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This study explored the extent to which organisations responsible for initial teacher training, prepare pre-service teachers to deliver comprehensive sexuality education in schools. Five electronic databases were searched to identify publications that reported the provision of CSE training for pre-service teachers. Methodological quality was appraised using The Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Descriptive analyses were conducted to summarise the scope of pre-service teacher preparation. Twenty-two documents, primarily from the UK, Australia and the USA were identified for review. Overall, information regarding training in comprehensive sexuality education for pre-service teachers is limited. The review identified wide variability in training content and positioning in primary and/or secondary programmes as either core or elective requirements. Current provision does not appear to align with international and best-practice guidelines in most instances. Further research and greater transparency regarding the preparation of pre-service teachers to deliver comprehensive sexuality education is recommended to identify and prioritise best-practice holistic teaching concepts to improve teacher and student outcomes.

Introduction: Families have a significant role in the lives of people with intellectual disabilities and challenging behaviors. However, it is not clear how actively families are involved when people with intellectual disabilities and challenging behaviors are living in out-of-home care. This scoping review explored the frequency and type of family involvement in the application of a person-centered approach in the care for people with intellectual disabilities and challenging behaviors. Methods: Authors conducted electronic searches through six databases: Embase, Medline, Web of Science, PsycINFO, Cochrane Central, and Google Scholar (2005 to 2019) and evaluated relevant publications. Results: Based on the 15 articles identified, only five articles report on family involvement. In addition, frequency of contact, and how family is involved appears to differ between different person-centered approaches. Conclusion: More active family involvement in person-centered approaches for people with intellectual disabilities and challenging behaviors is recommended.

Following significant intelligence failures, the United States intelligence community adopted Intelligence Community Directive 203 (ICD203) to promote analytic rigor. We developed two psychometric scales to examine how strongly intelligence professionals (N = 108) endorsed the analytic standards comprising ICD203 and how strongly they believed their organizations complied with these standards. All ICD203 facets were highly endorsed and clustered into three principal components, and perceived organizational compliance was high. Facets reflecting intelligence aims were endorsed more strongly than those reflecting means. ICD203 endorsement was positively related to conscientious and actively open-minded thinking, whereas perceived organizational compliance was positively correlated with conscientiousness, job satisfaction, and affective and normative commitment. [ABSTRACT FROM AUTHOR]

Background: Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available.Objective: To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate.Design: Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561).Setting: United States.Participants: 100 healthy adult volunteers.Intervention: Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo.Measurements: Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model.Results: All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model.Limitation: The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population.Conclusion: The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges.Primary Funding Source: Janssen Vaccines and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Study Question: To what extent do characteristics of germline genome editing (GGE) determine whether the general public supports permitting the clinical use of GGE?Summary Answer: The risk that GGE would cause congenital abnormalities had the largest effect on support for allowing GGE, followed by effectiveness of GGE, while costs, the type of application (disease or enhancement) and the effect on child well-being had moderate effects.What Is Known Already: Scientific progress on GGE has increased the urgency of resolving whether and when clinical application of GGE may be ethically acceptable. Various expert bodies have suggested that the treatment characteristics will be key in determining whether GGE is acceptable. For example, GGE with substantial risks (e.g. 15% chance of a major congenital abnormality) may be acceptable to prevent a severe disease but not to enhance non-medical characteristics or traits of an otherwise healthy embryo (e.g. eye colour or perhaps in the future more complex traits, such as intelligence). While experts have called for public engagement, it is unclear whether and how much the public acceptability of GGE is affected by the treatment characteristics proposed by experts.Study Design, Size, Duration: The vignette-based survey was disseminated in 2018 among 1857 members of the Dutch general public. An online research panel was used to recruit a sample representing the adult Dutch general public.Participants/materials, Setting, Methods: A literature review identified the key treatment characteristics of GGE: the effect on the well-being of the future child, use for disease or enhancement, risks for the future child, effectiveness (here defined as the chance of a live birth, assuming that if the GGE was not successful, the embryo would not be transferred), cost and availability of alternative treatments/procedures to prevent the genetic disease or provide enhancement (i.e. preimplantation genetic testing (PGT)), respectively. For each treatment characteristic, 2-3 levels were defined to realistically represent GGE and its current alternatives, donor gametes and ICSI with PGT. Twelve vignettes were created by fractional factorial design. A multinominal logit model assessed how much each treatment characteristic affected participants' choices.Main Results and the Role Of Chance: The 1136 respondents (response rate 61%) were representative of the Dutch adult population in several demographics. Respondents were between 18 and 89 years of age. When no alternative treatment/procedure is available, the risk that GGE would cause (other) congenital abnormalities had the largest effect on whether the Dutch public supported allowing GGE (coefficient = -3.07), followed by effectiveness (coefficient = 2.03). Costs (covered by national insurance, coefficient = -1.14), the type of application (disease or enhancement; coefficient = -1.07), and the effect on child well-being (coefficient = 0.97) had similar effects on whether GGE should be allowed. If an alternative treatment/procedure (e.g. PGT) was available, participants were not categorically opposed to GGE, however, they were strongly opposed to using GGE for enhancement (coefficient = -3.37). The general acceptability of GGE was higher than participants' willingness to personally use it (P < 0.001). When participants considered whether they would personally use GGE, the type of application (disease or enhancement) was more important, whereas effectiveness and costs (covered by national insurance) were less important than when they considered whether GGE should be allowed. Participants who were male, younger and had lower incomes were more likely to allow GGE when no alternative treatment/procedure is available.Limitations, Reasons For Caution: Some (e.g. ethnic, religious) minorities were not well represented. To limit complexity, not all characteristics of GGE could be included (e.g. out-of-pocket costs), therefore, the views gathered from the vignettes reflect only the choices presented to the respondents. The non-included characteristics could be connected to and alter the importance of the studied characteristics. This would affect how closely the reported coefficients reflect 'real-life' importance.Wider Implications Of the Findings: This study is the first to quantify the substantial impact of GGE's effectiveness, costs (covered by national insurance), and effect on child well-being on whether the public considered GGE acceptable. In general, the participants were strikingly risk-averse, in that they weighed the risks of GGE more heavily than its benefits. Furthermore, although only a single study in one country, the results suggests that-if sufficiently safe and effective-the public may approve of using GGE (presumably combined with PGT) instead of solely PGT to prevent passing on a disease. The reported public views can serve as input for future consideration of the ethics and governance of GGE.Study Funding/competing Interest(s): Young Academy of the Royal Dutch Academy of Sciences (UPS/RB/745), Alliance Grant of the Amsterdam Reproduction and Development Research Institute (2017-170116) and National Institutes of Health Intramural Research Programme. No competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Ectopic pregnancy occurs when a fertilized ovum implants outside of the uterine cavity. In the United States, the estimated prevalence of ectopic pregnancy is 1% to 2%, and ruptured ectopic pregnancy accounts for 2.7% of pregnancy-related deaths. Risk factors include a history of pelvic inflammatory disease, cigarette smoking, fallopian tube surgery, previous ectopic pregnancy, and infertility. Ectopic pregnancy should be considered in any patient presenting early in pregnancy with vaginal bleeding or lower abdominal pain in whom intrauterine pregnancy has not yet been established. The definitive diagnosis of ectopic pregnancy can be made with ultrasound visualization of a yolk sac and/or embryo in the adnexa. However, most ectopic pregnancies do not reach this stage. More often, patient symptoms combined with serial ultrasonography and trends in beta human chorionic gonadotropin levels are used to make the diagnosis. Pregnancy of unknown location refers to a transient state in which a pregnancy test is positive but ultrasonography shows neither intrauterine nor ectopic pregnancy. Serial beta human chorionic gonadotropin levels, serial ultrasonography, and, at times, uterine aspiration can be used to arrive at a definitive diagnosis. Treatment of diagnosed ectopic pregnancy includes medical management with intramuscular methotrexate, surgical management via salpingostomy or salpingectomy, and, in rare cases, expectant management. A patient with diagnosed ectopic pregnancy should be immediately transferred for surgery if she has peritoneal signs or hemodynamic instability, if the initial beta human chorionic gonadotropin level is high, if fetal cardiac activity is detected outside of the uterus on ultrasonography, or if there is a contraindication to medical management. [ABSTRACT FROM AUTHOR]

Background: The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen.Methods: Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme.Results: This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes.Conclusions: Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology. [ABSTRACT FROM AUTHOR]

At the beginning of the 1960s, it was clear that a vaccine against measles would soon be available. Although measles was (and remains) a killer disease in the developing world, in the United States and Western Europe this was no longer so. Many parents and many medical practitioners considered measles an inevitable stage of a child's development. Debating the desirability of measles immunization, public health experts reasoned differently. In the United States, introduction of the vaccine fit well with Kennedy's and Johnson's administrations' political commitments. European policymakers proceeded cautiously, concerned about the acceptability of existing vaccination programs. In Sweden and the Netherlands, recent experience in controlling polio led researchers to prefer an inactivated virus vaccine. Although in the early 1970s attempts to develop a sufficiently potent inactivated vaccine were abandoned, we have argued that the debates and initiatives of the time during the vaccine's early history merit reflection in today's era of standardization and global markets. [ABSTRACT FROM AUTHOR]

When comparing health care providers, patient experience data are usually adjusted for case-mix associations to ensure fair comparisons. Previous studies in the United States showed that case-mix associations sometimes vary across health care providers. Such variation could indicate differential provider behavior for patient subgroups, in which case current adjustment techniques might be inappropriate. To see whether this variation is also apparent in a health care system different from the U.S. system, the authors analyzed Dutch patients’ experiences with family practice care. Using multilevel random slope models, the associations between age, general health status, mental health status, education, sex, and ethnicity on one hand and reported experiences on the other hand were assessed across family practices. The authors found only five significant variances between case-mix coefficients, all for outcomes related to health care professionals’ conduct. These findings correspond to previous U.S. findings, suggesting that the case-mix variations reported here and previously constitute a rather robust phenomenon. [ABSTRACT FROM AUTHOR]

Public support for civil liberties has undergone important changes in the past 50 years, as has scholarship on this topic. Whereas the American public was very intolerant of communists, socialists, and atheists in the 1950s and 1960s, current intolerance is now focused more on Muslim Americans and right-wing racists, among other groups. What has remained consistent is the important role played in shaping citizens' tolerant and intolerant attitudes by their individual characteristics, such as education, authoritarianism, dogmatism, religiosity, and race. Although threat perceptions have always played an important role in explaining citizens' support for civil liberties, this variable has gained new meaning in the aftermath of the terrorist attacks of September 11, 2001. Meanwhile, improved survey methodology now allows us to understand better the extent of democratic tolerance among Americans. In this article, we review the state of the literature on public support for civil liberties prior to 9/11 and, because we believe the terrorist attacks dramatically changed the political context, after 9/11. [ABSTRACT FROM AUTHOR]

Examines the coping style of psychiatric patients during cognitive behavioral group therapies. Effects of mood and anxiety disorders on coping style changes; Non-relation of coping style and drug abuse severity; Focus on anxiety disorder during substance abuse treatment to improve coping style.

Focuses on external factors affecting the business cycles in the United States. International capital flow in the 1980s; Portfolio inflows and outflows into the country; Banking flows.

Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control.Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete.Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression).Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network. [ABSTRACT FROM AUTHOR]

The United States of America and the European Countries have responded quite differently to the to the human rights of candidate workers as imposed by genetic and predictive health testing. Whereas the United States traditionally relies largely on the non-discrimination principle, the European countries seem to attach more value to the right to privacy and the principle of social justice. A recently published communication of the Commission of the European Communities seems to bridge these two legal traditions.