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Purpose: This study aims to introduce the perceived systems intelligence (SI) inventory, developed based on the earlier published self-report SI inventory (Törmänen et al., 2016). It can be used together with earlier managerial level tools for building a learning organization and included in general 360-style evaluations in personnel development. Design/methodology/approach: The inventory is validated with confirmatory factor analysis with a model based on the self-report SI inventory, using data from full-time used employees and managers in the USA and UK. Perceived SI factor scores are correlated with the perceived study performance of the individual. Findings: The perceived SI inventory is found to have good factorial validity, and it correlates strongly with evaluations of perceived study performance. Managers perceived high in performance are also found to score high in perceived SI. Perceived SI does not depend on gender, age, organization size or industry. Originality/value: The perceived SI inventory is the first personnel level peer evaluation tool suggested for developing learning organizations. The new inventory makes peer evaluations possible and provides a new grassroots level tool for personnel development programs in learning organizations.

Importance: Cardiovascular disease (CVD) is the leading cause of morbidity and death in the US and is the cause of more than 1 of every 4 deaths. Coronary heart disease is the single leading cause of death and accounts for 43% of deaths attributable to CVD in the US. In 2019, an estimated 558 000 deaths were caused by coronary heart disease and 109 000 deaths were caused by ischemic stroke.Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality or all-cause mortality.Population: Adults 40 years or older without a history of known CVD and who do not have signs and symptoms of CVD.Evidence Assessment: The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD event risk of 10% or greater has at least a moderate net benefit. The USPSTF concludes with moderate certainty that statin use for the prevention of CVD events and all-cause mortality in adults aged 40 to 75 years with no history of CVD and who have 1 or more of these CVD risk factors and an estimated 10-year CVD event risk of 7.5% to less than 10% has at least a small net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of statin use for the primary prevention of CVD events and mortality in adults 76 years or older with no history of CVD.Recommendation: The USPSTF recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors (ie, dyslipidemia, diabetes, hypertension, or smoking) and an estimated 10-year CVD risk of 10% or greater. (B recommendation) The USPSTF recommends that clinicians selectively offer a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more of these CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%. The likelihood of benefit is smaller in this group than in persons with a 10-year risk of 10% or greater. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating a statin for the primary prevention of CVD events and mortality in adults 76 years or older. (I statement). [ABSTRACT FROM AUTHOR]

Importance: Dental caries is the most common chronic disease in children in the US. According to the 2011-2016 National Health and Nutrition Examination Survey, approximately 23% of children aged 2 to 5 years had dental caries in their primary teeth. Prevalence is higher in Mexican American children (33%) and non-Hispanic Black children (28%) than in non-Hispanic White children (18%). Dental caries in early childhood is associated with pain, loss of teeth, impaired growth, decreased weight gain, negative effects on quality of life, poor school performance, and future dental caries.Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on screening and interventions to prevent dental caries in children younger than 5 years.Population: Asymptomatic children younger than 5 years.Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit of preventing future dental caries with oral fluoride supplementation at recommended doses in children 6 months or older whose water supply is deficient in fluoride. The USPSTF concludes with moderate certainty that there is a moderate net benefit of preventing future dental caries with fluoride varnish application in all children younger than 5 years. The USPSTF concludes that the evidence is insufficient on performing routine oral screening examinations for dental caries by primary care clinicians in children younger than 5 years and that the balance of benefits and harms of screening cannot be determined.Recommendation: The USPSTF recommends that primary care clinicians prescribe oral fluoride supplementation starting at age 6 months for children whose water supply is deficient in fluoride. (B recommendation) The USPSTF recommends that primary care clinicians apply fluoride varnish to the primary teeth of all infants and children starting at the age of primary tooth eruption. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine screening examinations for dental caries performed by primary care clinicians in children younger than 5 years. (I statement). [ABSTRACT FROM AUTHOR]

Background: In this study we compared Swissmedic's (SMC's) regulatory marketing authorization decisions to those of the US Food and Drug Administration (FDA) and European drug regulatory authorities (EU). We investigated the overall similarity of the regulatory decisions, approval, and postmarketing withdrawal rates in the 3 jurisdictions. In case regulatory decisions diverged, we analyzed the reasons for rejection of marketing authorization applications (MAAs). Methods: The study comprises 255 new molecular entity (NME) MAAs assessed by SMC by the EU and FDA between 2005 through 2014. Study parameters included the regulatory decision, postmarketing withdrawal rates, and the official reasons for rejection. Results: Regulatory decisions converged to a high degree among all 3 agencies (between 84% and 90%). SMC's average approval rate (84%) was slightly lower than those of the FDA (87%) and the EU (91%). Postmarketing withdrawal rates were generally low (4%-5%) but were 3 to 5 times higher when decisions among the drug regulatory authorities (DRAs) diverged. SMC's primary grounds for rejection were lack of efficacy (45%) and safety (40%). Conclusions: The 3 investigated DRAs adhere largely to the same scientific principles and regulatory guidelines; therefore, remaining disparities ought to be considered in a cultural, legal and public health priority context. [ABSTRACT FROM AUTHOR]

Objective To investigate long-term body mass index (BMI) changes associated with childbearing. Design and Methods Adjusted mean BMI changes were estimated by race-ethnicity, baseline BMI, and parity using longitudinal regression models for 3,943 young females over 10 and 25 year follow-up from the ongoing 1979 National Longitudinal Survey of Youth cohort. Results Estimated BMI increases varied by group, ranging from a low of 2.1 BMI units for white, non-overweight nulliparas over the first 10 years to a high of 10.1 BMI units for black, overweight multiparas over the full 25-year follow-up. Impacts of parity were strongest among overweight multiparas and primaparas at 10 years, ranges 1.4-1.7 and 0.8-1.3 BMI units, respectively. Among non-overweight women, parity-related gain at 10 years varied by number of births among black and white but not Hispanic women. After 25 years, childbearing significantly increased BMI only among overweight multiparous black women. Conclusion Childbearing is associated with permanent weight gain in some women, but the relationship differs by maternal BMI in young adulthood, number of births, race-ethnicity, and length of follow-up. Given that overweight black women may be at special risk for accumulation of permanent, long-term weight after childbearing, effective interventions for this group are particularly needed. [ABSTRACT FROM AUTHOR]

A reprint is presented of a June 17, 2009 article on U.S. weapons sales to foreign countries posted on the Web site of the news agency Reuters. It reports that Jeffrey Wieringa, head of the Defense Security Cooperation Agency, forecast that government-to-government arms sales by the U.S. could increase to over $40 billion in 2009.

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well. [ABSTRACT FROM AUTHOR]

Biosimilar medicinal products (biosimilars) have become a reality in the European Union and will soon be available in the United States. Despite an established legal pathway for biosimilars in the European Union since 2005 and increasing and detailed regulatory guidance on data requirements for their development and licensing, many clinicians, particularly oncologists, are reluctant to consider biosimilars as a treatment option for their patients. Major concerns voiced about biosimilars relate to their pharmaceutical quality, safety (especially immunogenic-ity), efficacy (particularly in extrapolated indications), and interchangeability with the originator product. In this article, the members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) address these issues. A clear understanding of the scientific principles of the biosimilar concept and access to unbiased information on licensed biosimilars are important for physicians to make informed and appropriate treatment choices for their patients. This will become even more important with the advent of biosimilar monoclonal antibodies. The issues also highlight the need for improved communication between physicians, learned societies, and regulators. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepcidin is a potential biomarker for anemia of chronic diseases and disorders of iron metabolism. Thus, data of preanalytical factors, reference values and method characteristics are critical for clinical use of hepcidin determination. Methods: We studied the effects of sample storage, sampling device and a meal on hepcidin levels using a liquid-chromatography tandem mass spectrometric (LC–MS/MS) method for serum hepcidin. Age- and gender-dependent reference values were determined using serum samples from healthy volunteers (n=231). The results were also compared with those obtained by a commercial competitive ELISA for hepcidin. Results: In serum samples, hepcidin is stable for one day at room temperature, six days at +4°C and at least 42days at −20°C. Breakfast or type of sampling device does not affect hepcidin concentration. Significantly lower hepcidin concentrations were observed in women ≤50 than >50years of age or in men (p<0.0001 for both). Reference values for females aged 18–50years were 0.4–9.2nmol/L, for those >50years 0.7–16.8nmol/L and for males ≥18years 1.1–15.6nmol/L. Comparison with a competitive ELISA showed poor correlation. Conclusions: Fasting before sampling and type of blood collection were not critical. Samples can be transported to laboratory at room temperature if they arrive within a day. Significantly lower concentrations of serum hepcidin were observed in menstruating than in post-menopausal women and in men. [Copyright &y& Elsevier]

The research is limited to the role of African American (AA) fathers in maternal health. African American fathers are largely not included in perinatal care, and their contribution may be essential in addressing the Black maternal health disparity crisis. The purpose of this conceptual paper is to examine the evidence of African American fathers involvement in supporting maternal health during the perinatal period. This conceptual paper will summarize research findings and will focus on 1) the evolution of the concept of fatherhood and the role of African American fathers; 2) the extent of African American fathers engagement during the perinatal period; and 3) the potential for African American fathers to play a key role in improving maternal health. Findings from this paper will enhance the evidence base on fathers' involvement in maternal health, highlight the research gaps, and opportunities to focus on African American fathers in addressing maternal morbidity and mortality among African American women.

Background: Preeclampsia is associated with increased cardiovascular morbidity and death. Primary care or cardiology follow-up, in complement to routine postpartum obstetric care, provides an essential opportunity to address cardiovascular risk. Prior studies investigating racial differences in the recommended postpartum follow-up have incompletely assessed the influence of social factors. We hypothesized that racial and ethnic differences in follow-up with a primary care provider or cardiologist would be modified by income and education., Methods and Results: We identified adult individuals with preeclampsia (September 2014 to September 2019) in a national administrative database. We compared occurrence of a postpartum visit with a primary care provider or cardiologist within 1 year after delivery by race and ethnicity using multivariable logistic regression models. We examined whether education or income modified the association between race and ethnicity and the likelihood of follow-up. Of 18 050 individuals with preeclampsia (aged 31.8±5.7 years), Black individuals (11.7%) had lower odds of primary care provider or cardiology follow-up within 1 year after delivery compared with White individuals (adjusted odds ratio, 0.77 [95% CI, 0.70-0.85]) as did Hispanic individuals (14.8%; adjusted odds ratio, 0.79 [95% CI, 0.73-0.87]). Black and Hispanic individuals with higher educational attainment were more likely to have follow-up than those with lower educational attainment ( P for interaction=0.033) as did those in higher income brackets ( P for interaction=0.006)., Conclusions: We identified racial and ethnic differences in primary care or cardiology follow-up in the year postpartum among individuals diagnosed with preeclampsia, a disparity that may be modified by social factors. Enhanced system-level interventions are needed to reduce barriers to follow-up care.

Importance: Falls are the leading cause of injury-related morbidity and mortality among older adults in the US. In 2018, 27.5% of community-dwelling adults 65 years or older reported at least 1 fall in the past year and 10.2% reported a fall-related injury. In 2021, an estimated 38 742 deaths resulted from fall-related injuries., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the effectiveness and harms of primary care-relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling adults 65 years or older., Population: Community-dwelling adults 65 years or older at increased risk of falls., Evidence Assessment: The USPSTF concludes with moderate certainty that exercise interventions provide a moderate net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls. The USPSTF concludes with moderate certainty that multifactorial interventions provide a small net benefit in preventing falls and fall-related morbidity in older adults at increased risk for falls., Recommendation: The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians individualize the decision to offer multifactorial interventions to prevent falls to community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient's values and preferences. (C recommendation).

Importance: Among all US women, breast cancer is the second most common cancer and the second most common cause of cancer death. In 2023, an estimated 43 170 women died of breast cancer. Non-Hispanic White women have the highest incidence of breast cancer and non-Hispanic Black women have the highest mortality rate., Objective: The USPSTF commissioned a systematic review to evaluate the comparative effectiveness of different mammography-based breast cancer screening strategies by age to start and stop screening, screening interval, modality, use of supplemental imaging, or personalization of screening for breast cancer on the incidence of and progression to advanced breast cancer, breast cancer morbidity, and breast cancer-specific or all-cause mortality, and collaborative modeling studies to complement the evidence from the review., Population: Cisgender women and all other persons assigned female at birth aged 40 years or older at average risk of breast cancer., Evidence Assessment: The USPSTF concludes with moderate certainty that biennial screening mammography in women aged 40 to 74 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening mammography in women 75 years or older and the balance of benefits and harms of supplemental screening for breast cancer with breast ultrasound or magnetic resonance imaging (MRI), regardless of breast density., Recommendation: The USPSTF recommends biennial screening mammography for women aged 40 to 74 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of supplemental screening for breast cancer using breast ultrasonography or MRI in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Objective: To determine the relative hazards of acute and chronic diabetes complications among people with diabetes across the U.S. rural-urban continuum., Research Design and Methods: This retrospective cohort study used the OptumLabs Data Warehouse, a deidentified data set of U.S. commercial and Medicare Advantage beneficiaries, to follow 2,901,563 adults (age ≥18 years) with diabetes between 1 January 2012 and 31 December 2021. We compared adjusted hazard ratios (HRs) of diabetes complications in remote areas (population <2,500), small towns (population 2,500-50,000), and cities (population >50,000)., Results: Compared with residents of cities, residents of remote areas had greater hazards of myocardial infarction (HR 1.06 [95% CI 1.02-1.10]) and revascularization (HR 1.04 [1.02-1.06]) but lower hazards of hyperglycemia (HR 0.90 [0.83-0.98]) and stroke (HR 0.91 [0.88-0.95]). Compared with cities, residents of small towns had greater hazards of hyperglycemia (HR 1.06 [1.02-1.10]), hypoglycemia (HR 1.15 [1.12-1.18]), end-stage kidney disease (HR 1.04 [1.03-1.06]), myocardial infarction (HR 1.10 [1.08-1.12]), heart failure (HR 1.05 [1.03-1.06]), amputation (HR 1.05 [1.02-1.09]), other lower-extremity complications (HR 1.02 [1.01-1.03]), and revascularization (HR 1.05 [1.04-1.06]) but a smaller hazard of stroke (HR 0.95 [0.94-0.97]). Compared with small towns, residents of remote areas had lower hazards of hyperglycemia (HR 0.85 [0.78-0.93]), hypoglycemia (HR 0.92 [0.87-0.97]), and heart failure (HR 0.94 [0.91-0.97]). Hazards of retinopathy and atrial fibrillation/flutter did not vary geographically., Conclusions: Adults in small towns are disproportionately impacted by complications of diabetes. Future studies should probe for the reasons underlying these disparities., (© 2024 by the American Diabetes Association.)

Importance: Child maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care-feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment., Population: Children and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement).

Distinct pedagogical approaches within medical curricula in France and in the U.S. reflect a growing recognition of the importance of nutrition to address major public health challenges. However, recent generations of medical students have expressed mixed opinions regarding nutrition education. What pedagogical approach may improve nutrition education? Despite different medical systems, students from both France and the U.S. share similar concerns and expectations, that nutrition knowledge must be embedded in the curriculum and must be engaging. Hands-on, system-based, epistemological, and multidisciplinary approaches need better articulation to forge a robust medical curriculum. In the rapidly changing contexts of medicine and public awareness, social science research may facilitate recommendations for improved nutrition education.

Importance: Oral health is fundamental to health and well-being across the lifespan. Oral health conditions affect the daily lives of school-age children and adolescents, leading to loss of more than 51 million school hours every year. Untreated oral health conditions in children can lead to serious infections and affect growth, development, and quality of life., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate screening and preventive interventions for oral health conditions in children and adolescents aged 5 to 17 years., Population: Asymptomatic children and adolescents aged 5 to 17 years., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for oral health conditions (eg, dental caries) performed by primary care clinicians in asymptomatic children and adolescents aged 5 to 17 years. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions for oral health conditions (eg, dental caries) performed by primary care clinicians in asymptomatic children and adolescents aged 5 to 17 years., Recommendations: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine screening performed by primary care clinicians for oral health conditions, including dental caries, in children and adolescents aged 5 to 17 years. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of preventive interventions performed by primary care clinicians for oral health conditions, including dental caries, in children and adolescents aged 5 to 17 years. (I statement).

Importance: An estimated 1.2 million persons in the US currently have HIV, and more than 760 000 persons have died of complications related to HIV since the first cases were reported in 1981. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of preexposure prophylaxis with antiretroviral therapy for the prevention of HIV acquisition, and the diagnostic accuracy of risk assessment tools to identify persons at increased risk of HIV acquisition., Population: Adolescents and adults who do not have HIV and are at increased risk of HIV., Evidence Assessment: The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV., Recommendation: The USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. (A recommendation).

Importance: Major depressive disorder (MDD), a common mental disorder in the US, may have substantial impact on the lives of affected individuals. If left untreated, MDD can interfere with daily functioning and can also be associated with an increased risk of cardiovascular events, exacerbation of comorbid conditions, or increased mortality., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of screening, accuracy of screening, and benefits and harms of treatment of MDD and suicide risk in asymptomatic adults that would be applicable to primary care settings., Population: Asymptomatic adults 19 years or older, including pregnant and postpartum persons. Older adults are defined as those 65 years or older., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for MDD in adults, including pregnant and postpartum persons and older adults, has a moderate net benefit. The USPSTF concludes that the evidence is insufficient on the benefit and harms of screening for suicide risk in adults, including pregnant and postpartum persons and older adults., Recommendation: The USPSTF recommends screening for depression in the adult population, including pregnant and postpartum persons and older adults. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for suicide risk in the adult population, including pregnant and postpartum persons and older adults. (I statement).

Importance: In the US, tuberculosis remains an important preventable disease, including active tuberculosis, which may be infectious, and latent tuberculosis infection (LTBI), which is asymptomatic and not infectious but can later progress to active disease. The precise prevalence rate of LTBI in the US is difficult to determine; however, estimated prevalence is about 5.0%, or up to 13 million persons. Incidence of tuberculosis varies by geography and living accommodations, suggesting an association with social determinants of health., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on LTBI screening and treatment in asymptomatic adults seen in primary care, as well as the accuracy of LTBI screening tests., Population: Asymptomatic adults 18 years or older at increased risk for tuberculosis., Evidence Assessment: The USPSTF concludes with moderate certainty that there is a moderate net benefit in preventing active tuberculosis disease by screening for LTBI in persons at increased risk for tuberculosis infection., Recommendation: The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).

The use of traditional faecal indicator bacteria as surrogate organisms for pathogenic viruses in domestic wastewater has been noted as a problematic as concentrations and removal rates of bacteria and viruses do not seem to correlate. In this sense, bacteriophages (phages) emerge as potential viral indicators, as they are commonly found in wastewater in high levels, and can be quantified using simple, fast, low-cost methods. Somatic and F-specific coliphages comprise groups of phages commonly used as indicators of water quality. There are two internationally recognised methods to detect and enumerate coliphages in water samples, the International Standardization Organization (ISO) and the US Environmental Protection Agency (USEPA) methods. Both methods are based on the lysis of specific bacterial host strains infected by phages. Within this context, this systematic literature review aimed at gathering concentrations in raw and treated domestic wastewater (secondary, biological treatment systems and post-treatment systems), and removal efficiencies of somatic and F-specific coliphages obtained by ISO and USEPA methods, and then compare both methods. A total of 33 research papers were considered in this study. Results showed that the ISO method is more commonly applied than the USEPA method. Some discrepancies in terms of concentrations and removal efficiencies were observed between both methods. Higher removal rates were observed for both somatic and F-specific coliphages in activated sludge systems when using the USEPA method compared to the ISO method; in other secondary (biological) treatment systems, this was observed only for F-specific coliphages. The use of different standardised methods available might lead to difficulties in obtaining and comparing phage data in different conditions and locations. Future research comparing both ISO and USEPA methods as well as viral and bacterial pathogens and indicators in WWTP is recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Studies have sought to evaluate factors that have perpetuated disparities in health care, including urogynecologic care. However, there remains a lack of understanding of barriers to care specific to racial/ethnic minority populations., Objectives: We aimed to report identified barriers to urogynecologic care (eg, care for symptoms/diagnoses of urinary incontinence [UI], accidental bowel leakage [ABL], and pelvic organ prolapse [POP]) for underrepresented racial and ethnic minority (URM) women in the United States., Study Design: We conducted a systematic search for studies through 5 electronic bibliographic databases. Inclusion criteria for eligible studies included the following: (1) studies reporting barriers to care for those with urogynecologic symptoms/diagnoses, (2) publication date year 2000 or later. Exclusion criteria included study cohorts with children, exclusively non-U.S. populations, cohorts without URM participants, and studies without qualitative research methodology. Study methodology, characteristics, as well as barriers and facilitators to urogynecologic care were captured using a thematic synthesis approach., Results: There were 360 studies identified. Twelve studies met criteria: 6 had study populations with UI, 3 with POP, 2 on UI and/or POP, and 1 on ABL. There were 7 focus group studies (total 44 groups, n = 330), 4 interview studies (total 160 interviews, n = 160), and 1 had both (10 interviews, 6 groups, n = 39). Most studies reported on patient-associated barriers (n = 10/12) and physician/provider-associated barriers (n = 10/12), whereas only half reported system-associated barriers (n = 6/12)., Conclusion: Identified barriers to urogynecologic care for URM populations were examined. Findings likely do not fully reflect barriers to urogynecologic care for URM populations. Comprehensive evaluation of social determinants of health and systemic racism within studies is needed to understand the unique barriers present for racially/ethnically diverse populations., Competing Interests: Conflict of Interest: M.F.A. is supported by NIH National Institute on Aging (R03AG064378-01, K23AG073517-01) and the Pennsylvania Department of Health (4100088553). M.F.A.'s spouse employed by Johnson & Johnson Corporate. E.M.D. is a member of the U.S. Preventive Services Task Force (USPSTF), and the views of this article should not be attributed to the USPSTF. Otherwise, the authors report no relevant conflicts of interest., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Importance: Current prevalence of obstructive sleep apnea (OSA) in the US is not well established; however, based on cohort and survey data, in 2007-2010 the estimated prevalence of at least mild OSA (defined as an apnea-hypoxia index [AHI] ≥5) plus symptoms of daytime sleepiness among adults aged 30 to 70 years was 14% for men and 5% for women, and the estimated prevalence of moderate to severe OSA (defined as AHI ≥15) was 13% for men and 6% for women. Severe OSA is associated with increased all-cause mortality. Other adverse health outcomes associated with untreated OSA include cardiovascular disease and cerebrovascular events, type 2 diabetes, cognitive impairment, decreased quality of life, and motor vehicle crashes., Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for OSA in adults., Population: Asymptomatic adults (18 years or older) and adults with unrecognized symptoms of OSA., Evidence Assessment: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in the general adult population. (I statement).

Importance: Anxiety disorder, a common mental health condition in the US, comprises a group of related conditions characterized by excessive fear or worry that present as emotional and physical symptoms. The 2018-2019 National Survey of Children's Health found that 7.8% of children and adolescents aged 3 to 17 years had a current anxiety disorder. Anxiety disorders in childhood and adolescence are associated with an increased likelihood of a future anxiety disorder or depression., Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for anxiety disorders in children and adolescents. This is a new recommendation., Population: Children and adolescents 18 years or younger who do not have a diagnosed anxiety disorder or are not showing recognized signs or symptoms of anxiety., Evidence Assessment: The USPSTF concludes with moderate certainty that screening for anxiety in children and adolescents aged 8 to 18 years has a moderate net benefit. The USPSTF concludes that the evidence is insufficient on screening for anxiety in children 7 years or younger., Recommendation: The USPSTF recommends screening for anxiety in children and adolescents aged 8 to 18 years. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for anxiety in children 7 years or younger. (I statement).

Importance: Syphilis is a sexually transmitted infection that can progress through different stages (primary, secondary, latent, and tertiary) and cause serious health problems if left untreated. Reported cases of primary and secondary syphilis in the US increased from a record low of 2.1 cases per 100 000 population in 2000 and 2001 to 11.9 cases per 100 000 population in 2019. Men account for the majority of cases (83% of primary and secondary syphilis cases in 2019), and rates among women nearly tripled from 2015 to 2019., Objective: To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focusing on targeted key questions evaluating the performance of risk assessment tools and the benefits and harms of screening for syphilis in nonpregnant adolescents and adults., Population: Asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at increased risk for syphilis infection., Evidence Assessment: Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection., Recommendation: The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).

A team of experts on the effects of the spaceflight environment on the brain and eye (SANS: Spaceflight-Associated Neuro-ocular Syndrome) was convened by NASA and ESA to (1) review spaceflight-associated structural and functional changes of the human brain and eye, and any interactions between the two; and (2) identify critical future research directions in this area to help characterize the risk and identify possible countermeasures and strategies to mitigate the spaceflight-induced brain and eye alterations. The experts identified 14 critical future research directions that would substantially advance our knowledge of the effects of spending prolonged periods of time in the spaceflight environment on SANS, as well as brain structure and function. They used a paired comparison approach to rank the relative importance of these 14 recommendations, which are discussed in detail in the main report and are summarized briefly below., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with some of the authors., (Copyright © 2022 Seidler, Stern, Basner, Stahn, Wuyts and zu Eulenburg.)

Importance: Cardiovascular disease (CVD), which includes heart disease, myocardial infarction, and stroke, is the leading cause of death in the US. A large proportion of CVD cases can be prevented by addressing modifiable risk factors, including smoking, obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower rates of cardiovascular morbidity and mortality than those who do not; however, most US adults do not consume healthy diets or engage in physical activity at recommended levels., Objective: To update its 2017 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions to promote healthy behaviors in adults without CVD risk factors., Population: Adults 18 years or older without known CVD risk factors, which include hypertension or elevated blood pressure, dyslipidemia, impaired fasting glucose or glucose tolerance, or mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater., Evidence Assessment: The USPSTF concludes with moderate certainty that behavioral counseling interventions have a small net benefit on CVD risk in adults without CVD risk factors., Recommendation: The USPSTF recommends that clinicians individualize the decision to offer or refer adults without CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (C recommendation).

Importance: Glaucoma affects an estimated 2.7 million people in the US. It is the second-leading cause of irreversible blindness in the US and the leading cause of blindness in Black and Hispanic/Latino persons., Objective: To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for glaucoma in adults., Population: Adults 40 years or older who present in primary care and do not have signs or symptoms of open-angle glaucoma., Evidence Assessment: The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for glaucoma in adults. The benefits and harms of screening for glaucoma in adults are uncertain. More research is needed., Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for primary open-angle glaucoma in adults. (I statement).

Importance: Chronic obstructive pulmonary disease (COPD) is an irreversible reduction of airflow in the lungs. Progression to severe disease can prevent participation in normal activities because of deterioration of lung function. In 2020 it was estimated that approximately 6% of US adults had been diagnosed with COPD. Chronic lower respiratory disease, composed mainly of COPD, is the sixth leading cause of death in the US., Objective: To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update that focused on targeted key questions for benefits and harms of screening for COPD in asymptomatic adults and treatment in screen-detected or screen-relevant adults., Population: Asymptomatic adults who do not recognize or report respiratory symptoms., Evidence Assessment: Using a reaffirmation process, the USPSTF concludes with moderate certainty that screening for COPD in asymptomatic adults has no net benefit., Recommendation: The USPSTF recommends against screening for COPD in asymptomatic adults. (D recommendation).

Importance: US life expectancy and health outcomes for preventable causes of disease have continued to lag in many populations that experience racism., Objective: To propose iterative changes to US Preventive Services Task Force (USPSTF) processes, methods, and recommendations and enact a commitment to eliminate health inequities for people affected by systemic racism., Design and Evidence: In February 2021, the USPSTF began operational steps in its work to create preventive care recommendations to address the harmful effects of racism. A commissioned methods report was conducted to inform this process. Key findings of the report informed proposed updates to the USPSTF methods to address populations adversely affected by systemic racism and proposed pilots on implementation of the proposed changes., Findings: The USPSTF proposes to consider the opportunity to reduce health inequities when selecting new preventive care topics and prioritizing current topics; seek evidence about the effects of systemic racism and health inequities in all research plans and public comments requested, and integrate available evidence into evidence reviews; and summarize the likely effects of systemic racism and health inequities on clinical preventive services in USPSTF recommendations. The USPSTF will elicit feedback from its partners and experts and proposed changes will be piloted on selected USPSTF topics., Conclusions and Relevance: The USPSTF has developed strategies intended to mitigate the influence of systemic racism in its recommendations. The USPSTF seeks to reduce health inequities and other effects of systemic racism through iterative changes in methods of developing evidence-based recommendations, with partner and public input in the activities to implement the advancements.

Background: We recently reported that a 6-day continuous peripheral nerve block reduced established postamputation phantom pain 3 weeks after treatment ended. However, the immediate effects of perineural infusion (secondary outcomes) have yet to be reported., Methods: Participants from 5 enrolling academic centers with an upper or lower limb amputation and established phantom pain received a single-injection ropivacaine peripheral nerve block(s) and perineural catheter insertion(s). They were subsequently randomized to receive a 6-day ambulatory perineural infusion of either ropivacaine 0.5% or normal saline in a double-masked fashion. Participants were contacted by telephone 1, 7, 14, 21, and 28 days after the infusion started, with pain measured using the Numeric Rating Scale. Treatment effects were assessed using the Wilcoxon rank-sum test at each time point. Adjusting for 4 time points (days 1, 7, 14, and 21), P < .0125 was deemed statistically significant. Significance at 28 days was reported using methods from the original, previously published article., Results: Pretreatment average phantom and residual pain scores were balanced between the groups. The day after infusion initiation (day 1), average phantom, and residual limb pain intensity was lower in patients receiving local anesthetic (n = 71) versus placebo (n = 73): median [quartiles] of 0 [0-2.5] vs 3.3 [0-5.0], median difference (98.75% confidence interval [CI]) of -1.0 (-3.0 to 0) for phantom pain (P = .001) and 0 [0-0] vs 0 [0-4.3], and median difference 0.0 (-2.0 to 0.0) for residual limb pain (P < .001). Pain's interference with physical and emotional functioning as measured with the interference domain of the Brief Pain Inventory improved during the infusion on day 1 for patients receiving local anesthetic versus placebo: 0 [0-10] vs 10 [0-40], median difference (98.75% CI) of 0.0 (-16.0 to 0.0), P = .002. Following infusion discontinuation (day 6), a few differences were found between the active and placebo treatment groups between days 7 and 21. In general, sample medians for average phantom and residual limb pain scores gradually increased after catheter removal for both treatments, but to a greater degree in the control group until day 28, at which time the differences between the groups returned to statistical significance., Conclusions: This secondary analysis suggests that a continuous peripheral nerve block decreases phantom and residual limb pain during the infusion, although few improvements were again detected until day 28, 3 weeks following catheter removal., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Unlabelled: Melanoma is a treatable and preventable skin cancer. It is responsible for 75% of deaths among all skin cancers. Previous studies have found that race/ethnicity may play a role in survival among melanoma patients. However, there are no studies that cover 30 years and take race into account for the U.S., Population: This study is a secondary analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) Program. Adults with primary cutaneous melanoma from 1982 to 2011 were included; the final sample size was 185,219. The outcome was survival; both cause-specific and all-cause mortality were examined. The main exposure was race/ethnicity. Kaplan-Meier survival analysis was used to estimate overall survival. Cox proportional hazards regression was used to estimate unadjusted and adjusted hazard ratios (HRs). A P-value less than 0.05 was considered statistically significant.More than 50% of patients in all races/ethnicities were diagnosed at the in situ or localized stage. Non-Hispanic White patients were more frequently diagnosed at the in situ stage. Overall, more men were diagnosed than women. The majority of cases among all races were men. Non-Hispanic Black females represented the smallest percentage of melanoma cases among all races. The smallest number of diagnoses across all races/ethnicities was made from 1982 to 1991. Median follow-up was 81 months and no collinearity was observed in the adjusted models. When examining cause-specific mortality and controlling for site and stage at diagnosis, gender, age and decade of diagnosis, the HR for non-Hispanic Black patients was lower than that for non-Hispanic White patients (HR 0.7; 95% confidence interval (CI): 0.6-0.8). However, when examining all-cause mortality, this difference disappeared (HR 1.1; 95% CI: 1.0-1.2). Stage at diagnosis impacted HR; patients diagnosed with distant metastases had significantly worse survival.When taking cause-specific mortality into consideration and after controlling for stage and site at diagnosis, gender, and age and decade of diagnosis, non-Hispanic Black patients had a lower HR compared to non-Hispanic White patients. However, this difference disappeared when examining all-cause mortality. Further research is needed to explore this finding and to determine what factors may be associated with late-stage melanoma diagnosis., Competing Interests: The authors have no conflicts of interest to disclose.

To investigate the relationship among parity, length of the inter-pregnancy intervals and excessive pregnancy weight gain in the first pregnancy and the risk of obesity. Using a prospective cohort study of 3,422 non-obese, non-pregnant US women aged 14-22 years at baseline, adjusted Cox models were used to estimate the association among parity, inter-pregnancy intervals, and excessive pregnancy weight gain in the first pregnancy and the relative hazard rate (HR) of obesity. Compared to nulliparous women, primiparous women with excessive pregnancy weight gain in the first pregnancy had a HR of obesity of 1.79 (95% CI 1.40, 2.29); no significant difference was seen between primiparous without excessive pregnancy weight gain in the first pregnancy and nulliparous women. Among women with the same pregnancy weight gain in the first pregnancy and the same number of inter-pregnancy intervals (12 and 18 months or ≥18 months), the HR of obesity increased 2.43-fold (95% CI 1.21, 4.89; p = 0.01) for every additional inter-pregnancy interval of <12 months; no significant association was seen for longer inter-pregnancy intervals. Among women with the same parity and inter-pregnancy interval pattern, women with excessive pregnancy weight gain in the first pregnancy had an HR of obesity 2.41 times higher (95% CI 1.81, 3.21; p < 0.001) than women without. Primiparous and nulliparous women had similar obesity risk unless the primiparous women had excessive pregnancy weight gain in the first pregnancy, then their risk of obesity was greater. Multiparous women with the same excessive pregnancy weight gain in the first pregnancy and at least one additional short inter-pregnancy interval had a significant risk of obesity after childbirth. Perinatal interventions that prevent excessive pregnancy weight gain in the first pregnancy or lengthen the inter-pregnancy interval are necessary for reducing maternal obesity.

Premise of the Study: Plant populations that face new environments adapt and diverge simultaneously, and both processes leave footprints in their genetic diversity. Arabidopsis lyrata is an excellent species for studying these processes. Pairs of populations and subspecies of A. lyrata represent different stages of divergence. These populations are also known to be locally adapted and display various stages of emerging reproductive isolation., Methods: We used nucleotide diversity data from 19 loci to estimate divergence times and levels of diversity among nine A. lyrata populations. Traditional distance-based methods and model-based clustering analysis were used to supplement pairwise coalescence-based analysis of divergence., Key Results: Estimated divergence times varied from 130,000 generations between North American and European subspecies to 39,000 generations between central European and Scandinavian populations. In concordance with previous studies, the highest level of diversity was found in Central Europe and the lowest in North America and a diverged Russian Karhumäki population. Local adaptation among Northern and central European populations has emerged during the last 39,000 generations. Populations that are reproductively isolated by prezygotic mechanisms have been separated for a longer time period of ∼70,000 generations but still have shared nucleotide polymorphism., Conclusions: In A. lyrata, reproductively isolated populations started to diverge ∼70,000 generations ago and more closely related, locally adapted populations have been separate lineages for ∼39,000 generations. However, based on the posterior distribution of divergence times, the processes leading to reproductive isolation and local adaptation are likely to temporally coincide.

This review examines published literature to answer 2 questions: 1) Are there racial-ethnic differences in excessive or inadequate gestational weight gain (GWG) and postpartum weight retention (PPWR)? and 2) Is there evidence that approaches to promote healthy weight during and after pregnancy should vary by race-ethnicity? We identified a limited number of articles that explicitly looked at racial-ethnic differences in either GWG or PPWR after controlling for relevant covariates. These studies suggest that black and Hispanic women are more likely to gain inadequately based on the Institute of Medicine's pregnancy weight gain guidelines compared to white women. Black women are more likely to retain considerable amounts of weight postpartum compared to both Hispanic and white mothers. Studies were inconclusive as to whether Hispanic women retained more or less weight postpartum, so more research is needed. Interventions to increase GWG were few and those designed to reduce GWG and PPWR showed mixed results. Future studies should address the methodological and conceptual limitations of prior research as well as investigate biological mechanisms and behavioral risk factors to determine the reasons for the racial-ethnic differences in pregnancy-related weight outcomes. Interventions would benefit from a mixed-methods approach that specifically identifies race-relevant barriers to weight management during and after pregnancy. Attention to the greater social context in which pregnancy-related weight exists is also needed.

Objectives: We investigated the relationship between childbirth and 5-year incidence of obesity., Methods: We performed a prospective analysis of data on 2923 nonobese, nonpregnant women aged 14 to 22 years from the 1979 National Longitudinal Survey of Youth Cohort, which was followed from 1980 to 1990. We used multivariable logistic regression analyses to determine the adjusted relative risk of obesity for mothers 5 years after childbirth compared with women who did not have children., Results: The 5-year incidence of obesity was 11.3 per 100 parous women, compared with 4.5 per 100 nulliparous women (relative risk [RR] = 3.5; 95% confidence interval [CI] = 2.4, 4.9; P < .001). The 5-year incidence of obesity was 8.6 for primiparous women (RR = 2.8; 95% CI = 1.5, 5.0) and 12.2 for multiparous women (RR = 3.8; 95% CI = 2.6, 5.6). Among parous women, White women had the lowest obesity incidence (9.1 per 100 vs 15.1 per 100 for African Americans and 12.5 per 100 for Hispanics)., Conclusions: Parous women have a higher incidence of obesity than do nulliparous women, and minority women have a higher incidence of parity-related obesity than do White women. Thus, efforts to reduce obesity should target postpartum women and minority women who give birth.

A total of 24 pilots viewed dynamic encounters between their own aircraft and an intruder aircraft on a 2-D cockpit display of traffic information (CDTI) and estimated the point and time of closest approach. A three-level alerting system provided a correct categorical estimate of the projected miss distance on 83% of the trials. The remaining 17% of alerts were equally divided between misses and false alarms, of large and small magnitude. Roughly half the pilots depended on automation to improve estimation of miss distance relative to the baseline pilots, who viewed identical trials without the aid of automated alerts. Moreover, they did so more on the more difficult traffic trials resulting in improved performance on the 83% correct automation trials without causing harm on the 17% automation-error trials, compared to the baseline group. The automated alerts appeared to lead pilots to inspect the raw data more closely. While assisting the accurate prediction of miss distance, the automation led to an underestimate of the time remaining until the point of closest approach. The results point to the benefits of even imperfect automation in the strategic alerts characteristic of the CDTI, at least as long as this reliability remains high (above 80%).

Context: African-American women are disproportionately affected by obesity and its related diseases. How psychological and psychosocial factors that affect this population differ across weight categories remains poorly understood., Purpose: To determine whether poor mental health and family functioning are associated with obesity in African-American women., Methods: African-American women patients aged 21-65 years were interviewed at three primary care centers. Four well-established assessment tools were used to measure general mental and physical health status, family functioning, depressive symptoms and anxiety levels. Demographics, health behaviors and family and personal histories of overweight were assessed., Results: Among 113 patients, after controlling for age and parity, obese women had significantly higher anxiety levels, poorer perception of their physical health, more often were overweight as a child, had overweight parents or siblings and experienced more psychosocial problems in their family growing up, compared to overweight and normal weight women., Conclusions: The observed findings of poor mental health, perception of physical health and family function in obese African-American women support a need for clinical attention and further study.

Objective: Since 1996, autologous hemopoietic stem cell transplantation (HSCT) has been used to treat severe rheumatoid arthritis (RA). To date, published reports have been individual cases or series containing small numbers. This study combined the worldwide experience in a single analysis., Methods: The Autoimmune Disease Databases of the European Group for Blood and Marrow Transplantation (EBMT) and the Autologous Blood and Marrow Transplant Registry (ABMTR) were used to identify patients with RA treated with autologous HSCT. Further information relating to patient and treatment-specific variables was obtained by questionnaire., Results: Seventy-six patients were registered from 15 centers. Seventy-three patients had received autologous HSCT, and in 3 patients hematopoietic stem cells (HSC) were mobilized but not transplanted. Transplanted patients (median age 42 yrs, 74% female, 86% rheumatoid factor positive) had been previously treated with a mean of 5 (range 2-9) disease modifying antirheumatic drugs (DMARD). Significant functional impairment was present, with a median Health Assessment Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score mean 2.39 (SD 0.58). The high dose treatment regimen was cyclophosphamide (CYC) alone in the majority of patients, mostly 200 mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient CYC with total body irradiation and ATG. One patient received fludarabine with ATG. Following treatment, one patient received bone marrow but the rest received chemotherapy and/or granulocyte colony-stimulating factor mobilized peripheral blood stem cells. The harvest was unmanipulated in 28 patients, the rest receiving some form of lymphocyte depletion, mostly through CD34+ selection. Median followup was 16 months (range 3-55). Responses were measured using the American College of Rheumatology (ACR) criteria. Forty-nine patients (67%) achieved at least ACR 50% response at some point following transplant. There was a significant reduction in the level of disability measured by the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for persistent or recurrent disease activity, which provided disease control in about half the cases. Response was significantly related to seronegative RA (p = 0.02) but not to duration of disease, number of previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the graft. There was no direct transplant related mortality, although one patient, treated with the BuCYC regimen, died 5 months post-transplant from infection and incidental non-small cell lung cancer., Conclusion: Autologous HSCT is a relatively safe form of salvage treatment in severe, resistant RA. In these open label studies significant responses were achieved in most patients, with over 50% achieving an ACR 50 or more response at 12 months. Although the procedure is not curative, recurrent or persistent disease activity may be subsequently controlled in some patients with DMARD. Clinical trials are necessary to develop this approach in patients with aggressive disease who have failed conventional treatment including anti-tumor necrosis factor agents.

The International Space Station (ISS) is the largest international cooperative science and technology project ever undertaken. Involving the United States, Russia, Japan, Canada and 10 ESA Member States, it is now rapidly becoming a reality in orbit, offering unprecedented access for research and applications under space conditions. Europe has invested heavily in this endeavour and plans to exploit that investment by a vigorous utilisation of the ISS for life and physical sciences research and applications, space science, Earth observation, space technology development, the promotion of commercial access to space, and the use of space for educational purposes. In recent years, ESA has engaged in an intensive promotional effort to encourage potential user communities to exploit the novel opportunities that the ISS offers. It has also made significant financial commitments to develop both multi-user facilities for life and physical sciences studies in the Columbus Laboratory, and observational and technology exposure instruments using the external Columbus mounting locations, as well as giving financial support to promote commercial and educational activities. ESA has now elaborated a European Strategy for the efficient utilisation of the ISS by European scientists and other users, which is being coordinated with the Agency's Member States contributing to the ISS Programme, and with the European Science Foundation (ESF). In cooperation with the European Commission, ESA is also fostering synergy with the European Commission's Framework Programmes in terms of shared R&D objectives. This article describes the plan that has been evolved to integrate all of these various elements.

On 15 September 2000 in Washington DC, the Multilateral Coordination Board (MCB), the highest-level cooperative body established by the Memoranda of Understanding (MOUs) pertaining to the International Space Station (ISS) Programme signed early in 1998 by NASA and each of the Cooperating Agencies designated by the other ISS Partners (i.e. the Russian Space Agency, ESA, the Government of Japan and the Canadian Space Agency), approved the Code of Conduct for International Space Station Crews. This document contains a set of standards agreed by all Partners to govern the conduct of ISS crew members, starting with the first expedition crew launched from Baikonur in Kazakhstan on 31 October 2000. These standards had been developed over the previous six months by teams of Agency officials, working in close consultation with the competent authorities of the Partner States.