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White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.
Recent theoretical models have posited that increases in self-injurious thoughts and behaviors (SITBs) during adolescence may be linked to failures in biological stress regulation in contexts of social stress. However, there is a lack of data examining this hypothesis during the transition to adolescence, a sensitive period of development characterized by changes across socioaffective and psychophysiological domains. Building on principles from developmental psychopathology and the RDoC framework, the present study used a longitudinal design in a sample of 147 adolescents to test whether interactions among experiences of social (i.e., parent and peer) conflict and cardiac arousal (i.e., resting heart rate) predicted adolescents’ engagement in SITBs (i.e., nonsuicidal self-injury, NSSI; and suicidal ideation; SI) across 1-year follow-up. Prospective analyses revealed that adolescents experiencing a combination of greater peer, but not family, conflict and higher cardiac arousal at baseline showed significant longitudinal increases in NSSI. In contrast, social conflict did not interact with cardiac arousal to predict future SI. Findings indicate that greater peer-related interpersonal stress in adolescents may increase risk for future NSSI among youth with physiological vulnerabilities (i.e., higher resting heart rate) that may be markers of maladaptive stress responses. Future research should examine these processes at finer timescales to elucidate whether these factors are proximal predictors of within-day SITBs.
Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR).
In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview.
At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment.
ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.
The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking.
A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene–environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables.
At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR.
No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.
Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.
In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.
There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.
In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.
To evaluate the impact of a pharmacist-driven Staphylococcus aureus bacteremia (SAB) safety bundle supported by leadership and to compare compliance before and after implementation.
Retrospective cohort study with descriptive and before-and-after analyses.
Tertiary-care academic medical center.
All patients with documented SAB, regardless of the source of infection, were included. Patients transitioned to palliative care were excluded from before-and-after analysis.
A pharmacist-driven safety bundle including documented clearance of bacteremia, echocardiography, removal of central venous catheters, and targeted intravenous therapy of at least 2 weeks duration was implemented in November 2015 and was supported by leadership with stepwise escalation for nonresponse. A descriptive analysis of all patients with SAB during the study period included pharmacy interventions, acceptance rates, and escalation rates. A pre–post implementation analysis of 100 sequential patients compared bundle compliance and descriptive parameters.
Overall, 391 interventions were made in the 20-month period following implementation, including 20 “good saves” avoiding potentially major adverse events. No statistically significant differences in complete bundle compliance were detected between the periods (74% vs 84%; P = .08). However, we detected a significant increase in echocardiography after the bundle was implemented (83% vs 94%; P = .02) and fewer patients received suboptimal definitive therapy after the bundle was implemented (10% vs 3%; P = .045).
This pharmacist-driven SAB safety bundle with leadership support showed improvement in process measures, which may have prevented major adverse events, even with available infectious diseases (ID) consultation. It provides a critical safety net for institutions without mandatory ID consultation or with limited antimicrobial stewardship resources.
Constitutional drafters often look to foreign constitutional models, ideas, and texts for inspiration; many are explicit about their foreign borrowing. However, when implemented domestically, the meaning of borrowed elements often changes. Political scientists and scholars of comparative constitutional law have analyzed the transnational movement of constitutional ideas and norms, but the political processes through which the meaning of foreign provisions might be refashioned remain understudied. Sociolegal scholars have examined the “transplantation” and “translation” of laws and legal institutions, but they rarely scrutinize this process in the context of constitutions. Drawing on an examination of borrowed constitutional elements in four cases (Pakistan, Morocco, Egypt, Israel), this article builds on research in comparative politics, comparative constitutional law, and sociolegal studies to provide a nuanced picture of deliberate efforts to import “inclusive” constitutional provisions regarding religion-state relations while, at the same time, refashioning the meaning of those provisions in ways that “exclude” specific forms of religious, sectarian, doctrinal, or ideological diversity. Building on sociolegal studies regarding the translation of law, we argue that foreign constitutional elements embraced by politically embedded actors are often treated as “empty signifiers” with meanings that are deliberately transformed. Tracing the processes that lead political actors to engage foreign constitutional elements, even if they have no intention of transplanting their prior meaning, we highlight the need for detailed case studies to reveal both the international and the national dynamics that shape and reshape the meaning of constitutions today.
Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.
The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).
Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.
Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.
Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis.
The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews.
In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing.
Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.
Antimicrobial stewardship improves patient care and reduces antimicrobial resistance, inappropriate use, and adverse outcomes. Despite high-profile mandates for antimicrobial stewardship programs across the healthcare continuum, descriptive data, and recommendations for dedicated resources, including appropriate physician, pharmacist, data analytics, and administrative staffing support, are not robust. This review summarizes the current literature on antimicrobial stewardship staffing and calls for the development of minimum staffing recommendations.
Building on current research regarding constitutional migration, this article shows how constitutional provisions protecting religious freedom (“subject to public order”) arrived in the Islamic Republic of Pakistan, not via colonial British or traditional Islamic sources—both explicitly rejected—but via deliberate constitutional borrowing from “anti-colonial” precursors in Ireland and, especially, India. Drawing on Ernesto Laclau's notion of “empty signifiers,” the article highlights the shifting political circumstances that transformed the meaning of Pakistan's borrowed constitutional provisions. Even as core texts guaranteeing an individual's right to peaceful religious practice were imported, political, legal, and conceptual modulations ensured that specific forms of peaceful religious practice were refashioned as a source of religious provocation and, therein, public disorder. Far from protecting religious freedom, this repurposing of imported constitutional clauses tied to “the politics of public order” underpinned the formal legal restriction of an otherwise explicit right.
In both India and Pakistan, parliament is constitutionally endowed with ‘constituent power’, that is, the power to introduce constitutional amendments via procedures laid down in the constitution itself. Duly promulgated amendments, however, are occasionally struck down when Supreme Court judges see them as violating what the judges themselves define as the ‘essential features’ of each country’s constitutional ‘basic structure’. I trace the migration of basic structure jurisprudence from India to Pakistan, focusing on the ways in which it has elevated the power of judges over that of elected officials in the realm of religion-state relations. Specifically, I highlight the ways in which judicial independence vis-à-vis judicial appointments has been described as an essential feature of each country’s constitution, greatly enhancing the autonomous power of judges to mould constitutional benches that, in turn, define India’s constitutional understanding of secularism and Pakistan’s relationship with Islam.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.