Understanding primary care transformation and implications for ageing populations and health inequalities: a systematic scoping review of new models of primary health care in OECD countries and China.

BACKGROUND: Many countries have introduced reforms with the aim of primary care transformation (PCT). Common objectives include meeting service delivery challenges associated with ageing populations and health inequalities. To date, there has been little research comparing PCT internationally. Our aim was to examine PCT and new models of primary care by conducting a systematic scoping review of international literature in order to describe major policy changes including key 'components', impacts of new models of care, and barriers and facilitators to PCT implementation. METHODS: We undertook a systematic scoping review of international literature on PCT in OECD countries and China (published protocol: https://osf.io/2afym ). Ovid [MEDLINE/Embase/Global Health], CINAHL Plus, and Global Index Medicus were searched (01/01/10 to 28/08/21). Two reviewers independently screened the titles and abstracts with data extraction by a single reviewer. A narrative synthesis of findings followed. RESULTS: A total of 107 studies from 15 countries were included. The most frequently employed component of PCT was the expansion of multidisciplinary teams (MDT) (46% of studies). The most frequently measured outcome was GP views (27%), with < 20% measuring patient views or satisfaction. Only three studies evaluated the effects of PCT on ageing populations and 34 (32%) on health inequalities with ambiguous results. For the latter, PCT involving increased primary care access showed positive impacts whilst no benefits were reported for other components. Analysis of 41 studies citing barriers or facilitators to PCT implementation identified leadership, change, resources, and targets as key themes. CONCLUSIONS: Countries identified in this review have used a range of approaches to PCT with marked heterogeneity in methods of evaluation and mixed findings on impacts. Only a minority of studies described the impacts of PCT on ageing populations, health inequalities, or from the patient perspective. The facilitators and barriers identified may be useful in planning and evaluating future developments in PCT.

Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Premature or early bilateral oophorectomy: a 2021 update.

In this invited review, we discuss some unresolved and controversial issues concerning premature (<40 years) or early (40-45 years) bilateral oophorectomy. First, we clarify the terminology. Second, we summarize the long-term harmful consequences of bilateral oophorectomy. Third, we discuss the restrictive indications for bilateral oophorectomy in premenopausal women to prevent ovarian cancer that are justified by the current scientific evidence. Fourth, we explain the importance of estrogen replacement therapy when bilateral oophorectomy is performed. Hormone replacement therapy is indicated after bilateral oophorectomy until the age of expected natural menopause like in premature or early primary ovarian insufficiency. Fifth, we discuss the relationship between adverse childhood experiences, adverse adult experiences, mental health, gynecologic symptoms and bilateral oophorectomy. The acceptance and popularity of bilateral oophorectomy over several decades, and its persistence even in the absence of supporting scientific evidence, suggest that non-medical factors related to sex, gender, reproduction, cultural beliefs and socioeconomic structure are involved. We discuss some of these non-medical factors and the need for more research in this area.

The discrimination of quick Paediatric Early Warning Scores in the pre-hospital setting.

In our previous study, a Paediatric Early Warning Score could be calculated for only one-fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3-5 components. The discrimination of these 12 scores for the primary outcome (30-day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2-3% in about one third of children from the other children who had < 1% rate of outcome.

Safety and efficacy of the selective progesterone receptor modulator asoprisnil for heavy menstrual bleeding with uterine fibroids: pooled analysis of two 12-month, placebo-controlled, randomized trials.

STUDY QUESTION: Can asoprisnil, a selective progesterone receptor modulator, provide clinically meaningful improvements in heavy menstrual bleeding (HMB) associated with uterine fibroids with an acceptable safety profile? SUMMARY ANSWER: Uninterrupted treatment with asoprisnil for 12 months effectively controlled HMB and reduced fibroid and uterine volume with few adverse events. WHAT IS KNOWN ALREADY: In a 3-month study, asoprisnil (5, 10 and 25 mg) suppressed uterine bleeding, reduced fibroid and uterine volume, and improved hematological parameters in a dose-dependent manner. STUDY DESIGN, SIZE, DURATION: In two Phase 3, double-blind, randomized, placebo-controlled, multicentre studies, women received oral asoprisnil 10 mg, asoprisnil 25 mg or placebo (2:2:1) once daily for up to 12 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal women ≥18 years of age in North America with HMB associated with uterine fibroids were included (N = 907). The primary efficacy endpoint was the percentage of women who met all three predefined criteria at 12 months or the final month for patients who prematurely discontinued: (1) ≥50% reduction in monthly blood loss (MBL) by menstrual pictogram, (2) hemoglobin concentration ≥11 g/dL or an increase of ≥1 g/dL, and (3) no interventional therapy for uterine fibroids. Secondary efficacy endpoints included changes in other menstrual bleeding parameters, volume of the largest fibroids, uterine volume and health-related quality of life (HRQL). MAIN RESULTS AND THE ROLE OF CHANCE: In all, 90% and 93% of women in the asoprisnil 10-mg and 25-mg groups, respectively, and 35% of women in the placebo group met the primary endpoint (P < 0.001). Similar results were observed at month 6 (P < 0.001). The percentage of women who achieved amenorrhea in any specified month ranged from 66-78% in the asoprisnil 10-mg group and 83-93% in the asoprisnil 25-mg group, significantly higher than with placebo (3-12%, P < 0.001). Hemoglobin increased rapidly (by month 2) with asoprisnil treatment and was significantly higher versus placebo throughout treatment. The primary fibroid and uterine volumes were significantly reduced from baseline through month 12 with asoprisnil 10 mg (median changes up to -48% and -28%, respectively) and 25 mg (median changes up to -63% and -39%, respectively) versus placebo (median changes up to +16% and +13%, respectively; all P < 0.001). Dose-dependent, significant improvements in HRQL (Uterine Fibroid Symptom and Quality of Life instrument) were observed with asoprisnil treatment. Asoprisnil was generally well tolerated. Endometrial biopsies indicated dose- and time-dependent decreases in proliferative patterns and increases in quiescent or minimally stimulated endometrium at month 12 of treatment. Although not statistically significantly different at month 6, mean endometrial thickness at month 12 increased by ~2 mm in both asoprisnil groups compared with placebo (P < 0.01). This effect was associated with cystic changes in the endometrium on MRI and ultrasonography, which led to invasive diagnostic and therapeutic procedures in some asoprisnil-treated women. LIMITATIONS, REASONS FOR CAUTION: Most study participants were black; few Asian and Hispanic women participated. The study duration may have been insufficient to fully characterize the endometrial effects. WIDER IMPLICATIONS OF THE FINDINGS: Daily uninterrupted treatment with asoprisnil was highly effective in controlling menstrual bleeding, improving anemia, reducing fibroid and uterine volume, and increasing HRQL in women with HMB associated with uterine fibroids. However, this treatment led to an increase in endometrial thickness and invasive diagnostic and therapeutic procedures, with potential unknown consequences. STUDY FUNDING/COMPETING INTEREST(S): This trial was funded by AbbVie Inc. (prior sponsors: TAP Pharmaceutical Products Inc., Abbott Laboratories). E.A. Stewart was a site investigator in the Phase 2 study of asoprisnil and consulted for TAP during the design and conduct of these studies while at Harvard Medical School and Brigham and Women's Hospital. She received support from National Institutes of Health grants HD063312, HS023418 and HD074711 and research funding, paid to Mayo Clinic for patient care costs related to an NIH-funded trial from InSightec Ltd. She consulted for AbbVie, Allergan, Bayer HealthCare AG, Gynesonics, and Welltwigs. She received royalties from UpToDate and the Med Learning Group. M.P. Diamond received research funding for the conduct of the studies paid to the institution and consulted for AbbVie. He is a stockholder and board and director member of Advanced Reproductive Care. He has also received funding for study conduct paid to the institution from Bayer and ObsEva. A.R.W. Williams consulted for TAP and Repros Therapeutics Inc. He has current consultancies with PregLem SA, Gedeon Richter, HRA Pharma and Bayer. B.R. Carr consulted for and received research funding from AbbVie. E.R. Myers consulted for AbbVie, Allergan and Bayer. R.A. Feldman received compensation for serving as a principal investigator and participating in the conduct of the trial. W. Elger was co-inventor of several patents related to asoprisnil. C. Mattia-Goldberg is a former employee of AbbVie and may own AbbVie stock or stock options. B.M. Schwefel and K. Chwalisz are employees of AbbVie and may own AbbVie stock or stock options. TRIAL REGISTRATION NUMBER: NCT00152269, NCT00160381 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 7 September 2005; 8 September 2005. DATE OF FIRST PATIENT'S ENROLMENT: 12 September 2002; 6 September 2002.

Structure and Dynamics of the Methane-Propane van der Waals Complex.

Microwave transitions in the region 7-26 GHz were measured for the methane-propane van der Waals complex. The nearly free internal rotation of methane within the complex gives rise to three states that do not relax even in a 5 K supersonic expansion. Eighteen lines have been assigned to the lowest state and are well fitted to a semirigid rotor model, with rotational constants A = 7553.8229 (24) MHz, B = 2483.9200 (8) MHz, and C = 2041.8692 (5) MHz, and six distortion constants. The structure has the methane positioned above the plane defined by the propane carbon atoms with a center-of-mass van der Waals bond distance of 3.98 Å. This is significantly larger than the equilibrium value of 3.71 Å found with ab initio calculations done at the CCSD(T)-F12a/aug-cc-pVTZ level of theory. Further calculations encompassing a large range of angular orientations of the methane subunit indicate that angular motion produces a large zero-point contribution to the energy, which not only lowers the effective barrier to internal rotation of the methane but also increases the radial distance between subunits. Therefore, although in the lowest energy structure the methane can get close to the propane by interdigitating the hydrogens atoms, the zero-point energy effectively flattens out the potential so that the hydrogens become less restricting.

Calibration lamp design, characterization, and implementation for the Michelson Interferometer for Global High-Resolution Thermospheric Imaging instrument on the Ionospheric Connection satellite.

We describe the design and ground-based performance of the two-color calibration lamp for the Michelson Interferometer for Global High-Resolution Thermospheric Imaging (MIGHTI) instrument on the NASA Ionospheric Connection (ICON) satellite. The calibration lamp assembly contains radio frequency excited krypton and neon lamps, which generate emission lines at 557 and 630 nm, respectively, and which are used to monitor thermal drifts in the two MIGHTI Doppler asymmetric spatial heterodyne interferometers. The lamps are coupled to two mixed optical fiber bundles that deliver the calibration signals to the two MIGHTI optical units. The assembly starts reliably, consumes <8 W, and has passed environmental testing for the ICON satellite. The total mass of the lamp assembly is 1.8 kg. Special features of the assembly and its implementation are described along with results of life tests.

Integrating HIV care and treatment into tuberculosis clinics in Lusaka, Zambia: results from a before-after quasi-experimental study.

BACKGROUND: Patients with HIV-associated tuberculosis (TB) often have their TB and HIV managed in separate vertical programs that offer care for each disease with little coordination. Such "siloed" approaches are associated with diagnostic and treatment delays, which contribute to unnecessary morbidity and mortality. To improve TB/HIV care coordination and early ART initiation, we integrated HIV care and treatment into two busy TB clinics in Zambia. We report here the effects of our intervention on outcomes of linkage to HIV care, early ART uptake, and TB treatment success for patients with HIV-associated TB in Lusaka, Zambia. METHODS: We provided integrated HIV treatment and care using a "one-stop shop" model intervention. All new or relapse HIV-positive TB patients were offered immediate HIV program enrolment and ART within 8 weeks of anti-TB therapy (ATT) initiation. We used a quasi-experimental design, review of routine program data, and survival analysis and logistic regression methods to estimate study outcomes before (June 1, 2010-January 31, 2011) and after (August 1, 2011-March 31, 2012) our intervention among 473 patients with HIV-associated TB categorized into pre- (n = 248) and post-intervention (n = 225) cohorts. RESULTS: Patients in the pre- and post-intervention cohorts were mostly male (60.1% and 52.9%, respectively) and young (median age: 33 years). In time-to-event analyses, a significantly higher proportion of patients in the post-intervention cohort linked to HIV care by 4 weeks post-ATT initiation (53.9% vs. 43.4%, p = 0.03), with median time to care linkage being 59 and 25 days in the pre- and post-intervention cohorts, respectively. In Cox proportional hazard modelling, patients receiving the integration intervention started ART by 8 weeks post-ATT at 1.33 times the rate (HR = 1.33, 95% CI: 1.00-1.77) as patients pre-intervention. In logistic regression modelling, patients receiving the intervention were 2.02 times (95% CI: 1.11-3.67) as likely to have a successful TB treatment outcome as patients not receiving the intervention. CONCLUSIONS: Integrating HIV treatment and care services into routine TB clinics using a one-stop shop model increased linkage to HIV care, rates of early ART initiation, and TB treatment success among patients with HIV-associated TB in Lusaka, Zambia.

Torsional splitting and the four-fold barrier to internal rotation: The rotational spectra of vinylsulfur pentafluoride.

Vinylsulfur pentafluoride (VSPF), a molecule with a four-fold internal rotor, -SF4, has been studied with high resolution Fourier transform microwave spectroscopy. We believe that this is the first report of resolved four-fold internal rotation. As such, we have presented the tools needed to understand and analyze such a problem. These include debugging the ERHAM computer program necessary to fit the spectra and the free rotor to high barrier correlation diagram necessary to understand the torsional states of the four-fold rotor. The A, E, and B torsional state rotational transitions are well resolved and assigned. Spectroscopic transitions of four isotopologues of VSPF, H2C=CH-SF5, the normal isotopologue, and the singly substituted 34S and 13C isotopologues were measured and assigned. Contrary to expectation, the A torsional state could not be fit with only a semi-rigid Hamiltonian. The barrier to internal rotation, V 4, is found to be 227 cm-1. Ab initio calculations at the MP2 aug-cc-pVQZ level of theory and basis set were performed and the results of this calculation are compared to our experimental results.

Migration and protest in the Jim Crow South.

The Great Migration and the Civil Rights Movement were two pivotal events experienced by the southern African American population during the 20th Century. Each has received considerable attention by social scientists and historians, and a possible connection between the two phenomena has been speculated. However, no systematic investigation of the effect of migration on protest during the Jim Crow era has been conducted. In this study we use data for 333 southern communities to examine the relationship between youthful black migration between 1950 and 1960 and the occurrence of sit-ins early in 1960. We find a strong positive, non-linear, relationship between net-migration and the likelihood of a sit-in which can be explained by two sets of mediating influences: local demographic conditions and local organizational presence. Our findings offer strong empirical support for an association between southern black migration and protest during Jim Crow and suggest the value of considering the influence of demographic forces on collective action.

Prevention of transmission of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis in prisoners.

The prevalence of HIV, hepatitis B virus, hepatitis C virus, and tuberculosis are higher in prisons than in the general population in most countries worldwide. Prisons have emerged as a risk environment for these infections to be further concentrated, amplified, and then transmitted to the community after prisoners are released. In the absence of alternatives to incarceration, prisons and detention facilities could be leveraged to promote primary and secondary prevention strategies for these infections to improve prisoners health and reduce risk throughout incarceration and on release. Effective treatment of opioid use disorders with opioid agonist therapies (eg, methadone and buprenorphine) prevents blood-borne infections via reductions in injection in prison and after release. However, large gaps exist in the implementation of these strategies across all regions. Collaboration between the criminal justice and public health systems will be required for successful implementation of these strategies.

Limited impact of awareness-raising campaigns on hepatitis C testing practices among general practitioners.

The global hepatitis strategy calls for increased effort to diagnose those infected, with a target of 90% diagnosed by 2030. Scotland's Action Plan on Hepatitis C included awareness-raising campaigns, undertaken during 2008-2011, to promote testing by general practitioners. We examined hepatitis C virus (HCV) testing practice among general practitioners before and following these campaigns. Scottish general practitioners were surveyed, using Dillman's method, in 2007 and 2013; response rates were 69% and 60%, respectively. Most respondents offer testing when presented with a risk history (86% in 2007, 88% in 2013) but only one-fifth actively sought out risk factors (19% in 2007, 21% in 2013). Testing was reportedly always/almost always/usually offered to people who inject drugs (84% in 2007, 87% in 2013). Significant improvements in the offer of testing were reported in patients with abnormal LFTs (41% in 2007, 65% in 2013, P<.001) and who had received medical/dental treatment in high prevalence countries (14% in 2007, 24% in 2013, P=.001). In 2013, 25% of respondents had undertaken HCV-related continued professional development. This group was significantly more likely to actively seek out risk factors (P=.009) but only significantly more likely to offer a test to patients who had received medical/dental treatment in high prevalence countries (P=.001). Our findings suggest that government-led awareness raising campaigns have limited impact on general practitioners' testing practices. If the majority of the HCV-infected population are to be diagnosed, practitioner-based or physician-centred interventions should be considered alongside educational initiatives targeted at professionals.

Epidemiology of uterine fibroids: a systematic review.

BACKGROUND: Uterine fibroids (UFs) are the most common neoplasm affecting women that can cause significant morbidity and may adversely impact fertility. OBJECTIVES: To examine UF epidemiology and to evaluate the relative strengths of putative risk factors. SEARCH STRATEGY: MEDLINE and Embase were searched for studies published in English between January 1995 and April 2015. SELECTION CRITERIA: Publications reporting relevant data from registries and other observational studies with over 1000 patients and single-centre studies with over 100 patients were selected. DATA COLLECTION AND ANALYSIS: Data on UF incidence, prevalence and associated risk factors were extracted from 60 publications. MAIN RESULTS: Wide ranges were reported in both UF incidence (217-3745 cases per 100 000 women-years) and prevalence (4.5-68.6%), depending on study populations and diagnostic methods. Black race was the only factor that was recurrently reported to increase UF risk, by two-threefold compared with white race. Eleven other factors affected UF risk to a magnitude similar to or greater than race. Age, premenopausal state, hypertension, family history, time since last birth, and food additive and soybean milk consumption increased UF risk; use of oral contraceptives or the injectable contraceptive depot medroxyprogesterone acetate, smoking in women with low body mass index and parity reduced UF risk. CONCLUSIONS: We identified 12 risk factors that play an important role in UF epidemiology. The UF risk factor with the strongest evidence is black race. High-quality prospective observational data are needed to improve our understanding of UF epidemiology, and thus its aetiology and optimal management. TWEETABLE ABSTRACT: Uterine fibroids occur in about 70% of women. Black race and 11 other factors affect uterine fibroid risk.

Medical therapies for heavy menstrual bleeding in women with uterine fibroids: a retrospective analysis of a large commercially insured population in the USA.

OBJECTIVES: To report patterns and patient characteristics associated with initiation of and persistence with medical therapies for uterine fibroid-related heavy menstrual bleeding. DESIGN: Retrospective cohort study. SETTING: US commercial insurance claims database. POPULATION: 41 561 women aged 18-54 years with uterine fibroids and heavy menstrual bleeding who initiated medical therapies from January 2000 through December 2013. METHOD: Multinomial logistic regression was used to assess patient characteristics associated with initiation and persistence. Cox proportional hazards regression was used on propensity score-matched cohorts to examine change from index medication. MAIN OUTCOMES MEASURES: Initiation of and persistence with four first-line medical therapies: short- and long-acting reversible contraceptive steroids, leuprolide acetate, and tranexamic acid. RESULTS: Most women (79.4%) took short-acting reversible contraceptive steroids as first-line therapy (index medication), whereas 9.5%, 8.5%, and 2.7% used long-acting reversible contraceptive steroids, leuprolide acetate, and tranexamic acid, respectively. During follow-up, 16 594 women (39.9%) switched to nonindex medication (18.4%) or procedural treatment (81.6%). In comparison with women taking short-acting steroids, those receiving long-acting steroids were less likely to switch [hazard ratio (HR) 0.84, 95% CI 0.79-0.91], whereas women taking leuprolide acetate (HR 2.44, 95% CI 2.27-2.62) or tranexamic acid (HR 1.44, 95% CI 1.26-1.65) were more likely to switch. Older age, emergency department visits, anaemia, and inflammatory disease diagnoses at baseline were associated with increased probability of discontinuing the index medication or switching to another therapy. CONCLUSIONS: Women with uterine fibroid-related heavy menstrual bleeding were more likely to persist with their initial therapy of long-acting reversible contraceptive steroid compared with other medical options. TWEETABLE ABSTRACT: 80% women with fibroid-related heavy menstrual bleeding use SARC, but LARC users are more persistent.

The covalent interaction between dihydrogen and gold: A rotational spectroscopic study of H2-AuCl.

The pure rotational transitions of H2-AuCl have been measured using a pulsed-jet cavity Fourier transform microwave spectrometer equipped with a laser ablation source. The structure was found to be T-shaped, with the H-H bond interacting with the gold atom. Both 35Cl and 37Cl isotopologues have been measured for both ortho and para states of H2. Rotational constants, quartic centrifugal distortion constants, and nuclear quadrupole coupling constants for gold and chlorine have been determined. The use of the nuclear spin-nuclear spin interaction terms Daa, Dbb, and Dcc for H2 were required to fit the ortho state of hydrogen, as well as a nuclear-spin rotation constant Caa. The values of the nuclear quadrupole coupling constant of gold are χaa=-817.9929(35) MHz, χbb=504.0(27) MHz, and χcc=314.0(27). This is large compared to the eQq of AuCl, 9.63 312(13) MHz, which indicates a strong, covalent interaction between gold and dihydrogen.

Examining the Psychometric Properties of the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire in Two Samples of Youth with OCD.

Researchers have demonstrated that quality of life (QOL) is an important construct to measure in individuals with mental health disorders, yet only a small amount of research has been dedicated to examining QOL and its response to treatment in children and adolescents with obsessive-compulsive disorder (OCD). The current study explored the psychometric properties of a measure of QOL, the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), by examining the reliability, validity, and treatment sensitivity of this measure delivered in two separate RCTs for OCD (total N = 251 across both studies). Our results provide evidence for the reliability and validity of the PQ-LES-Q in adolescents with OCD (all Cronbach's alphas >.89, convergent validity correlations significant at the p < .05 level), but that an adaptation of the measure many be necessary for valid use in younger children with OCD.

Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia.

OBJECTIVE: Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population from full-term placental tissue and were previously shown to possess anti-inflammatory and immunomodulatory properties. PDACs (formulated as PDA-002) are in clinical trials for peripheral arterial disease with diabetic foot ulcer. In the current study, we examined their angiogenic and tissue reparative properties. METHODS: The effects of PDACs on survival and tube formation of human umbilical vein endothelial cells (HUVECs) were tested using conditioned media and noncontact coculture. Angiogenic effects were assessed in the chick chorioallantoic membrane assay. Hindlimb ischemia (HLI) was induced in mice and rats by femoral artery transection, and blood flow and blood vessel density were monitored in vivo by laser Doppler and angiography in the ischemic and control limbs. Tissue damage and regeneration in HLI were examined in histologic sections of quadriceps muscle stained with hematoxylin and eosin, and newly synthesized blood vessels were detected by indoxyl-tetrazolium staining for alkaline phosphatase. RESULTS: PDACs enhanced the survival of serum-starved HUVECs and stimulated HUVEC tube formation, and in the chick chorioallantoic membrane assay, PDACs stimulated blood vessel formation. In HLI, intramuscular administration of PDACs resulted in improved blood flow and vascular density, and in quadriceps muscle, tissue regeneration and increased numbers of blood vessels were observed. CONCLUSIONS: PDACs exhibited various activities consistent with angiogenesis and tissue repair, supporting the continued investigation of this cell therapy as treatment for vascular disease-related indications.

Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.

QTL mapping of temperature sensitivity reveals candidate genes for thermal adaptation and growth morphology in the plant pathogenic fungus Zymoseptoria tritici.

Different thermal environments impose strong, differential selection on populations, leading to local adaptation, but the genetic basis of thermal adaptation is poorly understood. We used quantitative trait locus (QTL) mapping in the fungal wheat pathogen Zymoseptoria tritici to study the genetic architecture of thermal adaptation and identify candidate genes. Four wild-type strains originating from the same thermal environment were crossed to generate two mapping populations with 263 (cross 1) and 261 (cross 2) progeny. Restriction site-associated DNA sequencing was used to genotype 9745 (cross 1) and 7333 (cross 2) single-nucleotide polymorphism markers segregating within the mapping population. Temperature sensitivity was assessed using digital image analysis of colonies growing at two different temperatures. We identified four QTLs for temperature sensitivity, with unique QTLs found in each cross. One QTL had a logarithm of odds score >11 and contained only six candidate genes, including PBS2, encoding a mitogen-activated protein kinase kinase associated with low temperature tolerance in Saccharomyces cerevisiae. This and other QTLs showed evidence for pleiotropy among growth rate, melanization and growth morphology, suggesting that many traits can be correlated with thermal adaptation in fungi. Higher temperatures were highly correlated with a shift to filamentous growth among the progeny in both crosses. We show that thermal adaptation has a complex genetic architecture, with natural populations of Z. tritici harboring significant genetic variation for this trait. We conclude that Z. tritici populations have the potential to adapt rapidly to climate change and expand into new climatic zones.

Chest radiograph reading and recording system: evaluation in frontline clinicians in Zambia.

BACKGROUND: In Zambia the vast majority of chest radiographs (CXR) are read by clinical officers who have limited training and varied interpretation experience, meaning lower inter-rater reliability and limiting the usefulness of CXR as a diagnostic tool. In 2010-11, the Zambian Prison Service and Ministry of Health established TB and HIV screening programs in six prisons; screening included digital radiography for all participants. Using front-line clinicians we evaluated sensitivity, specificity and inter-rater agreement for digital CXR interpretation using the Chest Radiograph Reading and Recording System (CRRS). METHODS: Digital radiographs were selected from HIV-infected and uninfected inmates who participated in a TB and HIV screening program at two Zambian prisons. Two medical officers (MOs) and two clinical officers (COs) independently interpreted all CXRs. We calculated sensitivity and specificity of CXR interpretations compared to culture as the gold standard and evaluated inter-rater reliability using percent agreement and kappa coefficients. RESULTS: 571 CXRs were included in analyses. Sensitivity of the interpretation "any abnormality" ranged from 50-70 % depending on the reader and the patients' HIV status. In general, MO's had higher specificities than COs. Kappa coefficients for the ratings of "abnormalities consistent with TB" and "any abnormality" showed good agreement between MOs on HIV-uninfected CXRs and moderate agreement on HIV-infected CXRs whereas the COs demonstrated fair agreement in both categories, regardless of HIV status. CONCLUSIONS: Sensitivity, specificity and inter-rater agreement varied substantially between readers with different experience and training, however the medical officers who underwent formal CRRS training had more consistent interpretations.