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As COVID-19 spread rapidly during the early months of the pandemic, many communities around the globe anxiously waited for a vaccine. At the start of the pandemic, it was widely believed that Africa would be a significant source of infection, and thus, vaccinating African communities became a primary goal among local and global health authorities. However, when the COVID-19 vaccine became available in March 2021 in Sierra Leone, many people viewed it with scepticism and hesitation. While much literature has focused on access and distribution-related challenges for vaccination in the region, a growing number of studies discuss vaccine hesitancy as driving low vaccine uptake. Shifting attention to understanding the determinants of vaccine hesitancy remains fundamental to increasing vaccination rates, as negative vaccine perceptions tend to delay or prevent vaccination. This study sought to do this by assessing, through semi-structured qualitative interviews, vaccine-related attitudes and experiences of residents of Sierra Leone’s Kono District. In contrast to studies that utilise “knowledge-deficit” models of belief, however, this study drew upon the vaccine anxieties framework (Leach and Fairhead, 2007), which views vaccines as being imbued with personal, historical, and political meaning. Findings suggest that important bodily, social, and political factors, including fear of side effects, the spread of misinformation prompted by poor messaging strategies, and distrust of government and international actors, influenced people’s COVID-19 vaccine attitudes and behaviours. It is hoped that the study’s findings will inform future policies and interventions related to vaccine uptake in Africa and globally.
Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
Musculoskeletal disorders and age-related musculoskeletal decline are major contributors to the burden of ill health seen in older subjects. Despite this increased burden, these chronic disorders of old age receive a relatively small proportion of national research funds. Much has been learned about fundamental processes involved in ageing from basic science research and this is leading to identification of key pathways that mediate ageing which may help the search for interventions to reduce age-related musculoskeletal decline. This short review will focus on the role of reactive oxygen species in age-related skeletal muscle decline and on the implications of this work for potential nutritional interventions in sarcopenia. The key physiological role of reactive oxygen species is now known to be in mediating redox signalling in muscle and other tissues and ageing leads to disruption of such pathways. In muscle, this is reflected in an age-related attenuation of specific adaptations and responses to contractile activity that impacts the ability of skeletal muscle from ageing individuals to respond to exercise. These pathways provides potential targets for identification of logical interventions that may help maintain muscle mass and function during ageing.
There is an increasing emphasis worldwide on breeding wheat cultivars with higher biomass and grain yield, whilst reducing excessive input of N fertilizers. Modern plant breeding has narrowed the genetic base of bread wheat, so exploring new sources of genetic variation for leaf photosynthesis traits and biomass to underpin grain yield improvement has become necessary. Our objectives were to quantify the genetic variability in a range of landrace-derived lines and elite bread wheat genotypes in flag-leaf photosynthesis traits, biomass and N-use efficiency for potential application in pre-breeding. Sixteen bread wheat genotypes including elite spring wheat cultivar Paragon × landrace crosses were tested in two field experiments in the UK. Averaging across years, pre-anthesis flag-leaf photosynthesis rate ranged amongst genotypes from 26.0 to 31.5 μmol/m2/s (P < 0.001) and post-anthesis from 14.2 to 18.6 μmol/m2/s (P < 0.001). Two landrace-derived lines had greater post-anthesis flag-leaf photosynthesis rate (P < 0.001) than their elite parent Paragon. There was a trend for a positive correlation among genotypes between post-anthesis flag-leaf photosynthesis rate and biomass (r = 0.47, P = 0.06). Two landrace derivatives showed higher post-anthesis flag-leaf stomatal conductance than Paragon. Our results indicated that introgression of traits from wider germplasm into elite UK modern wheat germplasm offers scope to raise flag-leaf photosynthetic rate and biomass.
Hemoglycin, a space polymer of glycine and iron, has been identified in the carbonaceous chondritic meteorites Allende, Acfer 086, Kaba, Sutter's Mill and Orgueil. Its core form has a mass of 1494 Da and is basically an antiparallel pair of polyglycine strands linked at each end by an iron atom. The polymer forms two- and three- dimensional lattices with an inter-vertex distance of 4.9 nm. Here the extraction technique for meteorites is applied to a 2.1 Gya fossil stromatolite to reveal the presence of hemoglycin by mass spectrometry. Intact ooids from a recent (3000 Ya) stromatolite exhibited the same visible hemoglycin fluorescence in response to x-rays as an intact crystal from the Orgueil meteorite. X-ray analysis confirmed the existence in ooids of an internal three-dimensional lattice of 4.9 nm inter-vertex spacing, matching the spacing of lattices in meteoritic crystals. FTIR measurements of acid-treated ooid and a Sutter's Mill meteoritic crystal both show the presence, via the splitting of the Amide I band, of an extended anti-parallel beta sheet structure. It seems probable that the copious in-fall of carbonaceous meteoritic material, from Archaean times onward, has left traces of hemoglycin in sedimentary carbonates and potentially has influenced ooid formation.
An altar to Mars dedicated by a soldier of legio XI Claudia is shown to have been removed from the fabric of Marton church during restoration work and, along with much of the other stone for the Romanesque tower, nave and chancel probably derived from the Roman small town of Segelocum, Littleborough on Trent. The name of the dedicator, G. IVLIVS ANTONINUS, is discussed in the context of legio XI Claudia deployment on the Lower Danube.
To characterize caregiver experiences in the context of advanced pediatric cancer by identifying individual (i.e., demographic factors, stress) and family context factors (i.e., family roles, social support) associated with caregiver strain.
Methods
Families of children (ages 5–25) with advanced cancer (i.e., physician-estimated prognosis < 60%, relapsed/refractory disease) were recruited from a large children’s hospital. Mothers (n = 55; 87% White) and fathers (n = 30; 83% White) reported on their caregiver strain, cancer-specific stress, general stress, social support, division of 7 family roles (e.g., medical care of ill child, household chores), and their satisfaction with each role.
Results
Parents reported moderate caregiver strain, cancer-specific stress, and general stress, and high social support and satisfaction with family roles. Fathers reported family roles were shared equally, whereas mothers reported either sharing roles or completing them independently. When accounting for income and partnership status, greater caregiver strain for mothers was associated with greater general stress, greater satisfaction with family roles, and lower social support. For fathers, greater caregiver strain was associated only with greater cancer-specific stress.
Significance of results
In the context of advanced pediatric cancer, fathers may experience caregiver strain as cancer-specific stress increases, whereas mothers’ strain may depend on broader family and social factors. Psychosocial providers should address general and cancer-specific stress within families, and provide resources for enhancing mothers’ social support. Additional research is needed with larger, more diverse samples to inform future intervention approaches.
Montmorillonite was found to be the dominant clay mineral in surface horizons of certain soils of the North Carolina Coastal Plain whereas a 2:1–2:2 intergrade clay mineral was dominant in subjacent horizons. In all soils where this clay mineral sequence was found, the surface horizon was low in pH (below 4·5) and high in organic matter content. In contrast, data from studies of other soils of this region (Weed and Nelson, 1962) show that: (1) montmorillonite occurs infrequently; (2) maximum accumulation of the 2:1–2:2 intergrade normally occurs in the surface horizon and decreases with depth in the profile; (3) organic matter contents are low; and (4) pH values are only moderately acid (pH 5–6).
It is theorized that the montmorillonite in the surface horizon of the soils studied originated by pedogenic weathering of the 2:1–2:2 intergrade clay mineral. The combined effects of low pH (below 4·5) and high organic matter content in surface horizons are believed to be the agents responsible for this mineral transformation. The protonation and solubilization (reverse of hydrolysis) of Al-polymers in the interlayer of expansible clay minerals will occur at or below pH 4·5 depending on the charge and steric effects of the interlayer. A low pH alone may cause this solubilization and thus mineral transformation, but in the soils studied the organic matter is believed to facilitate and accelerage the transformation. The intermediates of organic matter decomposition provide an acid environment, a source of protons, and a source of watersoluble mobile organic substances (principally fulvic acids) which have the ability to complex the solubilized aluminum and move it down the profile. This continuous removal of solubilized aluminum would provide for a favorable gradient for aluminum solubilization.
The drainage class or position in a catena is believed to be less important than the chemical factors in formation of montmorillonite from 2:1–2:2 intergrade, because montmorillonite is present in all drainage classes if the surface horizon is low in pH and high in organic matter.
When COVID-19 reached Sierra Leone, the government responded by implementing strict containment measures. While the effectiveness of such actions has been debated, the socioeconomic and political implications were undeniable. This qualitative study reveals that people suffered tremendously from economic insecurity, strains on social relationships, and civil rights violations, prompting many to perceive the COVID-19 pandemic as worse than the 2014–15 Ebola epidemic. These hardships have driven distrust of the government, which threatens continuing mitigation efforts. Using a feminist global health security frame, which recenters the protection of vulnerable individuals in relation to the state, we call for more contextually-relevant, civil society-informed pandemic responses.
The COVID-19 pandemic posed new challenges to physical and psychological well-being. Families with pediatric cancer patients were particularly vulnerable due to changes like children staying at home, hospital policy shifts, and caring for an immunocompromised child. Limited research exists on COVID-19's effects on these families. This study aimed to assess the pandemic's impact and identify psychosocial support gaps.
Methods
Participants (N = 256) were parents of children with cancer recruited via Facebook in partnership with Momcology®, a community-based organization for pediatric cancer, between February and May 2021. Qualitative analyses used open-ended responses about the pandemic’s impact on the family.
Results
Analysis revealed 6 themes, with positive and negative sentiments: family changes (n = 169; 61% negative), social isolation (n = 154; 100% negative), emotional impact (n = 143; 89% negative), school changes (n = 126; 80% negative), health-care changes (n = 111; 96% negative), and physical health (n = 49; 73% negative). Family changes overarched all themes and included financial strains, at-home schooling, and family bonding. Parents highlighted social isolation and the emotional impact of pandemic-related changes. School changes forced parents to balance remote-work and childcare. Health-care changes limited resources and visitation. Parents reported their children were less active and slept less but had fewer illnesses.
Significance of results
Many common pandemic challenges were exacerbated by the stress of caring for a child with cancer. Parents struggled most with loss of social support and feelings of isolation. Careful consideration should be given to providing resources for parents of children with cancer and their families.
Health technology assessment (HTA) organizations vary in terms of how they conduct assessments. We assess whether and to what extent HTA bodies have adopted societal and novel elements of value in their economic evaluations.
Methods
After categorizing “societal” and “novel” elements of value, we reviewed fifty-three HTA guidelines. We collected data on whether each guideline mentioned each societal or novel element of value, and if so, whether the guideline recommended the element’s inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.
Results
The HTA guidelines mention on average 5.9 of the twenty-one societal and novel value elements we identified (range 0–16), including 2.3 of the ten societal elements and 3.3 of the eleven novel value elements. Only four value elements (productivity, family spillover, equity, and transportation) appear in over half of the HTA guidelines, whereas thirteen value elements are mentioned in fewer than one-sixth of the guidelines, and two elements receive no mention. Most guidelines do not recommend value element inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.
Conclusions
Ideally, more HTA organizations will adopt guidelines for measuring societal and novel value elements, including analytic considerations. Importantly, simply recommending in guidelines that HTA bodies consider novel elements may not lead to their incorporation into assessments or ultimate decision making.
With the exponential growth in investment attention to brain health—solutions spanning brain wellness to mental health to neurological disorders—tech giants, payers, and biotechnology companies have been making forays into this field to identify technology solutions and pharmaceutical amplifiers. So far, their investments have had mixed results. The concept of open innovation (OI) was first coined by Henry Chesbrough to describe the paradigm by which enterprises allow free flow of ideas, products, and services from the outside to the inside and vice versa in order to remain competitive, particularly in rapidly evolving fields where there is abundant, relevant knowledge outside the traditional walls of the enterprise. In this article, we advocate for further exploration and advancement of OI in brain health.
Mental health problems often begin in early childhood. However, the associations of various individual and contextual risk factors with mental health in the preschool period are incompletely understood, particularly in low- to middle-income countries (LMICs) where multiple risk factors co-exist. To address this gap, we prospectively followed 981 children in a South African birth cohort, the Drakenstein Child Health Study, assessing pre-and postnatal exposures and risk factors. The predictive value of these factors for child mental health (assessed by the Child Behavior Checklist) was modeled using structural equation modeling. We identified two key pathways to greater externalizing behavior: (1) prenatal exposure to substances (alcohol and smoking) directly predicted increased externalizing behavior (β = 0.24, p < 0.001); this relationship was partially mediated by an aspect of infant temperament (negative emotionality; β = 0.05, p = 0.016); (2) lower socioeconomic status and associated maternal prenatal depression predicted more coercive parenting, which in turn predicted increased externalizing behavior (β = 0.18, p = 0.001). Findings in this high-risk LMIC cohort cohere with research from higher income contexts, and indicate the need to introduce integrated screening and intervention strategies for maternal prenatal substance use and depression, and promoting positive parenting across the preschool period.
Social policy agendas have generally failed to take account of the actual or potential role played by social alarms and telecare. This book draws on research and practice throughout the developed world. It documents the emergence of these important technologies and considers their potential in healthcare, social welfare and housing.
Background: Pituitary adenomas are common and often require complex multidisciplinary care with multiple specialists. This may result in a health care system that is challenging for patients to navigate. Audits of care at our institution revealed opportunities for improvement to better align care with patients’ needs. Methods: A quality improvement initiative that incorporated a patient advisory committee of patients who had received treatment for pituitary adenoma at our center and their family members was used to help identify opportunities for improvement. The patient-identified gaps in care included the need to coordinate and minimize appointments and the desire for better communication and education. Based on this information, changes were implemented to the pituitary program, including increasing access to the multidisciplinary clinic and developing a standardized and centralized triage process. Results: A pre and post-intervention analysis consisting of retrospective chart reviews revealed that these changes had an impact on wait times for first assessment, and a significant shift in location of this first visit – with a larger proportion of patients being seen in the multidisciplinary clinic after intervention. Conclusions: We demonstrate that patient involvement, beyond individual patient-physician interactions, can lead to meaningful and observable changes, and can improve the quality of care for pituitary adenoma.
The integration of biostratigraphical, wireline log, geophysical and available geochronological ages has identified two principal periods of volcanism in the Faroe–Shetland and Rockall basins. The first is pre-breakup, upper Danian to lower Thanetian: in the Rockall and Faroe–Shetland basins, isolated volcanic activity from 62 Ma to 58.7 Ma is identified in areas closely linked to the SSW–NNE structural fabric of the continental margin. Volcanic activity was concentrated at basin flank fissures and localised point sources. This rift-flank volcanism led to widespread volcanic ash deposition, localised lava flow fields and the formation of igneous centres. Some of the Hebridean and onshore central complexes (e.g., Rum) were uplifted and rapidly eroded during the later pre-breakup period, while additional accommodation space was developed in the adjacent offshore basins. Onset and termination of pre-breakup volcanism is correlated to intra-plate stress regimes in Europe, following the cessation of convergence of Africa and Europe in the Danian. The second is syn-breakup, upper Thanetian to Ypresian, initiated at ca.57 Ma in the Rockall and Faroe–Shetland basins. Initial high-volume extrusive igneous successions were focussed to the W in the Faroe–Shetland Basin. In the centre and E of the Faroe–Shetland and Rockall basins, separate eruption loci developed along pre-existing lineaments either as fissure or point-sourced lava fields. Short-term cessation of eruption at ~55.8 Ma was followed by resumption of flood basalt eruptions and a shift in focus to the NW. Fluctuations in the syn-breakup eruption tempo are reflected in the formation and subsequent rejuvenation of prominent unconformities, only previously recognised as a single erosive event. The W and northward shift of eruption focus, and the eruption of mid ocean ridge basalt-type lavas in the syn-breakup period reflect the onset of lithospheric thinning in the nascent North Atlantic Rift prior to flooding of the rift and eruption of the widespread lower Ypresian Balder Formation tephras.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
New guidelines for peanut allergy prevention in high-risk infants recommend introducing peanut during infancy but do not address breastfeeding or maternal peanut consumption. We assessed the independent and combined association of these factors with peanut sensitization in the general population CHILD birth cohort (N = 2759 mother–child dyads). Mothers reported peanut consumption during pregnancy, timing of first infant peanut consumption, and length of breastfeeding duration. Child peanut sensitization was determined by skin prick testing at 1, 3, and 5 years. Overall, 69% of mothers regularly consumed peanuts and 36% of infants were fed peanut in the first year (20% while breastfeeding and 16% after breastfeeding cessation). Infants who were introduced to peanut early (before 1 year) after breastfeeding cessation had a 66% reduced risk of sensitization at 5 years compared to those who were not (1.9% vs. 5.8% sensitization; aOR 0.34, 95% CI 0.14–0.68). This risk was further reduced if mothers introduced peanut early while breastfeeding and regularly consumed peanut themselves (0.3% sensitization; aOR 0.07, 0.01–0.25). In longitudinal analyses, these associations were driven by a higher odds of outgrowing early sensitization and a lower odds of late-onset sensitization. There was no apparent benefit (or harm) from maternal peanut consumption without breastfeeding. Taken together, these results suggest the combination of maternal peanut consumption and breastfeeding at the time of peanut introduction during infancy may help to decrease the risk of peanut sensitization. Mechanistic and clinical intervention studies are needed to confirm and understand this “triple exposure” hypothesis.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.