Compound-Nucleus and Doorway-State Decays of ß-Delayed Neutron Emitters

We investigated decays of ^{51,52,53}K at the ISOLDE Decay Station at CERN in order to understand the mechanism of the ß-delayed neutron-emission (ßn) process. The experiment quantified neutron and γ-ray emission paths for each precursor. We used this information to test the hypothesis, first formulated by Bohr in 1939, that neutrons in the ßn process originate from the structureless "compound nucleus." The data are consistent with this postulate for most of the observed decay paths. The agreement, however, is surprising because the compound-nucleus stage should not be achieved in the studied ß decay due to insufficient excitation energy and level densities in the neutron emitter. In the ^{53}K ßn decay, we found a preferential population of the first excited state in ^{52}Ca that contradicted Bohr's hypothesis. The latter was interpreted as evidence for direct neutron emission sensitive to the structure of the neutron-unbound state. We propose that the observed nonstatistical neutron emission proceeds through the coupling with nearby doorway states that have large neutron-emission probabilities. The appearance of "compound-nucleus" decay is caused by the aggregated small contributions of multiple doorway states at higher excitation energy.

An exploration into self-reported inactivity behaviours of adults with an intellectual disability using physical activity questionnaires.

BACKGROUND: Inactivity is a correlate of adverse health. Adults with an intellectual disability (ID) are more inactive than the general population and often present with more complex health issues. Self-reported activity questionnaires such as the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and Rapid Assessment of Physical Activity (RAPA) questionnaire are the predominant source of activity information because of their low cost, non-invasive nature, ease of administration and interpretation of results. METHODS: Correlates of inactivity among the general and ID populations were identified through a literature scoping review. Inactivity was measured using the RAPA and the IPAQ-SF. A multiple-imputation chained equation was used to impute missing data. Using Pearson chi-squared analyses, relationships between these correlates as well as covariates of age, sex, level of ID, body mass index (BMI) and aetiology, and RAPA and IPAQ-SF categories were explored. Logistic regression provided more detailed analyses. Results were summarised using the Systems of Sedentary Behaviour framework. Spearman correlations examined the IPAQ-SF and RAPA relationships. RESULTS: Three correlates for inactivity emerged from the IPAQ-SF and RAPA questionnaire. Up after 07:00 h was a correlate for both. Difficulty walking 100 yards and epilepsy were additional correlates of inactivity. Weak but significant correlations were seen between IPAQ-SF and RAPA scores. CONCLUSIONS: High inactivity levels are present in adults with an ID. The IPAQ-SF and RAPA questionnaires are weakly correlated.

Training during the COVID-19 pandemic: the experience of public health registrars in the London and Kent, Surrey, Sussex training programme.

BACKGROUND: Public Health registrars (SpRs) were an important component of the workforce that contributed to the COVID-19 response. This study explores their contribution and the impact the early stages of the pandemic had on their learning and training. METHODS: Data were collected from SpRs in the London and Kent, Surrey, Sussex training programme between July and September 2020 through a mixture of questionnaires and semi-structured interviews. A thematic analysis of interview transcripts was undertaken to identify themes. RESULTS: 35/128 SpRs responded to the survey and 11 were interviewed. SpRs were placed across a range of organizations and made a significant contribution to the COVID-19 response. Overall, SpRs learned important skills but working on the response may for some have impacted negatively on training. A number of facilitators and barriers to learning were identified. CONCLUSION: The study findings highlight the opportunities for learning created by the pandemic. However, changing projects and the desire of SpRs to contribute to the response meant the impacts on training were mixed. Future deployment of SpRs should consider the balance of responsibility and pace when delegating work, as well as the need to supervise effectively and support remote working to maintain good mental wellbeing.

Buffered Lugol's Iodine Preserves DNA Fragment Lengths.

Museum collections play a pivotal role in the advancement of biological science by preserving phenotypic and genotypic history and variation. Recently, contrast-enhanced X-ray computed tomography (CT) has aided these advances by allowing improved visualization of internal soft tissues. However, vouchered specimens could be at risk if staining techniques are destructive. For instance, the pH of unbuffered Lugol's iodine (I2KI) may be low enough to damage deoxyribonucleic acid (DNA). The extent of this risk is unknown due to a lack of rigorous evaluation of DNA quality between control and experimental samples. Here, we used formalin-fixed mice to document DNA concentrations and fragment lengths in nonstained, ethanol-preserved controls and 3 iodine-based staining preparations: (1) 1.25% weight-by-volume (wt/vol.) alcoholic iodine (I2E); (2) 3.75% wt/vol. I2KI; and (3) 3.75% wt/vol. buffered I2KI. We tested a null hypothesis of no significant difference in DNA concentrations and fragment lengths between control and treatment samples. We found that DNA concentration decreases because of staining-potentially an effect of measuring intact double-stranded DNA only. Fragment lengths, however, were significantly higher for buffered I2KI and control samples, which were not, themselves, significantly different. Our results implicate buffered I2KI as the appropriate choice for contrast-enhanced CT imaging of museum wet collections to safely maximize their potential for understanding genetic and phenotypic diversity.

Las colecciones de museos juegan un papel crucial en el avance de la ciencia biológica al preservar la historia y la variación fenotípica y genotípica. Recientemente, la tomografía computarizada (CT) mejorada con contraste ha facilitado estos avances al permitir una mejor visualización de los tejidos blandos internos. Sin embargo, los especímenes con vales podrían estar en riesgo si las técnicas de tinción son destructivas. Por ejemplo, el pH del yodo de Lugol sin tamponar (I2KI) puede ser lo suficientemente bajo como para dañar el ADN. Se desconoce el alcance de este riesgo debido a la falta de una evaluación rigurosa de la calidad del ADN entre las muestras de control y las experimentales. Aquí utilizamos ratones fijados en formalina para documentar las concentraciones de ADN y las longitudes de los fragmentos en controles no teñidos, preservados en etanol, y en tres preparaciones de tinción basadas en yodo: (i) 1.25% peso/volumen (wt/vol.) de yodo alcohólico (I2E), (ii) 3.75% wt/vol. I2KI, y (iii) 3.75% wt/vol. I2KI tamponado. Probamos una hipótesis nula de que no hay diferencias significativas en las concentraciones de ADN y las longitudes de los fragmentos entre las muestras de control y las de tratamiento. Encontramos que la concentración de ADN disminuye debido a la tinción, potencialmente un efecto de medir solo ADN de doble cadena intacto. Sin embargo, las longitudes de los fragmentos fueron significativamente mayores para I2KI tamponado y las muestras de control, que no fueron, ellas mismas, significativamente diferentes. Nuestros resultados implican que I2KI tamponado es la opción adecuada para la imagenología CT mejorada con contraste de colecciones húmedas de museos para maximizar de manera segura su potencial para comprender la diversidad genética y fenotípica.

Immune and non-immune functions of adipose tissue leukocytes.

Adipose tissue is a complex dynamic organ with whole-body immunometabolic influence. Much of the work into understanding the role of immune cells in adipose tissue has been in the context of obesity. These investigations have also uncovered a range of typical (immune) and non-typical functions exerted by adipose tissue leukocytes. Here we provide an overview of the adipose tissue immune system, including its role as an immune reservoir in the whole-body response to infection and as a site of parasitic and viral infections. We also describe the functional roles of specialized immunological structures found within adipose tissue. However, our main focus is on the recently discovered 'non-immune' functions of adipose tissue immune cells, which include the regulation of adipocyte homeostasis, as well as responses to changing nutrient status and body temperature. In doing so, we outline the therapeutic potential of the adipose tissue immune system in health and disease.

Is decolonization to prevent Panton-Valentine leukocidin-positive Staphylococcus aureus infection in the population effective? A systematic review.

Panton-Valentine leukocidin (PVL) -producing Staphylococcus aureus is associated with recurrent skin and soft tissue infections and occasionally invasive infections. There is limited evidence to support current public health guidance on decolonization of cases and household contacts. This systematic review (CRD42020189906) investigated the efficacy of decolonization against PVL-positive S. aureus to inform future public health practice. It included studies of cases with PVL-positive infections providing information on the efficacy of decolonization of cases, carriers, or contacts of cases. Studies were assessed for the risk of bias using the GRADE approach and summarized to inform a narrative synthesis. The search identified 20, mostly observational, studies with small samples and lacking control groups. Studies with longer follow-ups found that, while early post-decolonization screening was negative for most individuals, testing over subsequent months identified re-colonization in some. There is no high-quality evidence to show whether decolonization is effective in reducing (re)infection or long-term carriage of PVL-positive S. aureus and the low-quality evidence available indicates it may not be effective in eradicating carriage or reducing future disease. Furthermore, there may be risks associated with decolonization, e.g., potentially increased risk of infection from other microbes, opportunity costs and negative impacts of repeated testing for asymptomatic carriage. Further research is required to better understand what affects the ability of decolonization efforts to reduce risk to cases and their contacts, including strain, host and environmental factors.

Responding to eruptive transitions during the 2020-2021 eruption of La Soufrière volcano, St. Vincent.

A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid synthesis and communication of multiple datasets with prognoses. The 2020-2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9-22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest. Here we show how the development of an evolving conceptual model, and the expression of uncertainties via both elicitation and scenarios associated with this model, were key to anticipating this transition. This not only required input from multiple monitoring datasets but contextualisation via state-of-the-art hazard assessments, and evidence-based knowledge of critical decision-making timescales and community needs. In addition, we share strategies employed as a consequence of constraints on recognising and responding to eruptive transitions in a resource-constrained setting, which may guide similarly challenged volcano observatories worldwide.

Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis.

AIMS/HYPOTHESIS: The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells. METHODS: We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. RESULTS: The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. CONCLUSIONS/INTERPRETATION: The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.

The use of an intermittent terbinafine regimen for the treatment of dermatophyte toenail onychomycosis.

OBJECTIVE: To compare the efficacy and safety of intermittent terbinafine with standard courses of terbinafine and itraconazole for dermatophyte toenail onychomycosis. DESIGN: Data from a Canadian study of continuous terbinafine (CTERB) and intermittent itraconazole (III) was compared to an intermittent terbinafine regimen (TOT) using similar protocol to the randomized study. INTERVENTIONS: Terbinafine 250 mg/day for 4 weeks followed by 4 weeks of no terbinafine and then an additional 4 weeks of terbinafine 250 mg/day (TOT); terbinafine 250 mg/day for 12 weeks (CTERB); itraconazole pulse of 200 mg twice daily for 7 days on, 21 days off, three pulses given (III). RESULTS: At 72 weeks, mycological cure rates (negative KOH and culture) were 36 of 43 (83.7%), 25 of 32 (78.1%), and 17 of 30 (56.7%), for the TOT, CTERB, and III groups, respectively (P = 0.01 for TOT vs. III). Effective cure rates (simultaneous mycological cure and < or =10% nail plate involvement) were 34 of 43 (79.1%), 21 of 32 (65.6%), and 11 of 30 (36.7%), respectively (P < 0.001 for TOT vs. III; P = 0.02 for CTERB vs. III). No significant differences in effective and mycological cure rates were noted between the two terbinafine groups. Adverse events reported were similar to those reported in the respective package inserts. Most adverse events were mild to moderate, transient, and did not require interruption of the drug regimens. No serious adverse events were reported. CONCLUSIONS: A TOT intermittent terbinafine regimen provided similar efficacy and safety to the gold standard continuous terbinafine regimen and better effective cure rates than pulse itraconazole therapy.

Activation of alpha(v)beta3-vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the cytoplasmic domain of beta3.

Integrin receptors serve as mechanical links between the cell and its structural environment. Using alpha(v)beta3 integrin expressed in K562 cells as a model system, the process by which the mechanical connection between alpha(v)beta3 and vitronectin develops was analyzed by measuring the resistance of these bonds to mechanical separation. Three distinct stages of activation, as defined by increases in the alpha(v)beta3-vitronectin binding strength, were defined by mutational, biochemical, and biomechanical analyses. Activation to the low binding strength stage 1 occurs through interaction with the vitronectin ligand and leads to the phosphorylation of Y747 in the beta3 subunit. Stage 2 is characterized by a 4-fold increase in binding strength and is dependent on stage1 and the phosphorylation of Y747. Stage 3 is characterized by a further 2.5-fold increase in binding strength and is dependent on stage 2 events and the availability of Y759 for interaction with cellular proteins. The Y747F mutant blocked the transition from stage 1 to stage 2, and the Y759F blocked the transition from stage 2 to stage 3. The data suggest a model for tension-induced activation of alpha(v)beta3 integrin.

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.

BACKGROUND: Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long? METHODS: 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models. FINDINGS: Cognition averaged 0.8 MMSE (mini-mental state examination) points better (95% CI 0.5-1.2; p<0.0001) and functionality 1.0 BADLS points better (0.5-1.6; p<0.0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0.4) or progression of disability (58% vs 59% at 3 years; p=0.4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0.97 (95% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 0.74-1.24; p=0.7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil. INTERPRETATION: Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than cholinesterase inhibitors are needed for Alzheimer's disease.

Ciclopirox nail lacquer 8% for the treatment of onychomycosis: a Canadian perspective.

Onychomycosis is prevalent in the Canadian population, and risk factors, such as old age and diabetes, are increasing. This condition has traditionally been treated using oral antifungal agents with varying degrees of success. Recently, ciclopirox nail lacquer 8% solution became the first topical agent approved in Canada for onychomycosis. Ciclopirox nail lacquer may be safe and effective for the treatment of onychomycosis, and certain candidates may benefit from therapy. Ciclopirox may be implicated for prophylactic use in order to prevent recurrent infection and may be used in combination with oral agents.

Administration of colony stimulating factor-1 to toothless osteopetrotic rats normalizes osteoblast, but not osteoclast, gene expression.

The toothless (tl) osteopetrotic mutation in the rat is characterized by generalized skeletal sclerosis, a severe reduction in the numbers of osteoclasts, monocytes, and macrophages, and absence of tooth eruption. Studies examining gene expression in bone-derived cells of tl rats and their normal littermates have shown that genes related to osteoblast function are aberrantly expressed in tl rats compared to normal littemates. We have previously shown that exogenous administration of colony stimulating factor-1 (CSF-1) to tl rats results in a dramatic reduction of the skeletal sclerosis and significant increases in the number of osteoclasts. Thus, we examined the effects of CSF-1 on osteoblast and osteoclast gene expression in tl rats as demonstrated by Northern blot analysis. While osteoblast-related gene expression as reflected by mRNA levels of alkaline phosphatase, osteocalcin, osteopontin, and type I collagen was normalized, osteoclast-related gene expression, as reflected by mRNA levels of carbonic anhydrase II and tartrate-resistant adenosine triphosphatase, remained significantly lower in CSF-1-treated tl rats compared to untreated normal littermates. Since previous studies have not demonstrated the CSF-1 receptor on osteoblasts, these results suggest that osteoblast abnormalities in tl rats are an effect of the osteopetrotic condition rather than the cause of the disease.

Patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure in two community hospitals.

Because they provide relief of symptoms and reduce mortality, angiotensin-converting enzyme (ACE) inhibitors have become a highly recommended part of the pharmacologic treatment of patients with congestive heart failure (CHF). Although clinical trials suggest that 80% to 90% of patients with CHF tolerate ACE inhibitors, recent surveys reveal that for fewer than this number of patients are actually receiving these drugs. The reasons for this discrepancy are not known. To better understand physician-prescribing behavior, the current study examined the demographic, clinical, laboratory, and medical care characteristics of patients treated and not treated with ACE inhibitors during hospitalization for decompensated CHF. The charts of a consecutive series of patients admitted to 2 acute care hospitals during 1992 (n = 424) were reviewed and comparisons made between those receiving and not receiving ACE inhibitors at the time of hospital admission and hospital discharge. In addition, measures of in-hospital and postdischarge outcome were compared between the groups. The results revealed significant differences in certain demographic variables (e.g., patient age), clinical measures (e.g., left ventricular ejection fraction and serum creatinine), management issues (e.g., documentation of left ventricular function and documentation of etiology of CHF), and treatment strategies (e.g., ancillary drug use). Few differences were noted in measures of severity of CHF (e.g., New York Heart Association functional class and serum sodium level). Death rates were significantly higher for those not receiving ACE inhibitors. Patterns that emerged that could explain under-prescription ACE inhibitors included older age, worse renal function, left ventricular diastolic dysfunction, use of alternate vasodilators, and overall less intense medical management. Programs to educate care providers regarding the proper use of ACE inhibitors in CHF are recommended.

Predictors and determinants of hospital length of stay in congestive heart failure in ten community hospitals.

BACKGROUND: Little is known about the actual determinants of hospital length of stay (LOS) among patients admitted with congestive heart failure (CHF), in spite of its economic impact. To increase understanding of these factors, we examined the demographic, clinical, laboratory, and treatment characteristics of patients hospitalized with decompensated CHF. METHODS: The charts of consecutive patients admitted to 10 acute care community hospitals during 1995 were reviewed. The relationship between LOS and more than 140 patient-specific variables were examined. First, patient characteristics identifiable within the first 24 hours of hospitalization were examined for their relationship with LOS. Then, variables indicative of the processes of care and response to treatment were studied. Finally, administrative data were added to yield the final model for LOS. RESULTS: During the study period 1402 patients were admitted to the participating centers. The patients were predominantly elderly with moderately severe or severe CHF. With stepwise multiple linear regression, 5% of the variation in LOS could be explained by baseline characteristics alone (r = 0.22, p < 0.0001). When treatment and response variables were added to this model, 15% of the variation in LOS could be explained (r = 0.39, p < 0.0001). When administrative data were added, the final model explained 31% of the variation in LOS (r = 0.56, p < 0.0001). CONCLUSIONS: We conclude that LOS among patients hospitalized with decompensated CHF is partially related to patient demographics, severity of illness, management modalities, response to treatment, and administrative data. However, significant residual variation in LOS exists, which cannot be explained by these factors. These observations may be of value in the design and implementation of initiatives aimed at reducing resource utilization and improving quality of care in CHF.

The use of the laryngeal mask airway to facilitate the insertion of a percutaneous tracheostomy.

We report the use of the laryngeal mask airway to facilitate the insertion of a percutaneous tracheostomy (Ciaglia kit) in two patients. This method has not been reported previously. We believe that in selected patients the technique described increases the ease of placement of a percutaneous tracheostomy.

Evaluations of children who have disclosed sexual abuse via facilitated communication.

OBJECTIVE: To review the findings of interdisciplinary team evaluations of children who disclosed sexual abuse via facilitated communication. DESIGN: Case series. SETTING: Tertiary care hospital outpatient child sexual abuse program in central New York. PATIENTS: Between January 1990 and March 1993, 13 children who disclosed sexual abuse via facilitated communication and were referred to a university hospital child abuse referral and evaluation center. The range of previously determined developmental diagnosis included mental retardation, speech delay, and autism. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Medical records were reviewed for (1) disclosure, (2) physical evidence, (3) child's behavioral and medical history, (4) disclosures by siblings, (5) perpetrator's confession, (6) child protective services determinations, and (7) court findings. RESULTS: Four children had evidence of sexual abuse: two had physical findings consistent with sexual abuse, one also disclosed the allegation verbally, and one perpetrator confessed. CONCLUSIONS: These results neither support nor refute validation of facilitated communication. However, many children had other evidence of sexual abuse, suggesting that each child's case should be evaluated without bias.

Selective reduction: an unfortunate misnomer.

When the number of fetuses in multifetal pregnancies is reduced in the first trimester, the gender and karyotypic status of individual fetuses are rarely, if ever known. In these cases, the only basis for choosing to terminate a particular fetus is the physical location of its sac. The term "selective reduction" is therefore inaccurate, and may be psychologically damaging because it implies that specific fetuses have been targeted. We believe that this procedure should be referred to as multifetal pregnancy reduction.

The role of sonography in assessing severity of fetal anemia in Rh- and Kell-isoimmunized pregnancies.

Fetal hematocrit values of blood obtained by percutaneous umbilical blood sampling were correlated with ultrasound findings in 35 samples from 15 pregnancies undergoing evaluation for Rh or Kell sensitization. Intravascular fetal transfusion was performed after a low hematocrit was obtained on 29 of 35 occasions. All fetuses with sonographic evidence of hydrops had a hematocrit of 15% or less, although three fetuses with hematocrits below 15% showed no signs of hydrops. In patients followed with serial sonography, hydramnios was noted as the earliest sonographic abnormality in six of nine pregnancies. All six fetuses were anemic (hematocrit 14-26%) and required transfusion. However, in three pregnancies where the fetus was anemic (hematocrit 22%), there was no hydramnios or other sonographic abnormality. Increased placental thickness was observed in association with fetal hydrops and a hematocrit below 15% in four cases, as well as in three other cases with fetal hematocrit between 16-29% but no fetal hydrops. Measurements of umbilical vein diameter provided no useful information because no increase was observed in these measurements, even in pregnancies with advanced fetal disease evidenced by hydrops.