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The Southern Europe regional outlook presents a comparative assessment of the historical development of the healthcare system, health politics, and selected health-related indicators for Cyprus, Greece, Italy, Portugal, and Spain. The politics of democratic consolidation has influenced the development of healthcare systems; in some periods, healthcare policies have been central to the institutional consolidation and legitimation of existing regimes, but they have also been negatively affected by the political, administrative, and financial shortcomings of these governments. All of these countries have witnessed late transitions from social insurance healthcare systems based on occupation (with fairly developed means-tested programs) to universal and mostly tax-financed national health services: Italy and Portugal made this shift in the 1970s, Spain and Greece in the 1980s, and Cyprus after 2000. As the chapter argues, the central issue in Southern Europe concerns expanding healthcare access in the context of economic vulnerability. According to indicators such as infant mortality, life expectancy, and declines in treatable mortality, health outcomes in Southern Europe are largely favorable, but austerity politics have taken their toll.

Huntington disease (HD) is a fatal neurodegenerative disease caused by a pathogenic expansion of a CAG repeat in the huntingtin (HTT) gene. There are no disease-modifying therapies for HD. Artificial microRNAs targeting HTT transcripts for degradation have shown preclinical promise and will soon enter human clinical trials. Here, we examine the tolerability and efficacy of non-selective HTT lowering with an AAV5 encoded miRNA targeting human HTT (AAV5-miHTT) in the humanized Hu128/21 mouse model of HD. We show that intrastriatal administration of AAV5-miHTT results in potent and sustained HTT suppression for at least 7 months post-injection. Importantly, non-selective suppression of huntingtin was generally tolerated, however high dose AAV5-miHTT did induce astrogliosis. We observed an improvement of select behavioural and modest neuropathological HD-like phenotypes in Hu128/21 mice, suggesting a potential therapeutic benefit of miRNA-mediated non-selective HTT lowering. Finally, we also observed that potent reduction of wild type HTT (wtHTT) in Hu21 control mice was tolerated up to 7 months post-injection but may induce impairment of motor coordination and striatal atrophy. Taken together, our data suggests that in the context of HD, the therapeutic benefits of mHTT reduction may outweigh the potentially detrimental effects of wtHTT loss following non-selective HTT lowering.

Africans and Afro-descendants in Argentina have a long tradition of organizing to resist all forms of oppression. This can be traced back to the 17th century with various forms of organizations including cofradias (religious brotherhoods or fraternal organizations), naciones (Afro-descendant social and cultural organizations), mutual aid societies, and military-based organizations in Río de la Plata, the region that would become Argentina and Uruguay. From the mid-19th to the early 20th centuries, as a part of the construction of the Argentine nation as European, white, and “civilized,” the myth of black disappearance was reified through discursive elimination and the cessation of collecting data on race or color in official records. The rise of Peronism in the 1940s would cause the return of race to public discourse, as large internal migrations of nonwhites from the interior of the country descended on major cities like Buenos Aires. The opponents of Perón, and his policies that embraced these poor migrants, mocked these individuals as cabecitas negras (derogatory term meaning “little black heads”), but they would open the possibility for a new reworking of a more inclusive Argentina. The new migrants represented a merging of categories of race and class, as these negros included Afro-Argentines who formed part of Perón’s constituency. The late 20th century would bring more direct challenges to black invisibility, with multiple new organizations and events centered on the experiences of the African diaspora in Argentina. One of the first organizations created after the return to democracy in Argentina was the Comité Argentino Latinoamericano contra el Apartheid (The Argentine Committee against Apartheid) in 1984. The example set by this organization, alongside inspiration from black liberation movements in the United States, Brazil, and on the African continent, would be a catalyst for the creation of numerous new black organizations for decades to come. Black organizing in Argentina found support in activist networks across the globe as well as across international organizations, which was reflected by the multicultural turn in Latin America during the 1990s. The era sparked the creation of significant legislation and activities due to pressure from local activists and the international community through organizations like the Inter-American Development Bank and the World Bank. One of the earliest conferences organized by Argentine black activists was the first Jornada de Cultura Negra (Black Culture Conference) in 1991. The National Institute Against Discrimination, Xenophobia, and Racism (INADI) was created in 1995 by the Argentine state to address the needs of marginalized populations in Argentine society. The late 1990s and early 2000s saw increased immigration of highly visible Africans and Afro-descendants from Latin America and Caribbean countries, which led to the creation of novel organizations to serve their specific needs. New conferences and events that provided opportunities for these diasporas to organize and interact, like the Semana de África (Africa Week), were also created. Along with the existing black communities in Argentina, these organizations contributed to new legislation officially recognizing Afro-descendant populations and condemning racism. Many of these legislative acts were passed under the Fernández de Kirchner administration (2007–2015), like the 2015 Law No. 5.261 Against Discrimination, which provided a more comprehensive antidiscrimination policy, and the historic 2010 Argentine census which restored the possibility of identifying as Afro-descendant. The reappearance of the category in the 2010 census after over a 120-year absence had been prompted by the World Bank’s landmark census 5 years prior. Though these gains were primarily symbolic, they helped fortify black activism. Grassroots organizing and political mobilization has remained steadfast in spite of shifts in national politics, continuous economic instability, and increased antiblack racism at both the systemic and individual levels. As black activism increased incrementally over the decades, it inspired an upsurge of academic studies that in turn provided knowledge which helped propel activist efforts. The 21st century has been a particularly fruitful time in the Argentine academy as anthropological studies on Africans and Afro-descendants have proliferated. This time period has also marked a much-needed expansion of black organizing into more rural areas of the country, especially the northwest, which has historically had a large population of African descent. By holding more activities in the provinces and outside of the City of Buenos Aires, the decentralization of black activism has helped increase consciousness across the nation.

Objective Partial foot amputation is often associated with decreased mobility and function. Recent advances in custom carbon-fiber dynamic ankle-foot orthoses (CDOs) have improved gait, pain, and function following musculoskeletal trauma and can benefit individuals with partial foot amputation. However, limited information is available related to CDO use outside the military. The purpose of this case report is to describe the course of care and outcomes of a civilian provided with CDOs after bilateral transmetatarsal amputation. Case Description A 72-year-old man had a blood-borne bacterial infection (septicemia) of unknown origin at 68 years of age, developed limb-threatening necrosis of the hands and feet, and received bilateral transmetatarsal amputations with skin grafting. The patient initially used foam toe fillers and cushioned shoes but was functionally limited and experienced recurrent ulceration. He was fitted with bilateral CDOs 39 months after amputation and completed device-specific training with a physical therapist. Results After 1 week with the CDOs, ankle range of motion during gait was reduced, but greater than 40% increases were observed in bilateral ankle plantarflexor moments and ankle plantarflexion push-off power compared with the toe fillers. With additional therapist-directed training focused on gait and activity performance, ankle plantarflexor moments and plantarflexion push-off power further increased when compared with results after 1 week of CDO use. The patient reported marked improvement in quality of life with the CDOs due to improved walking ability on level and uneven terrain, marked improvement in confidence, and reduced pain. Conclusion This case reflects the lessons learned and outcomes of a civilian using bilateral CDOs after bilateral transmetatarsal amputation and with poor skin quality. The results from this case study suggest that carbon-fiber CDOs and focused training by a physical therapist can result in improved gait biomechanics, mobility, and quality of life.

Highlight Grapevine red blotch interferes with the hormonal and transcriptional regulation of berry development, leading to suppression of secondary metabolism and induction of photosynthesis at late ripening stages., Grapevine red blotch-associated virus (GRBaV) is a major threat to the wine industry in the USA. GRBaV infections (aka red blotch disease) compromise crop yield and berry chemical composition, affecting the flavor and aroma properties of must and wine. In this study, we combined genome-wide transcriptional profiling with targeted metabolite analyses and biochemical assays to characterize the impact of the disease on red-skinned berry ripening and metabolism. Using naturally infected berries collected from two vineyards, we were able to identify consistent berry responses to GRBaV across different environmental and cultural conditions. Specific alterations of both primary and secondary metabolism occurred in GRBaV-infected berries during ripening. Notably, GRBaV infections of post-véraison berries resulted in the induction of primary metabolic pathways normally associated with early berry development (e.g. thylakoid electron transfer and the Calvin cycle), while inhibiting ripening-associated pathways, such as a reduced metabolic flux in the central and peripheral phenylpropanoid pathways. We show that this metabolic reprogramming correlates with perturbations at multiple regulatory levels of berry development. Red blotch caused the abnormal expression of transcription factors (e.g. NACs, MYBs, and AP2-ERFs) and elements of the post-transcriptional machinery that function during red-skinned berry ripening. Abscisic acid, ethylene, and auxin pathways, which control both the initiation of ripening and stress responses, were also compromised. We conclude that GRBaV infections disrupt normal berry development and stress responses by altering transcription factors and hormone networks, which result in the inhibition of ripening pathways involved in the generation of color, flavor, and aroma compounds.

Physiology and ecology are intimately linked; thus, ecological observations can be strengthened by an understanding of organismal physiology. Through a symposium entitled “Applications of Physiological Ecology in Elasmobranch Research” at the 2017 American Elasmobranch Society meeting, we demonstrated the strengths of collaborative efforts across disciplines for informing conservation efforts., A strength of physiological ecology is its incorporation of aspects of both species’ ecology and physiology; this holistic approach is needed to address current and future anthropogenic stressors affecting elasmobranch fishes that range from overexploitation to the effects of climate change. For example, physiology is one of several key determinants of an organism’s ecological niche (along with evolutionary constraints and ecological interactions). The fundamental role of physiology in niche determination led to the development of the field of physiological ecology. This approach considers physiological mechanisms in the context of the environment to understand mechanistic variations that beget ecological trends. Physiological ecology, as an integrative discipline, has recently experienced a resurgence with respect to conservation applications, largely in conjunction with technological advances that extended physiological work from the lab into the natural world. This is of critical importance for species such as elasmobranchs (sharks, skates and rays), which are an especially understudied and threatened group of vertebrates. In 2017, at the American Elasmobranch Society meeting in Austin, Texas, the symposium entitled `Applications of Physiological Ecology in Elasmobranch Research’ provided a platform for researchers to showcase work in which ecological questions were examined through a physiological lens. Here, we highlight the research presented at this symposium, which emphasized the strength of linking physiological tools with ecological questions. We also demonstrate the applicability of using physiological ecology research as a method to approach conservation issues, and advocate for a more available framework whereby results are more easily accessible for their implementation into management practices.

Background and aims Coastal plant communities globally are highly vulnerable to future sea-level rise and storm damage, but the extent to which these habitats are affected by the various environmental perturbations associated with chronic salinization remains unclear. In this study, we examine the relationship between North Carolina wetland tree community composition and basal area change and indicators of salinization such as soil salt ion content and elevation. Methods We surveyed 34 forest plots in forested, freshwater wetlands across the Albemarle-Pamlico Peninsula. A subset of our study sites had been sampled during the previous decade as part of the Carolina Vegetation Survey, enabling us to investigate the environmental effects on current community structure, and community change over time. Key results Multi-variate (ordination) analysis and linear regression models of tree community composition revealed that elevation and soil salt content were correlated with changes in total site tree basal area. Shifts in tree community composition were, however, only weakly correlated with indicators of salinization, specifically elevation, soil sulphate and sodium, but not chloride. While the majority of plots experienced gains in basal area over the past decade, consistent with secondary succession, sites with high soil salt content or low elevation experienced basal area (biomass) loss during the same period. Conclusions The key factors associated with chronic saltwater intrusion (soil ion content) likely explain recent changes in tree biomass, and potential shifts in community composition in low-elevation sites along the North Carolina coast. Not only is it probable that other coastal forest ecosystems worldwide will experience similar stressors and shifts in community biomass and structure as sea levels rise, but the ability of these habitats to deliver key ecosystem services like carbon sequestration and flood defence will be compromised as a result.

Neuroprogressive processes in major depressive disorder (MDD) can occur in association with recurrent episodes. The primary biological underpinnings are mediated by increases in the levels of immune-inflammation, tryptophan catabolites, mitochondrial dysfunction, and oxidative and nitrosative stress. Such biochemical alterations may be driven by changes in many peripheral and central sites, including in the gut, as well as by early developmental priming, such as prenatal stressors and breastfeeding consequences. As such, the conceptualization of MDD is shifted from simple psychological and central biochemical models to one that includes whole body processes over a developmental timescale. This provides a model that better integrates wider bodies of data relevant to the aetiology and course of MDD, and which therefore underpins the neuroprogressive processes that can occur over the course of MDD. This also significantly challenges current MDD (and wider psychiatric) classification by shifting classification to one based on biological processes rather than one based on subjective phenomenology.

Faculty will focus on the biology of aging as a contributor to the vulnerability in COVID-19. Faculty will present the latest concepts and insights that will advance our ability to confront this global outbreak. Our goal for this session is to connect with the concept of Geroscience and how ideas from aging biology research can be incorporated to improve outcomes and informed practice. Although the emphasis is on biology, the goal is to provide insight in a manner that is readily accessible to researchers across the aging spectrum that they might translate these ideas in the face of a very real-world challenge.

A high seroprevalence of hepatitis A virus (81%) among human immunodeficiency virus–negative high-risk men who have sex with men is likely why this community was largely spared from a recent hepatitis A virus outbreak in San Diego, California.

Calorie restriction without malnutrition increases longevity and delays the onset of age-associated disorders in multiple species. Recently, greater emphasis has been placed on healthy life span and preventing frailty than on longevity. Here, we show the beneficial effect of long-term calorie restriction on frailty in later life in a nonhuman primate. Frail phenotypes were evaluated using metabolic and physical activity data and defined using the Fried index. Shrinking was defined as unintentional weight loss of greater than 5% of body weight. Weakness was indicated by decline in high intensity spontaneous physical activity. Poor endurance or exhaustion was indicated by a reduction in energy efficiency of movements. Slowness was indicated by physical activity counts in the morning. Low physical activity level was measured by total energy expenditure using doubly labeled water divided by sleeping metabolic rate. Weakness, poor endurance, slowness, and low physical activity level were significantly higher in control compared with calorie restriction (p < .05) as was total incidence of frailty (p < .001). In conclusion, we established a novel set of measurable criteria of frailty in nonhuman primates, and using these criteria, showed that calorie restriction reduces the incidence of frailty and increases healthy life span in nonhuman primates.

Background: Genes involved in the complement pathway of the innate immune system have been implicated in risk for schizophrenia. Emerging evidence suggests that this pathway is involved in synaptic pruning, a phenomenon that likely influences cortical thinning and may underlie reduction of cortical thickness in prefrontal regions in schizophrenia. However, a link between complement genes and cortical thickness has not yet been established in humans.

Author(s): Anderson, Albert M; Munoz-Moreno, Jose A; McClernon, Daniel R; Ellis, Ronald J; Cookson, Debra; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Sacktor, Ned; Simpson, David M; Franklin, Donald R; Heaton, Robert K; Grant, Igor; Letendre, Scott L; CHARTER Group | Abstract: Background Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).Methods Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.Results HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4+ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P l .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P l .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.Conclusions Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4+ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.

Background: Most women with ductal carcinoma in situ (DCIS) will receive breast-conserving surgery (BCS) and radiation (RT). RT can be omitted for women at low risk of local recurrence (LR). The Oncotype DX DCIS score (DS) predicts LR risk after BCS alone. This study assesses the impact of RT and DS on LR risk. Methods: Population-based cohort analysis of individuals with DCIS treated by BCS ± RT from 1994–2003. Treatment and outcomes were determined by linkage and chart review. We used a propensity score–adjusted multivariable model to examine associations between DS and LR and evaluate the impact of RT. All statistical tests were two-sided. Results: The cohort includes 571 individuals treated by BCS alone, 689 cases treated with BCS + RT. Median follow-up was 9.4 years. On multivariable analysis, factors associated with LR include RT, age at diagnosis, tumor size, and multifocality. Adjusting for these factors, the DS risk group was statistically significantly associated with LR risk (hazard ratio high/intermediate = 1.75, 95% confidence interval = 1.28 to 2.41, P < .001). Women with a low-risk DS treated by BCS alone had an LR risk of 10.6% at 10 years and a small benefit from RT, while those with a high DS had a higher risk of LR (25.4%) after BCS alone and greater benefit from RT. A subgroup of patients with favorable clinicopathological features had a high-risk DS; these patients had a higher than expected risk of LR after BCS alone and a greater benefit with RT. Conclusions: The DS molecular assay improves risk stratification and estimates of RT benefit in individuals with DCIS treated with breast-conserving therapy.

Nutrient response pathways are conserved modifiers of longevity, and dietary restriction is the most studied intervention for slowing aging in laboratory animals. For many years it was believed that lifespan extension from dietary restriction was tightly linked to total caloric intake. Recent evidence suggests that the interaction between diet and aging is more complex than this, however, with nutrient sensing, dietary composition, and circadian components all playing a role. This symposium will delve into some of the complex biological interactions linking food intake, lifespan, and diseases of aging.

Skeletal muscle, in addition to being comprised of a heterogeneous muscle fiber population, also includes extracellular components that do not contribute to positive tensional force production. Here we test segmental bioelectrical impedance spectroscopy (S-BIS) to assess muscle intracellular mass and composition. S-BIS can evaluate electrical properties that may be related to muscle force production. Muscle fiber membranes separate the intracellular components from the extracellular environment and consist of lipid bilayers which act as an electrical capacitor. We found that S-BIS measures accounted for ~85% of the age-related decrease in appendicular muscle power compared with only ~49% for dual-energy x-ray absorptiometry (DXA) measures. Indices of extracellular (noncontractile) and cellular (contractile) compartments in skeletal muscle tissues were determined using the Cole-Cole plot from S-BIS measures. Characteristic frequency, membrane capacitance, and phase angle determined by Cole-Cole analysis together presented a S-BIS complex model that explained ~79% of interindividual variance of leg muscle power. This finding underscores the value of S-BIS to measure muscle composition rather than lean mass as measured by DXA and suggests that S-BIS should be highly informative in skeletal muscle physiology.

Identifying client characteristics that influence negative psychotherapy outcomes is vitally important. This chapter reviews baseline client characteristics that have demonstrated direct relationships with unsuccessful treatment outcomes, as well as client traits that have functioned as moderators of specific treatment effects and process-outcome associations. Throughout this chapter client characteristics are defined as preexisting individual differences or traits that clients bring into the therapy context. Identifying client baseline characteristics that influence, directly or indirectlyc, negative outcomes is vitally important. This review divides such client characteristics into the following categories: demographic variables, expectancies, mental health variables, intra-psychic traits, and interpersonal traits. Implications of reviewed research findings for psychotherapy practice are discussed.

Background Antimicrobial resistance is one of the most serious threats to public health. Antimicrobial stewardship initiatives have begun to expand from acute care to ambulatory care settings. While many programs have demonstrated pharmacist-led stewardship successes in inpatient and emergency department (ED) settings, there is a paucity of literature exploring these initiatives in urgent care (UC) sites. This study aimed to determine the impact of implementing a pharmacist-led antimicrobial stewardship program (ASP) in the UC setting. Methods A retrospective quasi-experimental study was conducted evaluating patients from two health system-affiliated UC sites with positive urine or wound culture results following discharge. In April 2015, the health system’s infectious diseases and ED pharmacists, with support from UC providers, implemented empiric therapy guidelines and a collaborative practice agreement allowing for pharmacist-led culture follow-up via a stewardship-focused protocol. The primary outcome of this study was to compare guideline-concordant antibiotic prescribing (defined as the combination of appropriate agent, dose, and duration of therapy) between the pre-ASP and post-ASP groups. Secondary outcomes included comparing the number of patients who required follow-up, time to follow-up, UC or ED revisits within 72 hours, and hospital admission within 30 days between groups. Results Three hundred patients were included in the study (pre-ASP n = 150, post-ASP n = 150). Total guideline-concordant prescribing for all diagnoses was significantly improved in the post-ASP group compared with the pre-ASP group (41.3% vs. 53.3%, P = 0.037). Guideline-concordant antibiotic selection improved in the post-ASP group (51% vs. 68%, P = 0.01) while dose (70 % vs. 74%, P = 0.287) and duration (61% vs. 65%, P = 0.283) were similar between groups. Follow-up was required for 27 (18%) patients in the pre-ASP group vs. 16 (10.7%) in the post-ASP group (P = 0.07), however median time to follow-up call was longer in the post-ASP group (71 vs. 38 hours, P < 0.001). There were no differences between groups in UC (P = 1.0) and ED revisits (P = 1.0) within 72 hours or hospital admissions within 30 days (P = 0.723). Conclusion A pharmacist-led urgent care ASP was associated with significantly improved guideline-concordant antimicrobial prescribing. Disclosures All authors: No reported disclosures.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.

Temporal changes in the in situ germination flux of cysts and the abundance of vegetative cells of the toxic dinoflagellate Alexandrium catenella were investigated in Ago Bay, central Japan from July 2003 to December 2004. The in situ germination flux (cells m−2 day−1) was measured using ‘plankton emergence trap/chambers (PET chambers)’. Germination of the cysts in the sediments occurred continuously during the study, ranging from 52 to 1753 cells m−2 day−1, with no temporal trend. This germination pattern appeared to be promoted by a short mandatory dormancy period for newly formed cysts coupled with a broad temperature window for germination. For the vegetative populations, high abundances (>105 cells m−2) were recorded in the water column from spring to summer and from autumn to early winter. The size of the vegetative populations did not correlate with the cyst germination flux but rather larger vegetative populations were often observed when the water temperature was around 20°C, indicating that bloom development was mainly regulated by the temperature. Nonetheless, the continuous germination pattern of A. catenella is advantageous enabling the germinated cells to immediately exploit favorable bloom conditions.

Testicular toxicity is an important safety endpoint in drug development and risk assessment, but reliable and translatable biomarkers for predicting injury have eluded researchers. However, this area shows great potential for improvement, with several avenues currently being pursued. This was the topic of a symposium session during the 2013 Society of Toxicology Annual Meeting in San Antonio, TX, entitled “Translatable Indicators of Testicular Toxicity: Inhibin B, MicroRNAs, and Sperm Signatures.” This symposium brought together stakeholders from academia, government, and industry to present the limitations and drawbacks of currently used indicators of injury and discussed the ongoing efforts in developing more predictive biomarkers of injury. The presentations highlighted the early challenges of using circulating inhibin B and microRNA levels, and sperm messenger RNA transcript abundance and DNA methylation profiles, as novel biomarkers of testicular toxicity.

Background Based on preclinical studies, the vascular endothelial pathway is an important mechanism for estrogen receptor resistance. We conducted a phase II study of fulvestrant and bevacizumab in patients with aromatase inhibitor pretreated metastatic breast cancer. Patients and methods A single-stage phase II study was conducted with these objectives: 6-month progression-free survival (PFS), tumor response, toxic effect, and overall survival. Regimen: 250 mg fulvestrant days 1 and 15 (cycle 1) then day 1 (cycle 2 and beyond) and 10 mg/kg bevacizumab days 1 and 15 of each 4-week cycle. Results At interim analysis, 20 eligible patients initiated treatment, 11 were progression free and on treatment at 3 months, not meeting the protocol-specified efficacy requirements (at least 12 of 20). Accrual remained open during interim analysis with 36 patients enrolling before final study closure. Among the 33 eligible patients, the median PFS was 6.2 months [95% confidence interval (CI) 3.6–10.1 months]. Of the 18 with measurable disease, 4 (22%) patients (95% CI 6% to 48%) had a confirmed tumor response (1 complete, 3 partial). The most common grade 3/4 adverse events were hypertension 3 (9%) and headache 3 (9%). Conclusions The fulvestrant/bevacizumab combination is safe and tolerable; however, it did not meet its statistical end point.

In the centuries immediately preceding the twentieth two main attitudes to the study of case, simplifying somewhat, can be differentiated. On the one hand, there was reasserted, particularly in the nineteenth century, a view of case as a purely morphological phenomenon (reverting to prevalent conceptions in the ancient world). The subtypes of case inflections came to be characterised by the functions they signalled, with a major division being made between ‘syntactic cases’ and ‘local’. This article deals with case in localist case grammar and discusses syntactic derivationality, which is superfluous in a framework that has available to it the expressibility made accessible by an implementation, along with dependency structures that permit restricted argument-sharing, of the traditional insights concerning ‘case’. Hence, semantic relations are basic to both the lexicon and the syntax, and morphology is only one expression-variant for ‘case’ or semantic relations.

Colloquially, “education” usually means “schooling,” and thus this bibliography focuses on schooling, but it also considers education more broadly defined. Sections on schooling are limited to pre-primary, primary, and secondary education, excluding postsecondary even though some university students arguably fall on the border between childhood and adulthood. The interdisciplinary field of educational studies is largely an applied field and much of its literature is devoted to efforts to improve schooling; however, this bibliography identifies descriptive studies of actual practices and beliefs rather than prescriptions for reform. An important theme of literature identified here is that schooling has recently become among the most important settings in which children live and develop, meaning that the current global form of schooling as well as variations in schooling “on the ground” have huge consequences for children’s lives and powerful meanings for all of us.

Reasoning often occurs under emotionally charged, opinion-laden circumstances. The belief-bias effect indexes the extent to which reasoning is based upon beliefs rather than logical structure. We examined whether emotional content increases this effect, particularly for adults genetically predisposed to be more emotionally reactive. SS/SL(G) carriers of the serotonin transporter genotype (5-HTTLPR) were less accurate selectively for evaluating emotional relational reasoning problems with belief-logic conflict relative to L(A)L(A) carriers. Trait anxiety was positively associated with emotional belief-bias, and the 5-HTTLPR genotype significantly accounted for the variance in this association. Thus, deductive reasoning, a higher cognitive ability, is sensitive to differences in emotionality rooted in serotonin neurotransmitter function.