Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3.

BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Mindfulness-Based Interventions for the Reduction of Postoperative Pain in Hip and Knee Arthroplasty Patients: A Systematic Review and Meta-Analysis.

PURPOSE: The aim of this systematic review and meta-analysis is to evaluate the effect of mindfulness-based interventions (MBIs) on post-surgical pain in patients undergoing a total hip replacement (THR) or total knee replacement (TKR). METHODS: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A search of multiple databases, including PubMed and EMBASE, was performed for studies from database inception through March 2nd, 2022. Data were extracted, and pooled estimates of standardized mean differences in pain scores were calculated using a random effects model and inverse probability weighting. RESULTS: Two randomized control trials were eligible for inclusion (299 patients). The average ages of participants in each study were similar at 65.5 and 64.8 years, and both studies were predominantly female at 72.4% and 61.9%. The mindfulness intervention ranged from an eight-week program to a 20-minute session. Both individual studies reported statistically significant reductions in postoperative pain for MBI groups. The pooled standardized mean difference in pain scores for the MBI groups compared to the control groups was -1.94 (-3.39; -0.48). CONCLUSIONS: There exists preliminary evidence for the beneficial effect of MBIs on reducing the postoperative pain experience in this patient population. Given the significant consequences of postoperative pain and the necessity for non-opioid forms of analgesia, this topic represents a promising area of research that warrants future randomized control trials to better understand the role of MBIs for postoperative analgesia.

Further Examination of the Psychometric Properties of the Current Experiences Scale and Model of Resiliency.

Background: Stress-related disease is increasing, with high resilience proposed as protective. Whilst the Current Experiences Scale (CES) shows promise as a measure of resilience, its psychological correlates and relationship to psychological stress remain unclear. Objectives: (1) Further explore the psychometric properties of the CES, (2) identify modifiable psychological factors associated with the CES and (3) test a previously published model for the influence of adaptive strategies and stress management factors on resiliency and stress. Methods: N = 455 individuals (mean age = 47.8, 65.1% female) completed measures of adaptive strategies: mindfulness (Cognitive and Affective Mindfulness Scale-Revised), positive affect (Positive and Negative Affect Schedule) and gratitude (The Gratitude Questionnaire), stress management skills: coping (Measure of Current Status-A), depression (Patient Health Questionnaire-8) and anxiety (General Anxiety Disorder Assessment) and outcomes: resilience (CES) and stress (Perceived Stress Scale). Cronbach's alpha and confirmatory factor analysis (CFA) examined the psychometric properties of the CES. Multivariable regression identified psychological variables associated with resilience. Structural equation modelling (SEM) tested the previously published model for resilience. Results: The CES and its subscales showed good internal consistency (ɑ = .75-.93). The 23-item CES produced excellent results for model fit (Root Mean Square Error of Approximation (RMSEA) = .07, Standardized Root Mean Square Residual (SRMR) = .06, Comparative Fit Index (CFI) = .99; Tucker-Lewis Index (TLI) = .99). Higher gratitude (P < .0001), mindfulness (P < .0001), positive affect (P < .0001) and coping (P < .0001) were associated with higher resilience. Depression (P = .23) and anxiety (P = .34) were not. A model of resilience which included gratitude, mindfulness, positive affect and coping as determinants of resilience and perceived stress performed well (RMSEA = .03, SRMR = .02, CFI = .99; TLI = .99). Conclusions: The CES was validated in a large sample. The association of gratitude, mindfulness, positive affect and coping with resilience may guide practitioners seeking to design resilience-enhancing programs.

A meteorological dataset of the West African monsoon during the 2016 DACCIWA campaign.

As part of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) project, extensive in-situ measurements of the southern West African atmospheric boundary layer (ABL) have been performed at three supersites Kumasi (Ghana), Savè (Benin) and Ile-Ife (Nigeria) during the 2016 monsoon period (June and July). The measurements were designed to provide data for advancing our understanding of the relevant processes governing the formation, persistence and dissolution of nocturnal low-level stratus clouds and their influence on the daytime ABL in southern West Africa. An extensive low-level cloud deck often forms during the night and persists long into the following day strongly influencing the ABL diurnal cycle. Although the clouds are of a high significance for the regional climate, the dearth of observations in this region has hindered process understanding. Here, an overview of the measurements ranging from near-surface observations, cloud characteristics, aerosol and precipitation to the dynamics and thermodynamics in the ABL and above, and data processing is given. So-far achieved scientific findings, based on the dataset analyses, are briefly overviewed.

Ankle Dorsiflexion Affects Hip and Knee Biomechanics During Landing.

BACKGROUND: Restricted ankle dorsiflexion range of motion (DFROM) has been linked to lower extremity biomechanics that place an athlete at higher risk for injury. Whether reduced DFROM during dynamic movements is due to restrictions in joint motion or underutilization of available ankle DFROM motion is unclear. HYPOTHESIS: We hypothesized that both lesser total ankle DFROM and underutilization of available motion would lead to high-risk biomechanics (ie, greater knee abduction, reduced knee flexion). STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Nineteen active female athletes (age, 20.0 ± 1.3 years; height, 1.61 ± 0.06 m; mass, 67.0 ± 10.7 kg) participated. Maximal ankle DFROM (clinical measure of ankle DFROM [DF-CLIN]) was measured in a weightbearing position with the knee flexed. Lower extremity biomechanics were measured during a drop vertical jump with 3-dimensional motion and force plate analysis. The percent of available DFROM used during landing (DF-%USED) was calculated as the peak DFROM observed during landing divided by DF-CLIN. Univariate linear regressions were performed to identify whether DF-CLIN or DF-%USED predicted knee and hip biomechanics commonly associated with injury risk. RESULTS: For every 1.0° less of DF-CLIN, there was a 1.0° decrease in hip flexion excursion (r2 = 0.21, P = 0.05), 1.2° decrease in peak knee flexion angles (r2 = 0.37, P = 0.01), 0.9° decrease in knee flexion excursion (r2 = 0.40, P = 0.004), 0.002 N·m·N-1·cm-1 decrease in hip extensor work (r2 = 0.28, P = 0.02), and 0.001 N·m·N-1·cm-1 decrease in knee extensor work (r2 = 0.21, P = 0.05). For every 10% less of DF-%USED, there was a 3.2° increase in peak knee abduction angles (r2 = 0.26, P = 0.03) and 0.01 N·m·N-1·cm-1 lesser knee extensor work (r2 = 0.25, P = 0.03). CONCLUSION: Lower levels of both ankle DFROM and DF-%USED are associated with biomechanics that are considered to be associated with a higher risk of sustaining injury. CLINICAL RELEVANCE: While total ankle DFROM can predict some aberrant movement patterns, underutilization of available ankle DFROM can also lead to higher risk movement strategies. In addition to joint specific mobility training, clinicians should incorporate biomechanical interventions and technique feedback to promote the utilization of available motion.

Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model.

The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.

Probing carrier lifetimes in photovoltaic materials using subsurface two-photon microscopy.

Accurately measuring the bulk minority carrier lifetime is one of the greatest challenges in evaluating photoactive materials used in photovoltaic cells. One-photon time-resolved photoluminescence decay measurements are commonly used to measure lifetimes of direct bandgap materials. However, because the incident photons have energies higher than the bandgap of the semiconductor, most carriers are generated close to the surface, where surface defects cause inaccurate lifetime measurements. Here we show that two-photon absorption permits sub-surface optical excitation, which allows us to decouple surface and bulk recombination processes even in unpassivated samples. Thus with two-photon microscopy we probe the bulk minority carrier lifetime of photovoltaic semiconductors. We demonstrate how the traditional one-photon technique can underestimate the bulk lifetime in a CdTe crystal by 10× and show that two-photon excitation more accurately measures the bulk lifetime. Finally, we generate multi-dimensional spatial maps of optoelectronic properties in the bulk of these materials using two-photon excitation.

The psychodynamics of transference--a virtual reality model.

OBJECTIVE: Virtual reality is not only being utilized increasingly as an enhancement for diagnosis and treatment of psychiatric illness, but it also can be used to model theories, generate hypotheses, and provide a new context for teaching psychodynamic therapy. Here we describe the use of an online virtual world--Second Life--as a heuristic tool for understanding and teaching a key psychoanalytic concept, transference. METHODS: Using an extended vignette to illustrate the results of the modeling process, we explore teaching the vicissitudes of object relationships by means of analogs in virtual reality. RESULTS: Simple reframing operations demonstrate how traditional dynamic theories of psychiatric treatment can be brought to life in simulations using modern computer technology. CONCLUSIONS: Virtual worlds offer a helpful analogy in teaching complex psychoanalytic concepts, such as transference.

Interfacial alloy hydride destabilization in Mg/Pd thin films.

Recently, a large increase in the equilibrium hydrogen pressure has been reported for MG thin films capped with a Pd layer. We show that this increase is due to intermixing of Mg and Pd, as opposed to a strain effect as previously claimed. Transmission electron microscopy and depth profiling x-ray photoemission spectroscopy are used to directly measure interfacial intermixing between Mg and Pd, and we find that intermixing and equilibrium hydrogen pressure both increase with annealing. We present a thermodynamic model of the effect of alloying on equilibrium pressure, and find that the observed equilibrium pressure increase is consistent with the observed thickness of the intermixed region, which is of the order of a few nm. We also show that stress measured during hydrogenation corresponds to a negligible increase in equilibrium pressure.

Genetics in non-genetic model systems.

The past few decades have seen the field of genetic engineering evolve at a rapid pace, with neuroscientists now equipped with a wide range of tools for the manipulation of an animal's genome in order to study brain function. However, the number of species to which these technologies have been applied, namely the fruit fly, C. elegans, zebrafish and mouse, remains relatively few. This review will discuss the variety of approaches to genetic modification that have been developed in such traditional 'genetic systems', and highlight the progress that has been made to translate these technologies to alternative species such as rats, monkeys and birds, where certain neurobiological questions may be better studied.

Medical professionalism: a tale of two doctors.

The AMA's social media guidelines provide physicians with some basic rules for maintaining professional boundaries when engaging in online activities. Left unanswered are questions about how these guidelines are to be implemented by physicians of different generations. By examining the issues of privacy and technological skill through the eyes of digital natives and digital immigrants, the challenges associated with medical e-professionalism become clear.

Crime and hate in virtual worlds: a new playground for the ID?

Virtual worlds offer the potential for friendship, compassionate listening and support, and even love for 15 million users worldwide. But virtual analogs of crimes such as rape, murder, and pedophilia also exist within these worlds. The writings of Freud and Winnicott provide one model for understanding what may motivate these virtual crimes and how to think about them clinically. Psychiatric treatment can potentially benefit if therapists discuss virtual world use with patients as a way of understanding their inner lives.

Comparing the role of the anterior cingulate cortex and 6-hydroxydopamine nucleus accumbens lesions on operant effort-based decision making.

Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost-benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post-operatively, excitotoxic ACC lesions caused a significant bias away from HR choices compared with sham-lesioned animals. There was no slowing in the speed of lever pressing and no correlation between time to complete the FR requirement and choice performance. Unexpectedly, no such alteration in choice allocation was observed in animals following 6-hydroxydopamine NAc lesions. However, these rats were consistently slower to initiate responding when cued to commence each trial and also showed a reduction in food hoarding on a species-typical foraging task. Taken together, this implies that only ACC lesions, and not 6-hydroxydopamine NAc lesions as performed here, cause a bias away from investing effort for greater reward when choosing between competing options

The role of GABAbeta2 subunit-containing receptors in mediating the anticonvulsant and sedative effects of loreclezole.

The majority of inhibitory neurotransmission in the brain is mediated by the gamma-aminobutyric acid (GABA) type A (GABA(A)) receptor. The anticonvulsant loreclezole largely acts by potentiating GABA(A) receptors containing beta2 and beta3 subunits. We used a genetically modified mouse containing a loreclezole-insensitive beta2 subunit (beta2N265S) to determine the role of this subunit in mediating the sedative and anticonvulsive effects of loreclezole. Sedation was assessed by measuring spontaneous locomotor activity and beam walking performance, and anticonvulsant efficacy was determined by pentylenetetrazole (PTZ) and amygdala kindling-induced seizures. The beta2N265S mice did not exhibit loreclezole-mediated sedation as shown by normal locomotor activity and beam walking performance. However, loreclezole also failed to provide significant protection against PTZ-induced seizures in the beta2N265S mice. Reduced efficacy against amygdala-kindled seizures, both acutely and over a 13-day chronic dosing study, was also observed in beta2N265S mice. These results suggest that the majority of the sedative effects and a significant proportion of the anticonvulsant efficacy of loreclezole are mediated via beta2-containing GABA(A) receptors.

High cell density induces spontaneous bifurcations of dissolved oxygen controllers during CHO cell fermentations.

High cell density cultures of CHO cells growing in a bioreactor under dissolved oxygen control were found to undergo spontaneous bifurcations and a subsequent loss of stability some time into the fermentation. This loss of stability was manifested by sustained and amplified oscillations in the bioreactor dissolved oxygen concentration and in the oxygen gas flow rate to the reactor. To identify potential biological and operational causes for the phenomenon, linear stability analysis was applied in a neighborhood of the experimentally observed bifurcation point. The analysis revealed that two steady state process gains, K(P1) and K(P2), regulated k(l)a and gas phase oxygen concentration inputs, respectively, and the magnitude of K(P1) was found to determine system stability about the bifurcation point. The magnitude of K(P1), and hence the corresponding open-loop steady state gain K(OL1), scaled linearly with the bioreactor cell density, increasing with increasing cell density. These results allowed the generation of a fermentation stability diagram, which partitioned K(C)-N operating space into stable and unstable regions separated by the loci of predicted critically stable controller constants, K(C,critical), as a function of bioreactor cell density. This consistency of this operating diagram with experimentally observed changes in system stability was demonstrated. We conclude that time-dependent increases in cell density are the cause of the observed instabilities and that cell density is the critical bifurcation parameter. The results of this study should be readily applicable to the design of a more robust controller.

The Role of Psychiatry in the Management of Acute Trauma Surgery Patients.

BACKGROUND: Trauma is a leading cause of death and disability in the United States, with high prevalence and recidivism in individuals with psychiatric and substance abuse disorders. Half of these disorders go undiagnosed by the trauma team, resulting in adverse public health and economic consequences. METHOD: In a 16-week pilot study in the emergency department of an inner-city tertiary care hospital, a psychiatrist was integrated into the trauma surgery team by responding to all traumas and rounding with the staff 1 shift per week (March 1, 2000, through June 31, 2000). During this 16-week period, 375 patients passed through the trauma surgery service. Data on the frequency of psychiatric consultations were compared with those for a retrospectively selected control group consisting of all 360 patients passing through the trauma surgery service during the corresponding 16 weeks of the previous year (March 1, 1999, through June 31, 1999). To determine the prevalence of psychopathology, eligible patients seen during the psychiatrist's shift (N = 28) were assessed with a semistructured interview, and charts for eligible patients seen in the corresponding shift during the previous year (N = 18) were assessed according to the same criteria. Before the study, a 10-item, self-report questionnaire was completed by 16 (73%) of the 22 emergency medicine physicians who serve as front-line staff members. The survey assessed physicians' attitudes toward psychiatric consultation for psychopathology and addictions in trauma patients. RESULTS: Based on DSM-IV screening criteria, the prevalence of preexisting psychopathology was 68% (19/28), but before the psychiatrist's involvement, only 12% (2/16) of physicians surveyed had considered consulting psychiatry, even for patients with gross psychopathology. Before the psychiatrist's integration into the 16-week study period, 75% (9/12) of trauma patients were discharged without psychiatric consultation despite the fact that more than half had documented substance abuse. After the psychiatrist joined the team, staff awareness of psychopathology sharpened. The number of patients treated for a psychiatric disorder that was often the proximal cause of the traumatic event nearly doubled, even on shifts not covered in the study. CONCLUSIONS: The ability to identify and treat coexisting psychopathology requires trauma surgeons to routinely incorporate a psychiatrist into their evaluation and treatment algorithm. Such a change in physician awareness and motivation hinges on a psychiatrist's visible presence (even if brief) and regular, active participation in the emergency department.

Celebrity Patients, VIPs, and Potentates.

BACKGROUND: During the second half of the 20th century, the literature on the doctor-patient relationship mainly dealt with the management of "difficult" (personality-disordered) patients. Similar problems, however, surround other types of "special" patients. METHOD: An overview and analysis of the literature were conducted. As a result, such patients can be subcategorized by their main presentations; each requires a specific management strategy. RESULTS: Three types of "special" patients stir up irrational feelings in their caregivers. Sick celebrities threaten to focus public scrutiny on the private world of medical caregivers. VIPs generate awe in caregivers, with loss of the objectivity essential to the practice of scientific medicine. Potentates unearth narcissism in the caregiver-patient relationship, which triggers a struggle between power and shame. Pride, privacy, and the staff's need to be in control are all threatened by introduction of the special patient into medicine's closed culture. CONCLUSION: The privacy that is owed to sick celebrities should be extended to protect overexposed staff. The awe and loss of medical objectivity that VIPs generate are counteracted by team leadership dedicated to avoiding any deviation from standard clinical procedure. Moreover, the collective ill will surrounding potentates can be neutralized by reassuring them that they are "special"-and by caregivers mending their own vulnerable self-esteem.