Passive Immunotherapy in Alzheimer’s Disease

The development of therapeutics for the treatment of Alzheimer’s disease (AD) has been challenged with a myriad of obstacles: an evolving and incomplete understanding of disease etiology and progression, challenges with early diagnosis, multifactorial genetic and environmental factors that contribute to patient variability, and the cost of conducting lengthy clinical trials. One approach that has garnered a significant amount of attention and resources for its potential as a disease modifying approach is passive immunotherapy directed at clearing amyloid-β (Aβ) species, a pathological hallmark of Alzheimer’s disease. While passive immunotherapeutic trials directed at Aβ have not yet demonstrated clinical benefit, they have prompted important advances in the application and understanding of biomarkers, patient selection, novel functional readouts, and safety monitoring. Application of these lessons has enabled more recent clinical trials to incorporate better trial designs and refine inclusion criteria to optimize patient population enrollment. In addition, new passive immunotherapy targets emerging in the clinic have emerged, as well as novel technologies to enhance future antibody therapeutics. Taken together, the advances in research and clinical science have prepared the passive immunotherapy field to advance emerging promising disease modifying treatments in AD

Optical properties of a single-colour centre in diamond with a green zero-phonon line

We report the photoluminescence characteristics of a colour centre in diamond grown by plasma-assisted chemical vapour deposition. The colour centre emits with a sharp zero-phonon line at 2.330 eV (λ=532 nm) and a lifetime of 3.3 ns, thus offering potential for a high-speed single-photon source with green emission. It displays a vibronic emission spectrum with a Huang–Rhys parameter of 2.48 at 77 K. Hanbury–Brown and Twiss measurements reveal that the electronic level structure of the defect includes a metastable state that can be populated from the optically excited state

P1NP and β-CTX-1 responses to a prolonged, continuous running bout in young healthy adult males: a systematic review with individual participant data meta-analysis.

Circulating biomarkers of bone formation and resorption are widely used in exercise metabolism research, but their responses to exercise are not clear. To quantify group responses and inter-individual variability of P1NP and β-CTX-1 after prolonged, continuous running (60-120 min at 65-75% VO2max) in young healthy adult males using individual participant data (IPD) meta-analysis. The protocol was designed following PRISMA-IPD guidelines. Changes in P1NP and β-CTX-1 relative to baseline were measured during, immediately after, and in the hours and days following exercise. Typical hourly and daily variations were estimated from P1NP and β-CTX-1 changes relative to baseline in non-exercise (control) conditions. Group responses and inter-individual variability were quantified with estimates of the mean and standard deviation of the difference, and the proportion of participants exhibiting an increased response. Models were conducted within a Bayesian framework with random intercepts to account for systematic variation across studies. P1NP levels increased during and immediately after running, where the proportion of response was close to 100% (75% CrI: 99 to 100%). P1NP levels returned to baseline levels within 1 hour and over the next 4 days, showing comparable mean and standard deviation of the difference with typical hourly (0.1 ± 7.6 ng·ml-1) and daily (-0.4 ± 5.7 ng·ml-1) variation values. β-CTX-1 levels decreased during and up to 4 hours after running with distributions comparable to typical hourly variation (-0.13 ± 0.11 ng·ml-1). There was no evidence of changes in β-CTX-1 levels during the 4 days after the running bout, where distributions were also similar between the running data and typical daily variation and (-0.03 ± 0.10 ng·ml-1). Transient increases in P1NP were likely biological artefacts (e.g., connective tissue leakage) and not reflective of bone formation. Comparable small decreases in β-CTX-1 identified in both control and running data, suggested that these changes were due to the markers' circadian rhythm and not the running intervention. Hence, prolonged continuous treadmill running did not elicit bone responses, as determined by P1NP and β-CTX-1, in this population. The protocol for this review was pre-registered on the Open Science Framework prior to implementation (https://osf.io/y69nd)

What voters want: reactions to candidate characteristics in a survey experiment

There has been extensive research into the extent to which voters utilise short cuts based on gender and race stereotypes when evaluating candidates, but relatively little is known about how they respond to other background characteristics. We compare the impact of candidates' sex, religion, age, education, occupation and location/residence through a survey experiment in which respondents rate two candidates based on short biographies. We find small differences in the ratings of candidates in response to sex, religion, age and education cues but more sizeable effects are apparent for the candidate's occupation and place of residence. Even once we introduce a control for political party into our experimental scenarios the effect of candidate's place of residence continues to have a sizeable impact on candidate evaluations. Our research suggests that students of electoral behaviour should pay attention to a wider range of candidate cues

What is a sustainable healthy diet? A discussion paper

The food system today is destroying the environment upon which future food production depends. While the food system generates enough food energy for our population of over 7 billion it does not deliver adequate and affordable nutrition for all. About half the global population is inadequately or inappropriately nourished. Without action, these problems are set to become acute. As our global population grows, urbanises and becomes wealthier, it is demanding more resource intensive, energy rich foods. What, and how much we eat directly affects what, and how much is produced. We therefore need to consume more „sustainable diets‟ – diets that have lower environmental impacts, and are healthier. But what does such a diet look like? Can health, environmental sustainability, and all the other goals we have for our food system really be reconciled, or will there be trade offs

Abdominal Wall Transplantation: Indications and Outcomes

Abstract Purpose of Review This article aims to review published outcomes associated with full-thickness vascularized abdominal wall transplantation, with particular emphasis on advances in the field in the last 3 years. Recent Findings Forty-six full-thickness vascularized abdominal wall transplants have been performed in 44 patients worldwide. Approximately 35% of abdominal wall transplant recipients will experience at least one episode of acute rejection in the first year after transplant, compared with rejection rates of 87.8% and 72.7% for hand and face transplant respectively. Recent evidence suggests that combining a skin containing abdominal wall transplant with an intestinal transplant does not appear to increase sensitization or de novo donor-specific antibody formation. Summary Published data suggests that abdominal wall transplantation is an effective safe solution to achieve primary closure of the abdomen after intestinal or multivisceral transplant. However, better data is needed to confirm observations made and to determine long-term outcomes, requiring standardized data collection and reporting and collaboration between the small number of active transplant centres around the worl

Adapting effects of emotional expression in anxiety: evidence for an enhanced late positive potential

An adaptation paradigm was used to investigate the influence of a previously experienced visual context on the interpretation of ambiguous emotional expressions. Affective classification of fear-neutral ambiguous expressions was performed following repeated exposure to either fearful or neutral faces. There was a shift in the behavioural classification of morphs towards ‘fear’ following adaptation to neutral compared to adaptation to fear with a non-significant trend towards the high anxiety group compared to the low being more influenced by the context. The event-related potential (ERP) data revealed a more pronounced late positive potential (LPP), beginning at ~400 ms post-stimulus onset, in the high but not the low anxiety group following adaptation to neutral compared to fear. In addition, as the size of the behavioural adaptation increased there was a linear increase in the magnitude of the late-LPP. However, context-sensitivity effects are not restricted to trait anxiety, with similar effects observed with state anxiety and depression. These data support the proposal that negative moods are associated with increased sensitivity to visual contextual influences from top-down elaborative modulations, as reflected in an enhanced late positive potential deflection

Language and reading impairments are associated with increased prevalence of non-right handedness

Funding: Royal Society - UF150663, RGF\EA\180141; Wellcome Trust - 217065/Z/19/Z; H2020 European Research Council - 694189; NWO - 451-15-017; National Health and Medical Research Council - 1173896; Canadian Institute for Health Research - MOP-133440.Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.Publisher PDFPeer reviewe