A methodology for using Lambda phages as a proxy for pathogen transmission in hospitals.

BACKGROUND: One major concern in hospitalized patients is acquiring infections from pathogens borne on surfaces, patients, and healthcare workers (HCWs). Fundamental to controlling healthcare-associated infections is identifying the sources of pathogens, monitoring the processes responsible for their transmission, and evaluating the efficacy of the procedures employed for restricting their transmission. AIM: To present a method using the bacteriophage Lambda (λ) to achieve these ends. METHODS: Defined densities of multiple genetically marked λ phages were inoculated at known hotspots for contamination on high-fidelity mannequins. HCWs then entered a pre-sanitized simulated hospital room and performed a series of patient care tasks on the mannequins. Sampling occurred on the scrubs and hands of the HCWs, as well as previously defined high-touch surfaces in hospital rooms. Following sampling, the rooms were decontaminated using procedures demonstrated to be effective. Following the conclusion of the simulation, the samples were tested for the presence, identity, and densities of these λ phages. FINDINGS: The data generated enabled the determination of the sources and magnitude of contamination caused by the breakdown of established infection prevention practices by HCWs. This technique enabled the standardized tracking of multiple contaminants during a single episode of patient care. Unlike other biological surrogates, λ phages are susceptible to common hospital disinfectants, and allow for a more accurate evaluation of pathogen transmission. CONCLUSION: Whereas our application of these methods focused on healthcare-associated infections and the role of HCW behaviours in their spread, these methods could be employed for identifying the sources and sites of microbial contamination in other settings.

Mental health in the veterinary profession: an individual or organisational focus?

The veterinary profession is experiencing a shortage of veterinarians, with attrition recognised as a substantial contributor. Research has also indicated increased levels of mental ill health and alarming suicide rates in practitioners. The primary aim of this study was to investigate the impact of eleven modifiable workplace factors on mental health outcomes, job appreciation and intention to leave the veterinary profession. The second aim was to ascertain whether workplace factors influence mental health outcomes after controlling for individual resilience. An online survey was completed by 73 practising Australian veterinarians. Unfavourable workplace factors correlated with adverse outcomes including depression, stress, reduced job appreciation and increased likelihood of leaving both the role and the profession. Workplace factors remained linked with the outcomes of job appreciation, depression and stress whilst controlling for practitioner resilience. Job appreciation was a significant predictor of intention to leave both the current role and the profession. Via multiple linear regression, two categories were identified as associated with improved psychological outcomes and job appreciation. These were workplace factors that represent breaks from workload and control or decision latitude in the workplace. Whilst resilience represents a key area for intervention, workplace factors potentially represent an easier-to-modify area for intervention.

Can the Hartree-Fock kinetic energy exceed the exact kinetic energy?

The Hartree-Fock (HF) approximation has been an important tool for quantum-chemical calculations since its earliest appearance in the late 1920s and remains the starting point of most single-reference methods in use today. Intuition suggests that the HF kinetic energy should not exceed the exact kinetic energy; but no proof of this conjecture exists, despite a near century of development. Beginning from a generalized virial theorem derived from scaling considerations, we derive a general expression for the kinetic energy difference that applies to all systems. For any atom or ion, this trivially reduces to the well-known result that the total energy is the negative of the kinetic energy and, since correlation energies are never positive, proves the conjecture in this case. Similar considerations apply to molecules at their equilibrium bond lengths. We use highly precise calculations on Hooke's atom (two electrons in a parabolic well) to test the conjecture in a nontrivial case and to parameterize the difference between density functional and HF quantities, but find no violations of the conjecture.

Fine-regolith production on asteroids controlled by rock porosity.

Spacecraft missions have observed regolith blankets of unconsolidated subcentimetre particles on stony asteroids1-3. Telescopic data have suggested the presence of regolith blankets also on carbonaceous asteroids, including (101955) Bennu4 and (162173) Ryugu5. However, despite observations of processes that are capable of comminuting boulders into unconsolidated materials, such as meteoroid bombardment6,7 and thermal cracking8, Bennu and Ryugu lack extensive areas covered in subcentimetre particles7,9. Here we report an inverse correlation between the local abundance of subcentimetre particles and the porosity of rocks on Bennu. We interpret this finding to mean that accumulation of unconsolidated subcentimetre particles is frustrated where the rocks are highly porous, which appears to be most of the surface10. The highly porous rocks are compressed rather than fragmented by meteoroid impacts, consistent with laboratory experiments11,12, and thermal cracking proceeds more slowly than in denser rocks. We infer that regolith blankets are uncommon on carbonaceous asteroids, which are the most numerous type of asteroid13. By contrast, these terrains should be common on stony asteroids, which have less porous rocks and are the second-most populous group by composition13. The higher porosity of carbonaceous asteroid materials may have aided in their compaction and cementation to form breccias, which dominate the carbonaceous chondrite meteorites14.

Lessons Learned: A Process Evaluation of the Rural Elder Awareness of Medication Safety (REAMS) Program.

This process evaluation of the Rural Elder Awareness of Medication Safety (REAMS) program provided identification of successful and unsuccessful elements along with barriers to and facilitators of this home-based pilot program. The REAMS program was developed to assist rural older adults aged >65 years and community health care organizations with strategies to improve health literacy related to medications. Recruitment of older adults, rurality of the program's setting, time constraints, and the onset of the COVID-19 pandemic were the greatest barriers. The collaborative relationship developed with community health care partners was the greatest facilitator. This relationship promoted shared ideas and adjustments in program design to achieve the outcome goals. The lessons learned from process evaluation may benefit future researchers or community health promotion planners with designing community-based programs for older adults in rural areas. Future research should focus on expanding recruitment opportunities in acute care, primary care, and home health with the inclusion of all established health care providers in the community. [Journal of Gerontological Nursing, 47(4), 7-12.].

Long-term Overall Survival Outcomes in Patients with Early Stage, Peripherally Located, Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiotherapy in a Non-academic Cancer Centre.

AIMS: To report long-term outcomes of patients treated with stereotactic ablative radiotherapy (SABR) for early stage, peripherally located non-small cell lung cancer. MATERIALS AND METHODS: Data were collected retrospectively between September 2009 and May 2019. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. All patients were treated according to local protocol based on the national UK SABR Consortium guidelines. Risk-adapted treatment schedules were used depending on the size and the location of the tumour (54 Gy in three fractions, 55 Gy in five fractions, 60 Gy in eight fractions or 50 Gy in 10 fractions). Overall survival outcomes were evaluated using the Kaplan-Meier method. RESULTS: In total, 412 patients were included in the analysis. The median age was 76 years (range 48-93 years). Histological confirmation was obtained in 233 cases (56.6%). The median overall survival for all patients was 42.3 months (95% confidence interval 37.3-47.3 months), with 3- and 5-year overall survival of 52.8% and 37.3%, respectively. For biopsy-proven patients (56.6%), 3- and 5-year overall survival was 57.3% and 40.1%, respectively. With respect to overall survival, univariate and multivariate analysis revealed no significant difference in survival by technique (volume-modulated arc therapy versus conformal; three-dimensional computed tomography versus four-dimensional computed tomography), tumour location, smoking status at first contact, pre-treatment tumour stage or pre-treatment standardised uptake value. Survival was poorer for patients who received the 50 Gy in 10 fractions schedule. Treatment was very well tolerated with very low rates of grade 3-4 toxicity (1%). CONCLUSIONS: SABR for peripherally located, medically inoperable non-small cell lung cancer can be safely and effectively implemented in a non-academic institution with appropriate equipment and training. Overall survival outcomes and toxicity rates are comparable with internationally published studies. Patients treated with 50 Gy in 10 fractions had a poorer survival outcome.

Asteroid (101955) Bennu's weak boulders and thermally anomalous equator.

Thermal inertia and surface roughness are proxies for the physical characteristics of planetary surfaces. Global maps of these two properties distinguish the boulder population on near-Earth asteroid (NEA) (101955) Bennu into two types that differ in strength, and both have lower thermal inertia than expected for boulders and meteorites. Neither has strongly temperature-dependent thermal properties. The weaker boulder type probably would not survive atmospheric entry and thus may not be represented in the meteorite collection. The maps also show a high-thermal inertia band at Bennu's equator, which might be explained by processes such as compaction or strength sorting during mass movement, but these explanations are not wholly consistent with other data. Our findings imply that other C-complex NEAs likely have boulders similar to those on Bennu rather than finer-particulate regoliths. A tentative correlation between albedo and thermal inertia of C-complex NEAs may be due to relative abundances of boulder types.

Bright carbonate veins on asteroid (101955) Bennu: Implications for aqueous alteration history.

The composition of asteroids and their connection to meteorites provide insight into geologic processes that occurred in the early Solar System. We present spectra of the Nightingale crater region on near-Earth asteroid Bennu with a distinct infrared absorption around 3.4 micrometers. Corresponding images of boulders show centimeters-thick, roughly meter-long bright veins. We interpret the veins as being composed of carbonates, similar to those found in aqueously altered carbonaceous chondrite meteorites. If the veins on Bennu are carbonates, fluid flow and hydrothermal deposition on Bennu's parent body would have occurred on kilometer scales for thousands to millions of years. This suggests large-scale, open-system hydrothermal alteration of carbonaceous asteroids in the early Solar System.

Variations in color and reflectance on the surface of asteroid (101955) Bennu.

Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. Here we present multispectral images (0.44 to 0.89 micrometers) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials does not simply progress from red to blue (or vice versa). Instead, freshly exposed, redder surfaces initially brighten in the near-ultraviolet region (i.e., become bluer at shorter wavelengths), then brighten in the visible to near-infrared region, leading to Bennu's moderately blue average color. Craters indicate that the time scale of these color changes is ~105 years. We attribute the reflectance and color variation to a combination of primordial heterogeneity and varying exposure ages.

Value and learning from carer involvement in a cluster randomised controlled trial and process evaluation - Organising Support for Carers of Stroke Survivors (OSCARSS).

BACKGROUND: Patient, Carer and Public Involvement (PCPI) should be embedded in health care research. Delivering PCPI can be challenging, but even when PCPI is carried out it is rarely reported resulting in lost opportunities for learning. This paper aims to describe PCPI in the OSCARSS study, a pragmatic-cluster randomised controlled trial with an embedded economic and process evaluation. METHODS: A carer research user group (RUG) co-developed OSCARSS to evaluate how to best deliver support to caregivers of stroke survivors. The PCPI activity involved regular meetings and preparatory work, from the initial conceptualisation of the study through to dissemination. Written reports, structured group discussions and individual interviews were carried out with the RUG and researchers to capture the added value and learning. This paper was co-authored by two of the RUG members with contributions from the wider RUG and researchers. RESULTS: The core six members of the caregiver RUG attended the majority of the meetings alongside three researchers, one of whom was the co-chief investigator. PCPI was instrumental in changing many aspects of the research protocol, design and delivery and contributed to dissemination and sharing of good practice. There were challenges due to the emotional toll when PCPI members shared their stories and the extensive time commitment. Positive experiences of learning and fulfilment were reported by the individual researchers and PCPI members. Wider organisational administrative and financial support facilitated the PCPI. The researchers' existing positive regard for PCPI and the clear focus of the group were key to the successful co-design of this research. CONCLUSIONS: The value and learning from the PCPI collaborative work with the researchers was of benefit to the study and the individuals involved. Specific PCPI influences were a challenge to pinpoint as successful co-design meant the researchers' and carers' contributions were intertwined and decision-making shared.

Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.

BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Shape of (101955) Bennu indicative of a rubble pile with internal stiffness.

The shapes of asteroids reflect interplay between their interior properties and the processes responsible for their formation and evolution as they journey through the Solar System. Prior to the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission, Earth-based radar imaging gave an overview of (101955) Bennu's shape. Here, we construct a high-resolution shape model from OSIRIS-REx images. We find that Bennu's top-like shape, considerable macroporosity, and prominent surface boulders suggest that it is a rubble pile. High-standing, north-south ridges that extend from pole to pole, many long grooves, and surface mass wasting indicate some low levels of internal friction and/or cohesion. Our shape model indicates that, similar to other top-shaped asteroids, Bennu formed by reaccumulation and underwent past periods of fast spin leading to its current shape. Today, Bennu might follow a different evolutionary pathway, with interior stiffness permitting surface cracking and mass wasting.

Pliocene and Eocene provide best analogs for near-future climates.

As the world warms due to rising greenhouse gas concentrations, the Earth system moves toward climate states without societal precedent, challenging adaptation. Past Earth system states offer possible model systems for the warming world of the coming decades. These include the climate states of the Early Eocene (ca. 50 Ma), the Mid-Pliocene (3.3-3.0 Ma), the Last Interglacial (129-116 ka), the Mid-Holocene (6 ka), preindustrial (ca. 1850 CE), and the 20th century. Here, we quantitatively assess the similarity of future projected climate states to these six geohistorical benchmarks using simulations from the Hadley Centre Coupled Model Version 3 (HadCM3), the Goddard Institute for Space Studies Model E2-R (GISS), and the Community Climate System Model, Versions 3 and 4 (CCSM) Earth system models. Under the Representative Concentration Pathway 8.5 (RCP8.5) emission scenario, by 2030 CE, future climates most closely resemble Mid-Pliocene climates, and by 2150 CE, they most closely resemble Eocene climates. Under RCP4.5, climate stabilizes at Pliocene-like conditions by 2040 CE. Pliocene-like and Eocene-like climates emerge first in continental interiors and then expand outward. Geologically novel climates are uncommon in RCP4.5 (<1%) but reach 8.7% of the globe under RCP8.5, characterized by high temperatures and precipitation. Hence, RCP4.5 is roughly equivalent to stabilizing at Pliocene-like climates, while unmitigated emission trajectories, such as RCP8.5, are similar to reversing millions of years of long-term cooling on the scale of a few human generations. Both the emergence of geologically novel climates and the rapid reversion to Eocene-like climates may be outside the range of evolutionary adaptive capacity.

Influences on use of hand moisturizers in nurses.

Background: Nurses are at high risk of hand dermatitis. Regular hand moisturizing can prevent dermatitis, but nurses' use of hand moisturizers is suboptimal. Aims: To establish (i) what beliefs about hand dermatitis and hand moisturizer use are associated with hand moisturizer use by nurses at home and at work and (ii) if hand moisturizer use behaviours in nurses are associated with the prevalence of hand dermatitis. Methods: We used a questionnaire to investigate nurses' knowledge, beliefs and behaviours regarding hand dermatitis and use of hand moisturizers. Results: The response rate was 55/65 (85%). Forty-two (76%) participants agreed that applying hand moisturizers reduced the risk of dermatitis, and 53 (96%) agreed that dermatitis increased the risk of skin carrying pathogenic organisms. Frequent moisturizer application was associated with beliefs that it was part of the nurse's role to apply hand creams, a belief that they had had training in the use of moisturizers and believing that patients approved of them moisturizing their hands. Conclusions: Hand moisturizer use by nurses can be improved by enhancing their beliefs that it is part of their professional role to apply hand cream regularly.

Population levels of wellbeing and the association with social capital.

BACKGROUND: This research investigates wellbeing at the population level across demographic, social and health indicators and assesses the association between wellbeing and social capital. METHOD: Data from a South Australian monthly chronic disease/risk factor surveillance system of randomly selected adults (mean age 48.7 years; range 16-99) from 2014/5 (n = 5551) were used. Univariable analyses compared wellbeing/social capital indicators, socio-demographic, risk factors and chronic conditions. Multi-nominal logistic regression modelling, adjusting for multiple covariates was used to simultaneously estimate odds ratios for good wellbeing (reference category) versus neither good nor poor, and good wellbeing versus poor wellbeing. RESULTS: 48.6% were male, mean age 48.7 (sd 18.3), 54.3% scored well on all four of the wellbeing indicators, and positive social capital indicators ranged from 93.1% for safety to 50.8% for control over decisions. The higher level of social capital corresponded with the good wellbeing category. Modeling showed higher odds ratios for all social capital variables for the lowest level of wellbeing. These higher odds ratios remained after adjusting for confounders. CONCLUSIONS: The relationship between wellbeing, resilience and social capital highlights areas for increased policy focus.

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported. Here we report on the identification of a novel PALB2 variant, c.104T>C (p.L35P), that segregates in a family with a strong history of breast cancer. Functional analyses showed that L35P abrogates the PALB2-BRCA1 interaction and completely disables its abilities to promote HR and confer resistance to platinum salts and PARP inhibitors. Whole-exome sequencing of a breast cancer from a c.104T>C carrier revealed a second, somatic, truncating mutation affecting PALB2, and the tumor displays hallmark genomic features of tumors with BRCA mutations and HR defects, cementing the pathogenicity of L35P. Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development. Our findings establish L35P as the first pathogenic missense mutation in PALB2 and directly demonstrate the requirement of the PALB2-BRCA1 interaction for breast cancer suppression.

An intensive personalised support approach to treating individuals with psychosis and co-morbid mild intellectual disability.

OBJECTIVES: To evaluate the clinical benefits and associated cost effectiveness of an intensive personalised support (IPS) approach for clients suffering from psychosis and co-morbid mild intellectual disability (ID). METHOD: Four individuals with a psychotic disorder and co-morbid mild ID participated in an 18-month IPS rehabilitative intervention. Biopsychosocial measures were used to evaluate clinical effectiveness. A cost analysis was undertaken to examine the cost effectiveness of the intervention. RESULTS: Reductions in psychopathology including anxiety symptoms were noted in all individuals. In addition, increased functioning and quality of life were demonstrated in all cases. Overall cost reductions were noted in inpatient care, accommodation and legal/emergency expenses. CONCLUSION: The IPS approach was clinically effective particularly in addressing individual's psychosocial needs, psychological functioning, daily living skills and overall quality of life. Costs had decreased for three of the four individuals, ranging from a 17% to 46% savings. The findings highlight that the intervention was cost effective in most cases at this early stage. However, further research is necessary in order to ascertain if cost savings occur over time.

Multi-parameter regression survival modeling: An alternative to proportional hazards.

It is standard practice for covariates to enter a parametric model through a single distributional parameter of interest, for example, the scale parameter in many standard survival models. Indeed, the well-known proportional hazards model is of this kind. In this article, we discuss a more general approach whereby covariates enter the model through more than one distributional parameter simultaneously (e.g., scale and shape parameters). We refer to this practice as "multi-parameter regression" (MPR) modeling and explore its use in a survival analysis context. We find that multi-parameter regression leads to more flexible models which can offer greater insight into the underlying data generating process. To illustrate the concept, we consider the two-parameter Weibull model which leads to time-dependent hazard ratios, thus relaxing the typical proportional hazards assumption and motivating a new test of proportionality. A novel variable selection strategy is introduced for such multi-parameter regression models. It accounts for the correlation arising between the estimated regression coefficients in two or more linear predictors-a feature which has not been considered by other authors in similar settings. The methods discussed have been implemented in the mpr package in R.