (GFP) fusion-based sub-cellular localization assays, sequence-based computational prediction of protein sub-cellular localization, and current sub-cellular localization data available from the literature for 22 gene products. Our reporter-based system can rapidly screen gene products for their ability to be translocated to the nucleus. Large-scale applications of the system presented herein should provide invaluable information for a more complete biological atlas.


Optical characteristics of silver-doped polarizing glass.
According to the theory of scattering and absorption of light, an anisotropic Ag colloid particle, which is small compared with the wavelength of the incident light, absorbs light differently in different directions. The underlying mechanism is regarded as electron plasma resonance. The optical anisotropy of a single Ag particle or of a group of the same particles has been analyzed. An equation for estimating the distribution of the particle shapes in space is proposed. Based on this equation and the work of other researchers, a program was designed to calculate the major principal transmittance and the minor principal transmittance of Ag-doped polarizing glass. The results show that the polarizing property of glass with particles with different aspect ratios is better than that of glass with identical particles. Also, the effective wavelength range is different if the particles' aspect ratios change, and this range tends to narrow as the parameter R (the rate of change of the aspect ratio) is increased.


Impact of open-access scheduling on realized access.
Open-access or advanced-access scheduling, which opens the clinic calendar to patients without requiring them to schedule far in advance of the visit, is being introduced in primary care for the purpose of improving access. None of the evaluations reported to date have measured differences in actual visits that might be associated with different scheduling systems. The purpose of this study was to compare utilization of visits to primary care providers for patients served by an open-access clinic with utilization patterns of patients served at clinics not using open-access scheduling. We hypothesized that the odds that a continuing patient received more than one primary care visit would be greater in the clinic where open-access scheduling was in use than in comparison clinics. Our study provides mixed support for the hypotheses. After adjustment for case mix, stable chronic patients treated in open-access clinics may sometimes have greater odds of receiving two or more preventive care visits. However, these effects do not occur in all clinics, suggesting that other clinic characteristics may overcome the effects of open-access scheduling.


Haematologic features of the human immunodeficiency virus (HIV) infection in Black children in Harare.
Forty six Black Zimbabwean children aged between three months and seven years who were admitted into Parirenyatwa Central Hospital with serologically positive and symptomatic HIV infection were investigated for their haematologic profiles. Tests done included full blood counts, manual white cell differential counts, coagulation screening tests and bone marrow aspiration in clinically indicated cases. Anaemia was found in 84 pc, leucocytosis in 60 pc and thrombocytopaenia in 30 pc of the cases. In contrast to reports in adults leucopaenia or neutropaenia were not seen. Coagulation profiles were mostly normal but presumptive diagnosis of circulating coagulation inhibitor was made in one case. Morphological changes suggestive of myeloid dysplasia and in particular dysgranulopoiesis were commonly seen. Bone marrow aspirates examined in eight of the children all showed hyper or normal cellularity with adequate and productive megakaryocytes.


Distinct patterns of hybridization across a suture zone in a coral reef fish (Dascyllus trimaculatus).
Hybrid zones are natural laboratories for investigating the dynamics of gene flow, reproductive isolation, and speciation. A predominant marine hybrid (or suture) zone encompasses Christmas Island (CHR) and Cocos (Keeling) Islands (CKE), where 15 different instances of interbreeding between closely related species from Indian and Pacific Oceans have been documented. Here, we report a case of hybridization between genetically differentiated Pacific and Indian Ocean lineages of the three-spot dascyllus, Dascyllus trimaculatus (Rüppell, 1829). Field observations indicate there are subtle color differences between Pacific and Indian Ocean lineages. Most importantly, population densities of color morphs and genetic analyses (mitochondrial DNA and SNPs obtained via RADSeq) suggest that the pattern of hybridization within the suture zone is not homogeneous. At CHR, both color morphs were present, mitochondrial haplotypes of both lineages were observed, and SNP analyses revealed both pure and hybrid genotypes. Meanwhile, in CKE, the Indian Ocean color morphs were prevalent, only Indian Ocean mitochondrial haplotypes were observed, and SNP analysis showed hybrid individuals with a large proportion (~80%) of their genotypes assigning to the Indian Ocean lineage. We conclude that CHR populations are currently receiving an influx of individuals from both ocean basins, with a greater influence from the Pacific Ocean. In contrast, geographically isolated CKE populations appear to be self-recruiting and with more influx of individuals from the Indian Ocean. Our research highlights how patterns of hybridization can be different at scales of hundreds of kilometers, due to geographic isolation and the history of interbreeding between lineages.


Quantification of epithelial cell proliferation, cell dynamics, and cell kinetics in vivo.
The measurement of cell proliferation in vivo is usually carried out by the examination of static measures. These comprise the mitotic index or labeling indices using incorporation of DNA synthesis markers such as bromodeoxyuridine or tritiated thymidine, or intrinsic markers, such as Ki67 and proliferative cell nuclear antigen (PCNA). But static measures only provide a 'snapshot' of cell proliferation. Rate measures, including double labeling methods and the metaphase arrest method, can actually measure cell production rates but they are far less utilized at present. Transit times and migration rates can also be measured using pulse and chase labeling or by following the transit of labeled cells through the tissue. Simple indices of cell division can easily be confounded by concomitant changes in the compartment size and many alleged markers of proliferation have serious shortcomings, as the markers may be involved in multiple aspects of cell regulation. The complexities of studying proliferation in vivo are illustrated here with a focus on the gastrointestinal tract. Some of these methods can help elucidate the role of the stem cells and their relationship to label retaining cells. WIREs Dev Biol 2017, 6:e274. doi: 10.1002/wdev.274 For further resources related to this article, please visit the WIREs website.


Relative importance of photosynthetic traits and allocation patterns as correlates of seedling shade tolerance of 13 tropical trees.
Among 13 tropical tree species on Barro Colorado Island, species with high seedling mortality rates during the first year in shade had higher reltive growth rates (RGR) from germination to 2 months in both sun (23% full sun) and shade [2%, with and without lowered red: far red (R:FR) ratio] than shade tolerant species. Species with higher RGR in sun also had higher RGR in shade. These interspecific trends could be explained by differences in morphological traits and allocation paterns among species. Within each light regime, seedlings of shade-intolerant species had lower root: shoot ratios, higher leaf mass per unit area, and higher leaf area ratios (LAR) than shade tolerant species. In contrast, leaf gas exchange characteristics, or acclimation potential in these traits, had no relationship with seedling mortality rates in shade. In both shade tolerant and intolerant species, light saturated photosynthesis rates, dark respiration, and light compensation points were higher for sungrown seedlings than for shade-grown seedlings. Differences in R:FR ratio in shade did not affect gas exchange, allocation patterns, or growth rates of any species. Survival of young tree seedlings in shade did not depend on higher net photosynthesis or biomass accumulation rates in shade. Rather, species with higher RGR died faster in shade than species with lower RGR. This trend could be explained if survival depends on morphological characteristics likely to enhance defense against herbivores and pathogens, such as dense and tough leaves, a well-established root system, and high wood density. High construction costs for these traits, and low LAR as a consequence of these traits, should result in lower rates of whole-plant carbon gain and RGR for shade tolerant species than shade-intolerant species in shade as well as in sun.


Simulants of Malignant Melanoma.
During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN) of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential) and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential). In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM) variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas), and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.


Activation of the heat shock response in a primary cellular model of motoneuron neurodegeneration-evidence for neuroprotective and neurotoxic effects.
Pharmacological up-regulation of heat shock proteins (hsps) rescues motoneurons from cell death in a mouse model of amyotrophic lateral sclerosis. However, the relationship between increased hsp expression and neuronal survival is not straightforward. Here we examined the effects of two pharmacological agents that induce the heat shock response via activation of HSF-1, on stressed primary motoneurons in culture. Although both arimoclomol and celastrol induced the expression of Hsp70, their effects on primary motoneurons in culture were significantly different. Whereas arimoclomol had survival-promoting effects, rescuing motoneurons from staurosporin and H(2)O(2) induced apoptosis, celastrol not only failed to protect stressed motoneurons from apoptosis under same experimental conditions, but was neurotoxic and induced neuronal death. Immunostaining of celastrol-treated cultures for hsp70 and activated caspase-3 revealed that celastrol treatment activates both the heat shock response and the apoptotic cell death cascade. These results indicate that not all agents that activate the heat shock response will necessarily be neuroprotective.


Modeling the phase behavior in mixtures of pharmaceuticals with liquid or supercritical solvents.
The concept of solubility parameter, which is widely used for the screening of solvents in pharmaceutical applications, is combined with a thermodynamic theory that is able to model systems with large deviations from ideal behavior. The nonrandom hydrogen-bonding (NRHB) theory is applied to model the phase behavior of mixtures of six pharmaceuticals (i.e., ibuprofen, ketoprofen, naproxen, benzoic acid, methyl paraben, and ethyl paraben). The pure fluid parameters of the studied pharmaceuticals were estimated using limited available experimental (or predicted) data on sublimation pressures, liquid densities, and Hansen's solubility parameters. The complex hydrogen-bonding behavior was explicitly accounted for, while the corresponding parameters were adopted from simpler molecules of similar chemical structure or/and fitted to the aforementioned pure fluid properties. In this way, the solubility of the studied pharmaceuticals in liquid solvents was calculated. The average root-mean-square deviation between experimental and calculated solubilities is 0.190 and 0.037 in log(10) units for prediction (calculations without a binary interaction parameter adjustment) and for correlation (calculations using one binary interaction parameter fitted to experimental data), respectively. In addition, using one temperature-independent binary interaction parameter the phase behavior of pharmaceuticals in supercritical CO(2) and ethane was satisfactorily correlated. Finally, preliminary encouraging results are shown concerning two ternary mixtures where the model is able to predict accurately the solubility of pharmaceuticals in mixed solvents based on interaction parameters fitted to corresponding single solvent data.


German Health Update: New data for Germany and Europe: The background to and methodology applied in GEDA 2014/2015-EHIS.
GEDA 2014/2015-EHIS is an up-to-date health survey of the adult population undertaken within the framework of the Robert Koch Institute's (RKI) health monitoring system. It uses the EHIS (European Health Interview Survey) Wave 2 questionnaire and includes four modules covering health status, health care, health determinants, and socio-economic variables. Data on nationally relevant issues is also collected. The study employs a mixed-mode design, using both online and paper-based questionnaires to gather data from 24,016 people aged 18 and above: the response rate was 26.9%. The Statistical Office of the European Union (Eurostat) provides prepared data from 28 European Union (EU) member states (plus Norway and Iceland) on the Eurostat website. National analyses for Germany are published as Fact sheets on health reporting in the Journal of Health Monitoring.


Differential outcomes enhance accuracy of delayed matching to sample but not resistance to change.
Three experiments assessed the relation between the differential outcomes effect and resistance to change of delayed matching-to-sample performance. Pigeons produced delayed matching-to-sample trials by responding on variable interval schedules in two components of a multiple schedule. In the same-outcome component, the probability of reinforcement was the same for both samples (.9 in Experiments 1 and 2, .5 in Experiment 3); in the different-outcomes component, the probability of reinforcement was .9 for one sample and .1 for the other. In all three experiments, the forgetting functions in the different-outcomes component were higher and shallower than in the same-outcomes component. When total reinforcement was greater in the same-outcomes component (Experiments 1 and 2), resistance to disruption by prefeeding, intercomponent food, extinction, or flashing lights typically was greater in that component. In Experiment 3, when total reinforcement was equated, resistance to disruption was similar across components. Thus, the level and slope of forgetting functions depended on differential reinforcement correlated with the samples, but the resistance to change of forgetting functions depended on total reinforcement in a component. Both aspects of the results can be explained by a model of delayed matching to sample performance.


Randomized trial of targeted performance feedback to facilitate quality improvement in acute myocardial infarction care.
Efforts to improve quality of care for patients with acute myocardial infarction (AMI) are a national priority. To date, there have been few studies that have prospectively evaluated hospital quality improvement (QI) interventions. Using hospitals in the National Cardiovascular Data Registry (NCDR) ACTION Registry-GWTG, a cluster randomized trial of the effectiveness of targeted performance feedback to facilitate process improvement for AMI care will be conducted. ACTION Registry-GWTG hospitals with a minimum of 50 AMI patients per 2 quarters are eligible for randomization. The control arm receives standard performance feedback reports, and the intervention arm receives standard performance feedback reports in addition to a supplemental report on the "top 3" centrally identified, hospital-specific performance gaps. The primary outcome will be improvement in a composite of all metrics, and the secondary outcome will be improvement in the targeted metrics. At study inception in January 2009, 149 sites were randomized: 76 to the intervention arm, and 73 to the control arm. Intervention and control sites were well balanced in terms of baseline performance, center characteristics, and AMI volume (≈70 patients per quarter). The intervention phase will continue for 5 feedback cycles, each containing 2 quarters of data feedback over 18 months. A final trial outcome report will follow. This randomized trial will evaluate a novel hospital-level QI intervention of targeted performance feedback for AMI, thereby demonstrating the effective use of national registries for QI and furthering our understanding of effective QI methods.


Glutamate receptor-channel gating. Maximum likelihood analysis of gigaohm seal recordings from locust muscle.
Gigaohm recordings have been made from glutamate receptor channels in excised, outside-out patches of collagenase-treated locust muscle membrane. The channels in the excised patches exhibit the kinetic state switching first seen in megaohm recordings from intact muscle fibers. Analysis of channel dwell time distributions reveals that the gating mechanism contains at least four open states and at least four closed states. Dwell time autocorrelation function analysis shows that there are at least three gateways linking the open states of the channel with the closed states. A maximum likelihood procedure has been used to fit six different gating models to the single channel data. Of these models, a cooperative model yields the best fit, and accurately predicts most features of the observed channel gating kinetics.


Rates of glutathione synthesis in lung subcompartments of mice and monkeys: possible role in species and site selective injury.
Injury to pulmonary epithelial cells from chemicals that undergo P450-dependent metabolic activation and from gases such as ozone is highly focal. These studies examined the rates of glutathione resynthesis in pulmonary subcompartments (trachea, minor daughter/respiratory bronchiole and parenchyma) of mice and monkeys to determine whether differences in glutathione synthesis are partly responsible for wide regional/species variations in susceptibility of the lung to insult. Glutathione levels remained unchanged in lung subcompartments incubated for up to 4 hr in Waymouth's medium. Glutathione levels decreased less than 30% in 4-hr incubations of monkey airways in medium devoid of sulfur amino acids although in mouse airways decreases of 40 to 60% were observed. Diethyl maleate depleted glutathione in lung subcompartments in vitro by varying amounts depending on the species and subcompartment examined. Airways incubated in the presence of cysteine but not methionine or glutathione regenerated glutathione rapidly after diethyl maleate depletion. The rates of regeneration differed significantly with species and airway level. In all airways of the monkey, glutathione levels returned to the initial level within 2 to 4 hr after addition of cysteine containing medium although in mice recovery of glutathione required only 1 (minor daughter and parenchyma) or 2 hr (trachea) incubation with cysteine supplemented medium. These studies show striking species and airway level differences in the rates of glutathione resynthesis and suggest that focal injury to respiratory epithelium may, in part, be mediated by regional differences in the ability to supply glutathione for protection against electrophiles and reactive oxygen species.


Descriptive profile of the academic integrity of Australian occupational therapy students.
Academic integrity is the moral code of academia. Students who demonstrate trustworthiness in an academic setting are more likely to be dependable in a clinical setting. It is, therefore, important for occupational therapy academic and fieldwork educators to know the academic integrity profile of their students and to address any areas of academic dishonesty in curriculum design and delivery. To date, there has been no baseline description of the academic honesty profile of Australian occupational therapy students. To establish a baseline of academic integrity and academic dishonesty among occupational therapy undergraduate and graduate-entry masters students in a cohort of Australian students. Seven hundred and one students from five Australian universities completed a self-report questionnaire comprising demographic questions and six standardised scales measuring academic integrity. Overall, occupational therapy students reported high levels of academic and fieldwork integrity; however, some areas of concerns exist. Students report copying material without citations at least once during their studies (55%), obtaining test questions at least once during their studies (42.6%) or padding out a bibliography (39.5%). Occupational therapy education needs to continue to emphasise the importance of academic and fieldwork integrity. Students need to be explicitly taught what academic honesty and dishonesty is and be provided with the resources and time to complete academic work to reduce the risk of academic dishonesty.


Effect of methionine loading on 5-methyltetrahydrofolate, S-adenosylmethionine and S-adenosylhomocysteine in plasma of healthy humans.
1. Elevated plasma homocysteine concentration, either in the fasting state or after methionine loading, is an independent risk factor for vascular disease in man. Methionine loading has been used to investigate impaired methionine metabolism, especially of the trans-sulphuration pathway, but most studies have focused on changes in homocysteine. 2. We investigated the effect of methionine excess on total plasma homocysteine, 5-methyltetrahydrofolate (which is the active form of folate in the remethylation of homocysteine to methionine), S-adenosyl-methionine (the first metabolite of methionine) and S-adenosylmethionine) (the demethylated product of S-adenosylmethionine) over 24h in 12 healthy subjects. 3. As well as the expected increase in homocysteine (from 8.0 +/- 1.3 to 32.6 +/- 10.3 mumol/l, mean +/- SD, P < 0.001), S-adenosylmethionine showed a significant transient increase (from 37.9 +/- 25.0 to 240.3 +/- 109.2 nmol/l, P < 0.001), which correlated well with homocysteine (r2 = 0.92, P < 0.001). 5-Methyltetrahydrofolate values decreased significantly (from 23.2 +/- 7.2 to 13.1 +/- 2.9 nmol/l, P < 0.01), and gradually returned to baseline levels after 24h. No significant change over the time of measurement was found for S-adenosylhomocysteine. 4. The sequence of metabolic changes observed in this study strongly suggests that a change in either homocysteine or S-adenosylmethionine may cause a reduction in 5-methyltetrahydrofolate. This must be considered in evaluating the relationship between folate and homocysteine in vascular disease. The metabolic relationships illustrated in this study should be evaluated in the search for pathogenetic mechanisms of mild hyperhomocysteinaemia and vascular disease.


Genetic mapping of SrCad and SNP marker development for marker-assisted selection of Ug99 stem rust resistance in wheat.
New SNP markers that can be used for marker-assisted selection and map-based cloning saturate the chromosome region carrying SrCad , a wheat gene that confers resistance to Ug99 stem rust. Wheat stem rust, caused by Puccinia graminis f. sp. tritici, is a devastating disease of wheat worldwide. Development of cultivars with effective resistance has been the primary means to control this disease, but the appearance of new virulent strains such as Ug99 has rendered most wheat varieties vulnerable. The stem rust resistance gene SrCad located on chromosome arm 6DS has provided excellent resistance to various strains of Ug99 in field nurseries conducted in Njoro, Kenya since 2005. Three genetic populations were used to identify SNP markers closely linked to the SrCad locus. Of 220 SNP markers evaluated, 27 were found to be located within a 2 cM region surrounding SrCad. The diagnostic potential of these SNPs was evaluated in a diverse set of 50 wheat lines that were primarily of Canadian origin with known presence or absence of SrCad. Three SNP markers tightly linked proximally to SrCad and one SNP that co-segregated with SrCad were completely predictive of the presence or absence of SrCad. These markers also differentiated SrCad from Sr42 and SrTmp which are also located in the same region of chromosome arm 6DS. These markers should be useful in marker-assisted breeding to develop new wheat varieties containing SrCad-based resistance to Ug99 stem rust.


DNA polymerase betas from liver and testes of cherry salmon, Oncorhynchus masou: purification and characterization of DNA polymerase betas with acidic isoelectric points.
DNA polymerase betas from cherry salmon, Oncorhynchus masou, liver and testes were purified to near homogeneity, and no substantial differences between the enzymes were observed. The molecular weight of both enzymes, determined by SDS-polyacrylamide gel electrophoresis, was 39,000. The amino acid sequences of the N-terminus of the liver and testes enzymes were determined and compared with that of the rat enzyme. Of the N-terminal 30 amino acid residues of salmon liver DNA polymerase beta, 21 (70%) were identical to those of the rat enzyme sequence. However, unlike most eukaryotic DNA polymerase betas, the isoelectric points (pIs) of the DNA polymerase betas from salmon liver and testes were both estimated to be 6.2, which is significantly different from the alkaline isoelectric points (pI = 8.5-9.5) established for other highly purified vertebrate DNA polymerase betas. The cherry salmon DNA polymerase betas were still active at below 10 degrees C, compared with the rat enzyme.


Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical library.
For patients with solid tumors, the tolerance of surrounding tissues often limits the dose of radiation that can be delivered. Thus, agents that preferentially increase the cytotoxic effects of radiation toward tumor cells would significantly alter the therapeutic ratio and improve patient survival. Using a high-throughput, unbiased screening approach, we have identified 4'-bromo-3'-nitropropiophenone (NS-123) as a radiosensitizer of human glioma cells in vitro and in vivo. NS-123 radiosensitized U251 glioma cells in a dose-dependent and time-dependent manner, with dose enhancement ratios ranging from 1.3 to 2.0. HT-29 colorectal carcinoma and A549 lung adenocarcinoma cells were also radiosensitized by NS-123 in vitro, whereas NS-123 did not increase the radiation sensitivity of normal human astrocytes or developmental abnormalities or lethality of irradiated Zebrafish embryos. In a novel xenograft model of U251 cells implanted into Zebrafish embryos, NS-123 enhanced the tumor growth-inhibitory effects of ionizing radiation (IR) with no apparent effect on embryo development. Similar results were obtained using a mouse tumor xenograft model in which NS-123 sensitized U251 tumors to IR while exhibiting no overt toxicity. In vitro pretreatment with NS-123 resulted in accumulation of unrepaired IR-induced DNA strand breaks and prolonged phosphorylation of the surrogate markers of DNA damage H2AX, ataxia telangiectasia mutated protein, DNA-dependent protein kinase, and CHK2 after IR, suggesting that NS-123 inhibits a critical step in the DNA repair pathway. These results show the potential of this cell-based, high-throughput screening method to identify novel radiosensitizers and suggest that NS-123 and similar nitrophenol compounds may be effective in antiglioma modalities.


Does school mobility place elementary school children at risk for lower math achievement? The mediating role of cognitive dysregulation.
Children growing up in poverty have a higher likelihood of exposure to multiple forms of adversity that jeopardize their chances of academic success. The current paper identifies school mobility, or changing schools, as 1 such poverty-related risk. Using a sample of low-income, predominantly ethnic-minority children (n = 381) in Chicago, this study tests the hypothesis that repeatedly changing schools during the 5-year period between Head Start (preschool) and third grade is a potent predictor of children's math achievement in fourth grade and that children's cognitive dysregulation serves as a mechanism through which school mobility may negatively affect children's math achievement. Hierarchical linear models controlling for baseline child and family characteristics (including children's early math and dysregulation measured during Head Start) revealed an inverse relation between the number of times low-income children changed schools between preschool and third grade and children's math achievement on state standardized tests in fourth grade. Furthermore, frequently changing schools (3 or 4 school changes over the same time period) was positively associated with teacher-reported cognitive dysregulation in third grade and negatively associated with children's math achievement in fourth grade. Evidence for the role of children's cognitive dysregulation as a partial statistical mediator was found for the relation between frequently changing schools and math achievement, even after accounting for baseline risk. Results are discussed in terms of school policies, practices, and intervention strategies to prevent the disruptive and potentially stressful experiences of school mobility for young, low-income children.


Metallically confined microdisks with in-plane multiple guided emissions.
We theoretically present in-plane multiple guided emissions of metallically confined microdisk lasers which can be applied to drive multiple elements in compact photonic integration at the same time. Two to four-port microdisks with transverse magnetic and electric polarizations are investigated based on finite difference time domain simulation and padé approximation. Modes filtering of coupling ports are verified by the calculated mode quality factors (Q) which are decided by the matching of coupling ports with the energy density distribution of corresponding modes. Single mode lasing operation of semiconductor microdisk with guided emissions is possibly realized by selectively pumping.


Using GIS and perceived distance to understand the unequal geographies of healthcare in lower-income urban neighbourhoods.
Geographers play important roles in public health research, particularly in understanding healthcare accessibility, utilisation, and individual healthcare experiences. Most accessibility studies have benefited from the increased sophistication of geographic information systems (GIS). Some studies have been enhanced with semi-structured in-depth interviews to understand individual experiences of people as they access healthcare. However, few accessibility studies have explicitly utilised individual in-depth interview data in the construction of new GIS accessibility measures. Using mixed methods including GIS analysis and individual data from semi-structured in-depth interviews, we offer satisfaction-adjusted distance as a new way of conceptualising accessibility in GIS. Based on fieldwork in a predominantly lower-income community in Columbus, Ohio (USA), we find many residents felt neighbourhood healthcare facilities offered low-quality care, which suggested an added perceived distance as they attempt to access high-quality healthcare facilities. The satisfaction-adjusted distance measure accounts for the perceived distance some residents feel as they search for high-quality healthcare in lower-income urban neighbourhoods. In moving beyond conventional GIS and re-conceptualising accessibility in this way, we offer a more realistic portrayal of the issues lower-income urban residents face as they attempt to access high-quality healthcare facilities. The work has theoretical implications for conceptualising healthcare accessibility, advances the mixed-methodologies literature, and argues for a more equitable distribution of high-quality healthcare in urban neighbourhoods.


Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds.
Although extensive data exist on avian influenza in wild birds in North America, limited information is available from elsewhere, including Europe. Here, molecular diagnostic tools were employed for high-throughput surveillance of migratory birds, as an alternative to classical labor-intensive methods of virus isolation in eggs. This study included 36,809 samples from 323 bird species belonging to 18 orders, of which only 25 species of three orders were positive for influenza A virus. Information on species, locations, and timing is provided for all samples tested. Seven previously unknown host species for avian influenza virus were identified: barnacle goose, bean goose, brent goose, pink-footed goose, bewick's swan, common gull, and guillemot. Dabbling ducks were more frequently infected than other ducks and Anseriformes; this distinction was probably related to bird behavior rather than population sizes. Waders did not appear to play a role in the epidemiology of avian influenza in Europe, in contrast to the Americas. The high virus prevalence in ducks in Europe in spring as compared with North America could explain the differences in virus-host ecology between these continents. Most influenza A virus subtypes were detected in ducks, but H13 and H16 subtypes were detected primarily in gulls. Viruses of subtype H6 were more promiscuous in host range than other subtypes. Temporal and spatial variation in influenza virus prevalence in wild birds was observed, with influenza A virus prevalence varying by sampling location; this is probably related to migration patterns from northeast to southwest and a higher prevalence farther north along the flyways. We discuss the ecology and epidemiology of avian influenza A virus in wild birds in relation to host ecology and compare our results with published studies. These data are useful for designing new surveillance programs and are particularly relevant due to increased interest in avian influenza in wild birds.


Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes.
To evaluate the association between cumulative duration of metformin use after prostate cancer (PC) diagnosis and all-cause and PC-specific mortality among patients with diabetes. We used a population-based retrospective cohort design. Data were obtained from several Ontario health care administrative databases. Within a cohort of men older than age 66 years with incident diabetes who subsequently developed PC, we examined the effect of duration of antidiabetic medication exposure after PC diagnosis on all-cause and PC-specific mortality. Crude and adjusted hazard ratios (HRs) were calculated by using a time-varying Cox proportional hazard model to estimate effects. The cohort consisted of 3,837 patients. Median age at diagnosis of PC was 75 years (interquartile range [IQR], 72 to 79 years). During a median follow-up of 4.64 years (IQR, 2.7 to 7.1 years), 1,343 (35%) died, and 291 patients (7.6%) died as a result of PC. Cumulative duration of metformin treatment after PC diagnosis was associated with a significant decreased risk of PC-specific and all-cause mortality in a dose-dependent fashion. Adjusted HR for PC-specific mortality was 0.76 (95% CI, 0.64 to 0.89) for each additional 6 months of metformin use. The association with all-cause mortality was also significant but declined over time from an HR of 0.76 in the first 6 months to 0.93 between 24 and 30 months. There was no relationship between cumulative use of other antidiabetic drugs and either outcome. Increased cumulative duration of metformin exposure after PC diagnosis was associated with decreases in both all-cause and PC-specific mortality among diabetic men.


Potential capacity of endoscopic screening for gastric cancer in Japan.
In 2016, the Japanese government decided to introduce endoscopic screening for gastric cancer as a national program. To provide endoscopic screening nationwide, we estimated the proportion of increase in the number of endoscopic examinations with the introduction of endoscopic screening, based on a national survey. The total number of endoscopic examinations has increased, particularly in clinics. Based on the national survey, the total number of participants in gastric cancer screening was 3 784 967. If 30% of the participants are switched from radiographic screening to endoscopic screening, approximately 1 million additional endoscopic examinations are needed. In Japan, the participation rates in gastric cancer screening and the number of hospitals and clinics offering upper gastrointestinal endoscopy vary among the 47 prefectures. If the participation rates are high and the numbers of hospitals and clinics are small, the proportion of increase becomes larger. Based on the same assumption, 50% of big cities can provide endoscopic screening with a 5% increase in the total number of endoscopic examinations. However, 16.7% of the medical districts are available for endoscopic screening within a 5% increase in the total number of endoscopic examinations. Despite the Japanese government's decision to introduce endoscopic screening for gastric cancer nationwide, its immediate introduction remains difficult because of insufficient medical resources in rural areas. This implies that endoscopic screening will be initially introduced to big cities. To promote endoscopic screening for gastric cancer nationwide, the disparity of medical resources must first be resolved.


Do longer root hairs improve phosphorus uptake? Testing the hypothesis with transgenic Brachypodium distachyon lines overexpressing endogenous RSL genes.
Mutants without root hairs show reduced inorganic orthophosphate (Pi) uptake and compromised growth on soils when Pi availability is restricted. What is less clear is whether root hairs that are longer than wild-type provide an additional benefit to phosphorus (P) nutrition. This was tested using transgenic Brachypodium lines with longer root hairs. The lines were transformed with the endogenous BdRSL2 and BdRSL3 genes using either a constitutive promoter or a root hair-specific promoter. Plants were grown for 32 d in soil amended with various Pi concentrations. Plant biomass and P uptake were measured and genotypes were compared on the basis of critical Pi values and P uptake per unit root length. Ectopic expression of RSL2 and RSL3 increased root hair length three-fold but decreased plant biomass. Constitutive expression of BdRSL2, but not expression of BdRSL3, consistently improved P nutrition as measured by lowering the critical Pi values and increasing Pi uptake per unit root length. Increasing root hair length through breeding or biotechnology can improve P uptake efficiency if the pleotropic effects on plant biomass are avoided. Long root hairs, alone, appear to be insufficient to improve Pi uptake and need to be combined with other traits to benefit P nutrition.


Molecular structure and transcriptional regulation of the gene for the platelet-derived growth factor alpha receptor in cultured vascular smooth muscle cells.
PDGF has been shown to contribute to hypertrophy in vascular smooth muscle cells (VSMC). PDGF-AA differentially promotes protein synthesis in VSMC from spontaneously hypertensive rats (SHR) but not in those from Wistar-Kyoto rats (WKY). This observation has led us to postulate a role for PDGF alpha receptor (PDGFR-alpha) in the hypertensive hypertrophy of blood vessels. Western and Northern blot analyses demonstrated a high and specific expression of the PDGFR-alpha protein and mRNA in SHR cells but not in WKY cells. To clarify the mechanism of the differential expression of the PDGFR-alpha gene, we isolated the promoter region of the gene. Studies on the promoter functions indicated that this promoter is active in SHR cells but not in WKY cells. The regulatory domain responsible for this difference was narrowed to the sequence between -246 and -139, which enhanced the promoter activity of SHR fivefold over the basal activity. DNase I footprinting and gel-shift assay indicated that this sequence specifically interact with nuclear proteins from VSMC through the binding site for CCAAT/enhancer-binding proteins, and members of the C/enhancer-binding protein family play a significant role in the strain-specific transcription of the PDGFR-alpha gene.


Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests.
The objective of this study was to compare celiac disease (CD)- specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed.


Imatinib mesylate radiosensitizes human glioblastoma cells through inhibition of platelet-derived growth factor receptor.
Imatinib mesylate is a small molecule inhibitor of the c-Abl, platelet-derived growth factor (PDGF) receptor and c-Kit tyrosine kinases that is approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and gastrointestinal stromal tumors. Glioblastoma multiforme is a highly malignant primary brain tumor that is usually treated with surgery and/or radiotherapy. Previous studies implicate an autocrine loop caused by high expression of PDGF and its receptor, PDGFR, in the proliferation of some glioblastomas. Here, we demonstrate that pretreatment of a human glioblastoma cell line, RuSi RS1, with imatinib significantly enhanced the cytotoxic effect of ionizing radiation. This effect was not seen in human breast cancer (BT20) and colon cancer (WiDr) cell lines. Whereas c-Abl and c-Kit were expressed about equally in the three cell lines, RuSi RS1 cells showed significantly higher expression of PDGFR-beta protein in comparison to BT20 and WiDr. Imatinib treatment of RuSi RS1 cells decreased overall levels of cellular tyrosine phosphorylation and specifically inhibited phosphorylation of PDGFR-beta, while c-Abl was not prominently activated in these cells. These results suggest that imatinib may have clinical utility as a radiosensitizer in the treatment of human glioblastoma, possibly through disruption of an autocrine PDGF/PDGFR loop.


"First do no harm." A systematic review of the prevalence and management of antipsychotic adverse effects.
We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25-50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy - one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed. There is a need for further scientific study concerning the management of these side effects.


Structural and mechanistic insights into ATRX-dependent and -independent functions of the histone chaperone DAXX.
The ATRX-DAXX histone chaperone complex incorporates the histone variant H3.3 at heterochromatic regions in a replication-independent manner. Here, we present a high-resolution x-ray crystal structure of an interaction surface between ATRX and DAXX. We use single amino acid substitutions in DAXX that abrogate formation of the complex to explore ATRX-dependent and ATRX-independent functions of DAXX. We find that the repression of specific murine endogenous retroviruses is dependent on DAXX, but not on ATRX. In support, we reveal the existence of two biochemically distinct DAXX-containing complexes: the ATRX-DAXX complex involved in gene repression and telomere chromatin structure, and a DAXX-SETDB1-KAP1-HDAC1 complex that represses endogenous retroviruses independently of ATRX and H3.3 incorporation into chromatin. We find that histone H3.3 stabilizes DAXX protein levels and can affect DAXX-regulated gene expression without incorporation into nucleosomes. Our study demonstrates a nucleosome-independent function for the H3.3 histone variant.


Trends in use of medical services by the elderly in British Columbia.
We analysed physician fee-for-service use in British Columbia from 1974-75 to 1985-86. Over the study period use increased by 5.3% per year. This can be factored into increases attributable to changes in the age structure of the population (0.4% per year), general population growth (1.8%, for a combined annual "population effect" of 2.2%) and age-specific increases in per-capita use (3% per year). The average annual increase for people aged 75 years or more was 5.5% per capita. The area with the fastest growth in use by the elderly was specialist care, particularly diagnostic services. The average number of specialists seen by people aged 75 years or more doubled over the study period. Our results suggest that increased per-capita use among the elderly that is unrelated to aging of the population should be the main focus of future policy attention. Additional analyses are needed to determine the underlying dynamics of this dramatic increase in rates of use among the elderly.


Submicrometer defect detection in periodic structures by photorefractive holography: system design and performance.
We have built an adaptive system capable of detecting submicrometer defects in periodic structures by using real-time holography in photorefractive crystals. We summarize the design and optimization of the defect-enhancement system. We present representative results of 0.2- to 0.5-µm diameter defect detection on two different periodic substrates: chrome-on-glass masks and patterned silicon wafers. On patterned silicon we detect 94% of the 0.5-µm diameter defects with three false positives, while inspecting an area greater than 1 mm(2) in 20 s or less. The throughput on the glass masks is somewhat less. To the best of our knowledge, these defects have an area 100 times smaller than those previously detected with any real-time holographic technique.


[Spontaneous intracranial hypotension syndrome].
Spontaneous Intracranial Hypotension is a rare syndrome, characterized by orthostatic headaches, low CSF pressure and characteristic aspects on MRI. The authors describe a clinical case of Spontaneous Intracranial Hypotension, in which the MRI investigation revealed a low position of the cerebellar tonsils, a diffuse and symmetric dural enhancement and an engorgement of the cervical epidural venous plexus. The authors make a review of the physiopathology, clinical and radiological aspects related to this syndrome.


Ethnomedical science and African medical practice.
The ethnomedical sciences are ethnobotany, ethnobiology, ethnopharmacology and phytotherapy. These fields are concerned with medicinal plants only, and the traditional medicines are mostly used. The author has extended the ethnomedical sciences by using traditional medicines in ethnomedicine, bacteriology, ethnobotany, and biochemistry, and thus ethnomedical sciences can be studied by a modern approach. The traditional doctors play a significant part in health care. They have both black and white patients, and they treat about 60%-70% of black patients in the country. Though they have been treating patients for many years, the patients' employers do not accept traditional doctors' medical certificates when they go back to work after treatment. In this case they first go to the traditional doctor for treatment and then go to an academically qualified medical practitioner solely because they need a medical certificate for their employers. Traditional doctors have been practising for centuries. In this country they are known as inyanga or ngaka and these designations mean doctor. Umthakathi or moloi means witch. Witchdoctor translates as Inyanga-mthakathi of ngaka-moloi.


The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies.
Tumor cells exploit their microenvironment by growth factors and cytokines such as vascular endothelial growth factor (VEGF) to stimulate abnormal vessel formation that is leaky and tortuous, causing irregular blood flow. The combination of poor perfusion, raised interstitial fluid pressure and areas of vascular collapse leads to hypoxia within tumor. The latter activates factors such as hypoxia inducible factor 1 (HIF-1) that serve to make cancer cells more aggressive and also markedly influences the response of malignant tumors to conventional irradiation and chemotherapy. Accumulating data now suggest that blockade of oncogenic signaling, for example by PI3K/Akt/mTOR inhibitors, might consist a promising strategy since these agents do not only possess antitumor effects but can also alter tumor vasculature and oxygenation to improve the response to radiation and chemotherapy. In many cases, these changes are related to downregulation of HIF-1α and VEGF. Here, we review the pathophysiology of tumor microenvironment (TME) and how it adversely affects cancer treatment. The complex interaction of tumor vasculature and radiotherapy is examined together the preclinical evidence supporting a proinvasive/metastatic role for ionising radiation. We will discuss the expanding role of oncogenic signaling, especially PI3K/Akt/mTOR, on tumor angiogenesis. Special emphasis will be paid to the potential of different oncogenic pathways blockade and other indirect antivascular strategies to alter the TME for the benefit of cancer treatment, as an alternative to the classical angiogenetic treatment.


Effects of Incorporating Carboxymethyl Chitosan into PMMA Bone Cement Containing Methotrexate.
Treatment of bone metastases usually includes surgical resection with local filling of methotrexate (MTX) in polymethyl methacrylate (PMMA) cement. We investigated whether incorporating carboxymethyl chitosan (CMCS) in MTX-PMMA cement might overcome disadvantages associated with MTX. To determine the optimal CMCS+MTX concentration to suppress the viability of cancer cells, an integrated microfluidic chip culturing highly metastatic lung cancer cells (H460) was employed. The mechanical properties, microstructure, and MTX release of (CMCS+MTX)-PMMA cement were evaluated respectively by universal mechanical testing machine, scanning electron microscopy (SEM), and incubation in simulated body fluid with subsequent HPLC-MS. Implants of MTX-PMMA and (CMCS+MTX)-PMMA cement were evaluated in vivo in guinea pig femurs over time using spiral computed tomography with three-dimensional image reconstruction, and SEM at 6 months. Viability of H460 cells was significantly lowest after treatment with 57 μg/mL CMCS + 21 μg/mL MTX, which was thus used in subsequent experiments. Incorporation of 1.6% (w/w) CMCS to MTX-PMMA significantly increased the bending modulus, bending strength, and compressive strength by 5, 2.8, and 5.2%, respectively, confirmed by improved microstructural homogeneity. Incorporation of CMCS delayed the time-to-plateau of MTX release by 2 days, but increased the fraction released at the plateau from 3.24% (MTX-PMMA) to 5.34%. Relative to the controls, the (CMCS+MTX)-PMMA implants integrated better with the host bone. SEM revealed pores in the cement of the (CMCS+MTX)-PMMA implants that were not obvious in the controls. In conclusion, incorporation of CMCS in MTX-PMMA appears a feasible and effective modification for improving the anti-tumor properties of MTX-PMMA cement.


Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report.
A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.


Infant feeding in Mali, West Africa: variations in belief and practice.
Research conducted in Mali during 1982 and 1983 reveals a wide range of variation in both the growth and development of infants and infant feeding practices. Overall, growth patterns of the Malian children (N = 136) are similar to those reported for children in other West African urban or rural poor populations. However, the use of the averages of growth measures disguises the fact that some children are severely malnourished, while others are growing at or above the 50th percentile of NCHS standards. Socio-economic status, as an indicator of the family's financial ability to provide food and medical care, does not account for the variation in nutritional status. From a series of open-ended interviews with mothers, fathers and other relatives of children in the study, as well as observation of mealtimes, several fundamental beliefs regarding infant feeding can be identified: (1) a child does not need to eat solid food before approx. 8 months; (2) if a child is hungry, he will eat, if he does not want to eat he should not be forced to eat; and (3) only the child himself knows when he is hungry and when he is full. These beliefs are expressed in the community in a variety of specific practices and behaviors. Additionally, mothers differ with respect to the importance they attach to medical care for sick children. These various beliefs and practices concerning infant feeding and, tangentially, medical care, tend to form divergent clusters, which allows the ranking of women on a three level scale of 'maternal attitude.' In the sample, growth performance, as indicated by membership in 'low weight' or 'high weight' groups, is positively correlated with maternal attitude (Chi2 = 13.85, P = 0.001). It is clear that in Mali, the cultural belief system regarding infant feeding and the variations in implementation of this system reflected in maternal attitudes, play an important role in determining the nutritional status and growth patterns of children, primarily through their effect on diet, and secondarily through their effect on medical care. The data show that within the same general cultural framework, and in the face of abject poverty, subtle differences in maternal attitudes result in some children who thrive, while others suffer varying degrees of malnutrition.


Cimetidine prevents reduction in gastric mucosal blood flow during shock.
This study evaluated Cimetidine's possible role in regulating gastric mucosal blood flow in the anesthetized, stressed miniature swine. Stress consisted of hemorrhagic shock to a mean arterial pressure of 50 mm Hg. Twenty-one animals were divided into three experimental groups: untreated controls, preshock Cimetidine treatment group, and postshock Cimetidine treatment group. Gastric mucosal blood flows were determined (microsphere method) during a stabilization period and after 90 minutes of shock. Central hemodynamic indices were monitored throughout each experiment. In the fundus, mucosal blood flow decreased 59% in the controls, 11% in the preshock, and 28% in the postshock Cimetidine groups. Antral mucosal blood flow decreased 57% in controls, 19% in the preshock, and 33% in the postshock Cimetidine groups. In the corpal mucosa, blood flow decreased 53% in controls, 11% in the preshock group, and 41% in the postshock Cimetidine group. Cimetidine administration, both before and after shock, conferred significant protection on mucosal blood flow changes related to shock. Preshock drug administration had a significantly greater protective effect than postshock treatment on blood flow in the corpal mucosa.


Treating individuals 3: from subgroups to individuals: general principles and the example of carotid endarterectomy.
Clinicians often have to make treatment decisions based on the likelihood that an individual patient will benefit. In this article we consider the relevance of relative and absolute risk reductions, and draw attention to the importance of expressing the results of trials and subgroup analyses in terms of absolute risk. We describe the limitations of univariate subgroup analysis in situations in which there are several determinants of treatment effect, and review the potential for targeting treatments with risk models, especially when benefit is probably going to be dependent on the absolute risk of adverse outcomes with or without treatment. The ability to systematically take into account the characteristics of an individual patient and their interactions, to consider the risks and benefits of interventions separately if needed, and to provide patients with personalised estimates of their likelihood of benefit is shown using the example of endarterectomy for symptomatic carotid stenosis.


A stable metallic state of (TTPCOO)2NH4 with a mobile dopant.
Ammonium tetrathiapentalene carboxylate [(TTPCOO)2NH4] was prepared via protonic defect-induction doping without electrochemical oxidation. The high electric conductivity of 13 S cm(-1) and Pauli paramagnetic-like behavior of magnetic susceptibility in a wide temperature range exhibit a melting of the charge degrees of freedom induced by a mobile dopant in a salt bridge. Solid-state (1)H NMR strongly indicates a stable metallic state of this compound down to 4 K.


Cerebral-autoregulatory dysfunction syndrome.
Reversible cerebral vasoconstriction syndrome and reversible posterior leukoencephalopathy syndrome are distinct clinicoradiological disorders which share certain features in terms of aetiology, pathogenesis and symptomatology. We present a case of a young primigravida with eclampsia who developed severe headache, vision loss and hemiparesis in the postpartum phase. MRI of the brain was suggestive of the involvement of anterior as well as posterior circulation and reversibility of widespread angiographic constrictions could be documented on follow-up. Despite the resolution of vascular changes, vision loss did not improve significantly in our case. Such an overlap of findings is unusual and probably represents the spectrum of cerebral-autoregulatory dysfunction occurring in these two syndromes.


Factors determining pulmonary function in adolescent idiopathic thoracic scoliosis.
Adolescent idiopathic thoracic scoliosis may lead to severe pulmonary impairment and early death, but the responsible factors are poorly understood; pulmonary function is only weakly related to the angle of scoliosis. We performed a cross-sectional study using multivariate analysis to identify the individual and additive influence of different features of spinal deformity and nonstructural factors on pulmonary impairment. Pulmonary function was assessed by measuring lung volumes and diffusing capacity, with a priori selection of vital capacity (expressed as percentage of predicted, % VC) as the primary index of pulmonary impairment. Radiologic and physiologic measurements were made independently in 66 subjects who had not previously had spinal surgery. Angle of scoliosis (p = 0.01) was one of four features of spinal deformity associated with reduced % VC; greater number of vertebrae involved (p = 0.007), cephadal location of the curve (p = 0.04), and loss of the normal thoracic kyphosis (p = 0.002) made an equal and additive contribution to pulmonary impairment. Spinal deformity led to reductions in VC, primarily by reducing TLC. Spinal column rotation, respiratory muscle strength, and duration of the curvature were not related to pulmonary function (p > 0.05). We conclude that features of the spinal deformity are the major determinants of pulmonary impairment in idiopathic thoracic scoliosis but that the relationship between deformity and impairment is complex. The severity of pulmonary impairment cannot be inferred to a clinically useful extent from the angle of scoliosis alone.


Reducing implicit racial preferences: I. A comparative investigation of 17 interventions.
Many methods for reducing implicit prejudice have been identified, but little is known about their relative effectiveness. We held a research contest to experimentally compare interventions for reducing the expression of implicit racial prejudice. Teams submitted 17 interventions that were tested an average of 3.70 times each in 4 studies (total N = 17,021), with rules for revising interventions between studies. Eight of 17 interventions were effective at reducing implicit preferences for Whites compared with Blacks, particularly ones that provided experience with counterstereotypical exemplars, used evaluative conditioning methods, and provided strategies to override biases. The other 9 interventions were ineffective, particularly ones that engaged participants with others' perspectives, asked participants to consider egalitarian values, or induced a positive emotion. The most potent interventions were ones that invoked high self-involvement or linked Black people with positivity and White people with negativity. No intervention consistently reduced explicit racial preferences. Furthermore, intervention effectiveness only weakly extended to implicit preferences for Asians and Hispanics.


Impact of hepatitis C virus infection on children and their caregivers: quality of life, cognitive, and emotional outcomes.
Hepatitis C virus (HCV) infection is associated with decreased quality of life (QOL) and neurocognitive dysfunction in adults, but little is known about its impact on children and their caregivers. We studied the QOL, behavioral, emotional, and cognitive functioning of 114 treatment-naïve children with HCV enrolled in a placebo-controlled, randomized, multisite clinical trial evaluating peginterferon alpha-2a alone or with ribavirin. Baseline assessment included measures of children's QOL, cognitive functioning, behavioral adaptation, and depression. Caregivers' QOL also was assessed. Relative to published normative data, caregivers were more likely to believe that their children's health was poor and would likely worsen (t = 3.93; P < 0.0001), and reported higher concern about their children's health status (t = 6.63; P < 0.0001) and that this concern limited family activities (t = 2.45; P < 0.01); they also viewed their children as having more internalizing behavioral problems (t = 1.98; P < 0.05). Only 2 (2%) children had a score in the clinically depressed range. Children with HCV had worse cognitive functioning than the normative sample but significantly better functioning than children with attention-deficit/hyperactivity disorder. Caregivers' QOL scores did not differ significantly from the normative sample, but infected mothers had lower QOL than noninfected caregivers. Caregivers were highly distressed about their children's medical circumstances. Although HCV infection, in its early stages, does not lead to global impairment in QOL, cognitive, behavioral, or emotional functioning in children, it is associated with higher caregiver stress and strain on the family system, and it may be associated with some cognitive changes in children.


Quantitative profiling of Drosophila melanogaster Dscam1 isoforms reveals no changes in splicing after bacterial exposure.
The hypervariable Dscam1 (Down syndrome cell adhesion molecule 1) gene can produce thousands of different ectodomain isoforms via mutually exclusive alternative splicing. Dscam1 appears to be involved in the immune response of some insects and crustaceans. It has been proposed that the diverse isoforms may be involved in the recognition of, or the defence against, diverse parasite epitopes, although evidence to support this is sparse. A prediction that can be generated from this hypothesis is that the gene expression of specific exons and/or isoforms is influenced by exposure to an immune elicitor. To test this hypothesis, we for the first time, use a long read RNA sequencing method to directly investigate the Dscam1 splicing pattern after exposing adult Drosophila melanogaster and a S2 cell line to live Escherichia coli. After bacterial exposure both models showed increased expression of immune-related genes, indicating that the immune system had been activated. However there were no changes in total Dscam1 mRNA expression. RNA sequencing further showed that there were no significant changes in individual exon expression and no changes in isoform splicing patterns in response to bacterial exposure. Therefore our studies do not support a change of D. melanogaster Dscam1 isoform diversity in response to live E. coli. Nevertheless, in future this approach could be used to identify potentially immune-related Dscam1 splicing regulation in other host species or in response to other pathogens.