The association of environmental factors with neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia (ALL).

PURPOSE: To investigate the association of environmental factors, rehabilitation services during therapy and socioeconomic status (SES - insurance type), with neurocognitive outcomes at the end of therapy for survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Survivors (n = 236) treated on the St. Jude Total Therapy Study 16 completed end of therapy testing with performance measures (IQ, attention, processing speed, fine motor skills, academics) and caregiver ratings (attention, executive function, adaptive skills). Environmental factors were abstracted from the medical record. RESULTS: Distribution of sex (47.3% female, p = 0.399), treatment arm (45.5% low risk, 54.5% standard/high risk p = 0.929), insurance type (47.7% private, 52.3% public/none, p = 0.117), and mean age at diagnosis (7.7 vs. 6.8 years, p = 0.143) were similar for groups with (n = 110; 46.6%) and without (n = 126; 53.6%) rehabilitation services during therapy. Compared to those without rehabilitation, the rehabilitation group (n = 110; 46.4%) had more caregiver reported problems with attention (Z = -0.28 vs. 0.43, p = 0.022), executive function (Z = -0.50 vs. -0.08, p = 0.003), and adaptive skills (Z = -0.41 vs.-0.13, p = 0.031). Among the rehabilitation group, there was no difference in outcomes by insurance status. Among those without rehabilitation, those with public insurance had worse neurocognitive outcomes than those with private insurance in IQ (Z = -0.04 vs. -0.45, p = 0.0115), processing speed (Z = -0.10 vs. -0.75, p = 0.0030), reading (Z = 0.18 vs. -0.59, p < 0.0001), and math (Z = -0.04 vs. -0.50, p = 0.0021). CONCLUSION: Participation in rehabilitation services during early intensive therapy is associated with end of therapy caregiver-reported neurocognitive outcomes in daily life.

Clinical, Radiologic, and Histopathologic Features that Distinguish a Pigmented Plexiform Neurofibroma from a Congenital Melanocytic Nevus.

A 13-year-old Hispanic boy with no significant medical etymology presented with a chief complaint of widespread brown macules and patches. He had a large and evenly pigmented brown patch, with a centrally located 2.2 cm × 1.2 cm soft and darkly pigmented plaque, which became more apparent with tension applied to the surrounding skin (Figure 1). The patient's mother stated that the plaque was present since birth and had increased in size over time. The clinical differential diagnoses included a congenital melanocytic nevus (CMN), a large café au lait macule (CALM), and a Becker's nevus with a congenital smooth muscle hamartoma.

Effect of altering milking interval when milking 3 times in 2 days on milk and component yields in pasture-based dairy systems.

Dairy farmers face challenges attracting and retaining staff, partly due to the difficulty meeting the desires of the modern workforce. These include flexible work hours and regular time off. The task of milking fundamentally affects the ability of dairy farmers to meet these desires. Milking contributes to a large proportion of the hours spent working on dairy farms. The number of milkings (milking frequency) and their timing (milking interval) within a day influence the number of hours spent milking and what time in the day they occur. Milking 3 times in 2 d (3-in-2) reduces the amount of time spent milking compared with milking twice a day (TAD), without reducing milk yield as much as milking once a day (OAD). However, long intervals between 3-in-2 milkings can still lead to a long workday if farmers are expected to work between milkings. The objective of this study was to determine the effect of milking interval within a 3-in-2 milking frequency on milk yield and composition at 2 stages of lactation and compare these with OAD and TAD milking. Cows (n = 200) were milked in 5 groups of 40 at 3 intervals of 3-in-2: 8-20-20 h, 10-19-19 h, and 12-18-18 h, along with 24 h (OAD), and 10 and 14 h (TAD), for 6 wk at early lactation (mean 24 d in milk ± 7 d, SD) and again at mid lactation (mean 136 d in milk ± 18 d). Milk yields were recorded at each milking and milk samples collected weekly to determine composition. At both early and mid lactation there were no significant differences in milk, fat, protein, or lactose yields between the three 3-in-2 intervals. Cows milked 3-in-2 produced 8% less milk than cows milked TAD and 14% more than cows milked OAD, with smaller differences observed at mid lactation between TAD and 3-in-2. For a 3-in-2 milking frequency, a shorter milking interval can be implemented on the days when cows are milked twice. This may allow farmers to shorten the working day when using 3-in-2, without compromising milk or component yields.

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.

Exploring postgraduate epidemiology competencies: Preparing our students for a post-COVID world.

OBJECTIVE: This research sought consensus from both experts and graduates on postgraduate epidemiology competencies. METHODS: In 2021, a two-round online survey using a modified Delphi method was undertaken exploring competencies across six domains. Focus groups were conducted with recent postgraduate epidemiology graduates to assess their viewpoints on learning experiences and employability. RESULTS: Forty-one experts participated in the first Delphi round. Nineteen factors reached consensus (>70% agreement) for importance and feasibility after two survey rounds in the following domains: general epidemiologic methods/concepts (n=8/13), advanced analytic/statistical skills (n=2/7), applied epidemiology/specialised fields (n=1/4), professional/transferrable skills (n=5/14), general public health knowledge/skills (n=2/4), independent research and work-integrated learning (n=1/3). Nine graduates participated in focus groups. A main theme was the substantial value gained in undertaking a dissertation, acknowledging its benefit for applying research skills and for networking opportunities. CONCLUSIONS: To ensure that high-quality epidemiological research and practice continues, we need consensus on the set of essential skills required of graduating students. IMPLICATIONS FOR PUBLIC HEALTH: Competencies for postgraduate epidemiology students require periodic review to safeguard a workforce that can meet emerging challenges and work across academia, research, policy, and practice.

Behavioural responses of a large, heat-sensitive mammal to climatic variation at multiple spatial scales.

Climate warming creates energetic challenges for endothermic species by increasing metabolic and hydric costs of thermoregulation. Although endotherms can invoke an array of behavioural and physiological strategies for maintaining homeostasis, the relative effectiveness of those strategies in a climate that is becoming both warmer and drier is not well understood. In accordance with the heat dissipation limit theory which suggests that allocation of energy to growth and reproduction by endotherms is constrained by the ability to dissipate heat, we expected that patterns of habitat use by large, heat-sensitive mammals across multiple scales are critical for behavioural thermoregulation during periods of potential heat stress and that they must invest a large portion of time to maintain heat balance. To test our predictions, we evaluated mechanisms underpinning the effectiveness of bed sites for ameliorating daytime heat loads and potential heat stress across the landscape while accounting for other factors known to affect behaviour. We integrated detailed data on microclimate and animal attributes of moose Alces alces, into a biophysical model to quantify costs of thermoregulation at fine and coarse spatial scales. During summer, moose spent an average of 67.8% of daylight hours bedded, and selected bed sites and home ranges that reduced risk of experiencing heat stress. For most of the day, shade could effectively mitigate the risk of experiencing heat stress up to 10°C, but at warmer temperatures (up to 20°C) wet soil was necessary to maintain homeostasis via conductive heat loss. Consistent selection across spatial scales for locations that reduced heat load underscores the importance of the thermal environment as a driver of behaviour in this heat-sensitive mammal. Moose in North America have long been characterized as riparian-obligate species because of their dependence on woody plant species for food. Nevertheless, the importance of dissipating endogenous heat loads conductively through wet soil suggests riparian habitats also are critical thermal refuges for moose. Such refuges may be especially important in the face of a warming climate in which both high environmental temperatures and drier conditions will likely exacerbate limits to heat dissipation, especially for large, heat-sensitive animals.

Health service COVID-19 wellbeing and support initiatives: a mixed-methods evaluation.

BACKGROUND: Health services implemented a range of initiatives during the COVID-19 pandemic to support employee wellbeing and assist employees to manage the professional and personal challenges they experienced. However, it is not known if such initiatives were acceptable to employees or met their needs. AIMS: To evaluate the wellbeing and support initiatives implemented at an Australian health service during the COVID-19 pandemic from the perspectives of employees (both users and non-users) and key stakeholders. METHODS: A mixed-methods design (survey, interviews and data audit) to investigate employees' and key stakeholders' perceptions, experiences and use of the wellbeing and support initiatives implemented at a large tertiary metropolitan health service in Melbourne, Australia. RESULTS: Ten employees participated in an interview and 907 completed a survey. The initiatives were well used and appreciated by staff. There was no significant difference in the proportion of clinical staff who had used the initiatives compared to non-clinical staff (44% versus 39%; P=0.223). Survey respondents reported the initiatives improved their mental health (n = 223, 8%), ability to cope with COVID-19 related stress and anxiety (n = 206, 79%), do their work (n = 200, 77%) and relationships with colleagues (n = 174, 67%). Staff would like many of the initiatives (with some modifications) to continue after the COVID-19 pandemic. CONCLUSIONS: The findings suggest a high level of staff satisfaction with the implemented wellbeing and support initiatives, and confirm the need for, and importance of, developing and implementing initiatives to support health service staff during outbreaks of infectious diseases such as the COVID-19 pandemic.

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

Changes to objective structured clinical examinations (OSCE) at Australian medical schools in response to the COVID-19 pandemic.

INTRODUCTION: Objective Structured Clinical Examinations (OSCE) are used to assess clinical skills. We investigated how exit OSCEs changed in Australian medical schools in response to the COVID-19 pandemic. MATERIALS AND METHODS: The lead ACCLAiM assessment academic from 12 eligible Australian medical school members of the Australian Collaboration for Clinical Assessment in Medicine (ACCLAiM) received a 45-item semi-structured online questionnaire. RESULTS: All schools (12/12) responded. Exit OSCEs were not used by one school in 2019, and 3/11 schools in 2020. Of eight remaining schools, four reduced station numbers and testing time. The minimum OSCE testing time decreased from 64 min in 2019 to 54 min in 2020. Other modifications included: a completely online 'e-OSCE' (n = 1); hybrid delivery (n = 4); stations using: videos of patient encounters (n = 3), telephone calls (n = 2), skill completion without face-to-face patient encounters (n = 3). The proportion of stations involving physical examination reduced from 33% to 17%. Fewer examiners were required, and university faculty staff formed a higher proportion of examiners. CONCLUSIONS: All schools changed their OSCEs in 2020 in response to COVID-19. Modifications varied from reducing station numbers and changing delivery methods to removing OSCE and complete assessment re-structuring. Several innovative methods of OSCE delivery were implemented to preserve OSCE validity and reliability whilst balancing feasibility.

Diverse clinical and social circumstances: developing patient-centred care for DR-TB patients in South Africa.

OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.

OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.

Longitudinal associations between exposure to anesthesia and neurocognitive functioning in pediatric medulloblastoma.

AIM: To examine whether anesthesia exposure is associated with neurocognitive decline in pediatric medulloblastoma. METHODS: Patients were treated at St. Jude Children's Research Hospital and completed ≥2 protocol-directed neurocognitive assessments (n = 107) as part of a multisite clinical trial for pediatric medulloblastoma (NCT00085202). Patients received risk-adapted craniospinal photon irradiation, followed by four cycles of high-dose chemotherapy and stem cell rescue. Neurocognitive testing was completed at study baseline (after surgery and <2 weeks of starting radiation therapy) and annually for 5 years. Data on anesthesia exposure during treatment was abstracted from medical records. RESULTS: Patients were 10.2 years at diagnosis on average (SD = 4.5; 37% female, 73% average-risk). Mean cumulative anesthesia duration was 20.4 h (SD = 15.2; range 0.7-55.6 h). In the overall group, longer anesthesia duration was associated with greater declines in IQ (Estimate = -0.08, P < 0.001), attention (Estimate = -0.10, P < .001) and processing speed (Estimate = -0.13, P < 0.001). Similar results were shown in subgroups of patients who were <7 years at diagnosis (IQ = -0.14, P = 0.027; Attention = -0.25: P = 0.011), ≥7 years at diagnosis (Attention = -0.07, P = 0.039; Processing Speed = -0.08, P = 0.022), treated for high-risk disease (IQ = -0.09, P = 0.024; Attention = -0.11, P = 0.034; Processing Speed = -0.13, P = 0.001), or treated for average-risk disease (IQ = -0.05, P = .022; Attention = -0.08, P = 0.011; Processing Speed = -0.10, P < 0.001). CONCLUSION: Greater anesthesia exposure is a risk factor for clinically significant neurocognitive decline, in addition to factors of age at diagnosis and treatment risk arm. This result is notable as there are evidence-based strategies that can limit the need for anesthesia. Limiting anesthesia exposure, as feasible, may mitigate neurocognitive late effects, and thus, improve quality of life for survivors.

Patterns and trends in lake concentrations of dissolved organic carbon in a landscape recovering from environmental degradation and widespread acidification.

Concentrations of dissolved organic carbon (DOC) have increased in lakes throughout North America and Europe over the last three decades. Recovery from acid deposition and climate change have both been postulated as the primary mechanisms for the increase in DOC. To provide a clearer insight into the mechanisms responsible for increasing DOC we evaluated changes in lake and peat porewater chemistry collected in an area of approximately 33,000 km2 surrounding Sudbury, Ontario, a region undergoing dramatic recovery from acidic deposition. DOC concentrations varied considerably among the 44 lakes and over time (samples annually from 1981 to 2018), but the Sens Slope value showed a strong increase in lake DOC concentration over time, at 0.05 mg/ L y-1 (p < 0.001) that was related to increasing pH [0.03 units y-1, p < 0.001] and decreasing lake SO4 concentration [-0.24 mg/ L y-1; p < 0.001], but showed no relationship with temperature or precipitation. Similar strong relationships between DOC and pH (positive) and SO4 (negative) were observed in 18 peatlands sampled in the region. In a spatial analysis of 82 lakes sampled in 2018, concentrations of DOC in lakes were highest in flatter catchments with a greater wetland area, suggesting that wetlands are a major source of DOC in lakes. Optical properties of DOC obtained from extracts of wetland and upland soils at 6 catchments could be distinguished, primarily due to upland litter extracts having distinct optical properties from mineral soils or wetland soils. Optical properties of DOC in lakes however were inconsistent with those measured in soil extracts indicating that they are not useful for distinguishing DOC sources in these lakes. A predictive model was developed to explain DOC trends within Sudbury lakes using a stepwise linear regression combined with hierarchical partitioning to confirm the most influential processes on DOC. Almost 50% of the variability in DOC change in the 44 lakes was explained by the magnitude in lake pH change, catchment size and catchment sparse tree cover showing that recovery from acidic deposition is overwhelmingly responsible for increasing DOC in Sudbury lakes.

High-throughput analysis suggests differences in journal false discovery rate by subject area and impact factor but not open access status.

BACKGROUND: A low replication rate has been reported in some scientific areas motivating the creation of resource intensive collaborations to estimate the replication rate by repeating individual studies. The substantial resources required by these projects limits the number of studies that can be repeated and consequently the generalizability of the findings. We extend the use of a method from Jager and Leek to estimate the false discovery rate for 94 journals over a 5-year period using p values from over 30,000 abstracts enabling the study of how the false discovery rate varies by journal characteristics. RESULTS: We find that the empirical false discovery rate is higher for cancer versus general medicine journals (p = 9.801E-07, 95% CI: 0.045, 0.097; adjusted mean false discovery rate cancer = 0.264 vs. general medicine = 0.194). We also find that false discovery rate is negatively associated with log journal impact factor. A two-fold decrease in journal impact factor is associated with an average increase of 0.020 in FDR (p = 2.545E-04). Conversely, we find no statistically significant evidence of a higher false discovery rate, on average, for Open Access versus closed access journals (p = 0.320, 95% CI - 0.015, 0.046, adjusted mean false discovery rate Open Access = 0.241 vs. closed access = 0.225). CONCLUSIONS: Our results identify areas of research that may need additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical false discovery rate across other subject areas and characteristics of published research.

Feed acidification and steam-conditioning temperature influence nutrient utilization in broiler chickens fed wheat-based diets.

Two experiments were conducted to examine the effects of conditioning temperature (CT) and the interactive influence of feed acidification (FA) and CT on the performance, coefficient of apparent ileal digestibility (CAID) of nitrogen (N), starch, fat calcium (Ca) and phosphorus (P), and AME in broilers. In both experiments, each treatment was randomly allocated to 6 cages (8 birds per cage) and fed from 1 to 21 D posthatch. In experiment 1, the effect of CT was evaluated using a wheat-based diet at 3 CT: unconditioned, conditioned at 60°C or 90°C. All the diets by-passed the pellet press and collected in mash form. Birds fed the diet conditioned at 90°C consumed more (P < 0.05) feed and tended (P = 0.087) to have higher feed per gain (F:G) than those fed the unconditioned diet but similar to those fed the diet conditioned at 60°C. A tendency was noted for CT to affect the CAID of N (P = 0.071) and starch (P = 0.093), with reduced digestibility values in the diet conditioned at 90°C. Conditioning at 90°C resulted in lower (P < 0.05) AME. In experiment 2, three inclusions of an acidifier (0.0, 7.0, and 10 g/kg) and 2 CT of 60°C and 90°C were evaluated in a 3 × 2 factorial arrangement of treatments using pelleted diets. Neither the main effects nor the interaction between acidifier addition and CT was significant for weight gain, feed intake, and F:G. The FA increased (P < 0.05) the CAID of N, fat, and P at both inclusion levels and of starch at 10 g/kg. Conditioning at 90°C reduced (P < 0.05) the CAID of starch, fat, and Ca, regardless of FA level. Overall, the present data showed that the application of high CT for broiler feed manufacture can impair nutrient utilization and, consequently the feed efficiency in broilers. Feed acidification imparts some benefits to nutrient digestibility in broilers fed pelleted wheat-based diets.

Experiences of using the i-PARIHS framework: a co-designed case study of four multi-site implementation projects.

BACKGROUND: The integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework is an implementation framework that has been developed and refined over the last 20 years. Its underlying philosophy is that implementing research into healthcare practice is complex, unpredictable and non-linear which therefore requires a flexible and responsive approach to implementation. Facilitation is recognized as the central ingredient of this approach, and i-PARIHS now provides a Facilitation Guide with associated tools. This multiple case study of four implementation projects explored how the i-PARIHS framework has been practically operationalized by diverse implementation project teams. METHODS: A co-design approach was used to elicit the experiences of four implementation project teams who used the i-PARIHS framework to guide their implementation approach. We conducted the established co-design steps of (i) setting up for success, (ii) gathering the experience, and (iii) understanding the experience. In particular we explored teams' approaches to setting up their projects; why and how they used the i-PARIHS framework and what they learnt from the experience. RESULTS: We found both commonalities and differences in the use of i-PARIHS across the four implementation projects: (i) all the projects used the Facilitation Checklist that accompanies i-PARIHS as a starting point, (ii) the projects differed in how facilitation was carried out, (iii) existing tools were adapted for distinct phases: pre-implementation, during implementation, and post-implementation stages; and (iv) project-specific tools were often developed for monitoring implementation activities and fidelity. CONCLUSIONS: We have provided a detailed overview of how current users of i-PARIHS are operationalising the framework, which existing tools they are using or adapting to use, and where they have needed to develop new tools to best utilise the framework. Importantly, this study highlights the value of existing tools from the published i-PARIHS Facilitation Guide and provides a starting point to further refine and add to these tools within a future Mobilising Implementation of i-PARIHS (or "Mi-PARIHS") suite of resources. Specifically, Mi-PARIHS might include more explicit guidance and/or tools for developing a structured implementation plan and monitoring fidelity to the implementation plan, including recording how strategies are tailored to an evolving context.

Drug-resistant tuberculosis patient care journeys in South Africa: a pilot study using routine laboratory data.

SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.

Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches.

The epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. 3D in vitro cultures of human primary epithelial cells, called organoids, have become a key model to study the functions of Paneth cells and goblet cells in normal and diseased conditions. Advances in these models include the ability to skew differentiation to particular lineages, providing a useful tool to study cell type specific function/dysfunction in the context of the epithelium. Here, we use comprehensive profiling of mRNA, microRNA and long non-coding RNA expression to confirm that Paneth cell and goblet cell enrichment of murine small intestinal organoids (enteroids) establishes a physiologically accurate model. We employ network analysis to infer the regulatory landscape altered by skewing differentiation, and using knowledge of cell type specific markers, we predict key regulators of cell type specific functions: Cebpa, Jun, Nr1d1 and Rxra specific to Paneth cells, Gfi1b and Myc specific for goblet cells and Ets1, Nr3c1 and Vdr shared between them. Links identified between these regulators and cellular phenotypes of inflammatory bowel disease (IBD) suggest that global regulatory rewiring during or after differentiation of Paneth cells and goblet cells could contribute to IBD aetiology. Future application of cell type enriched enteroids combined with the presented computational workflow can be used to disentangle multifactorial mechanisms of these cell types and propose regulators whose pharmacological targeting could be advantageous in treating IBD patients with Crohn's disease or ulcerative colitis.

Quantum Bath Control with Nuclear Spin State Selectivity via Pulse-Adjusted Dynamical Decoupling.

Dynamical decoupling (DD) is a powerful method for controlling arbitrary open quantum systems. In quantum spin control, DD generally involves a sequence of timed spin flips (π rotations) arranged to either average out or selectively enhance coupling to the environment. Experimentally, errors in the spin flips are inevitably introduced, motivating efforts to optimize error-robust DD. Here we invert this paradigm: by introducing particular control "errors" in standard DD, namely, a small constant deviation from perfect π rotations (pulse adjustments), we show we obtain protocols that retain the advantages of DD while introducing the capabilities of quantum state readout and polarization transfer. We exploit this nuclear quantum state selectivity on an ensemble of nitrogen-vacancy centers in diamond to efficiently polarize the ^{13}C quantum bath. The underlying physical mechanism is generic and paves the way to systematic engineering of pulse-adjusted protocols with nuclear state selectivity for quantum control applications.

Implementation of government-directed policy in the hospital setting: a modified Delphi study.

BACKGROUND: In the last 20 years governments have sought to introduce policy that improves the quality of care provided in hospitals, yet little research has been done to understand how these policies are implemented, factors that affect the implementation process or what should be considered by decision-makers during policy development or implementation planning. Experts with real-life experience in the introduction and implementation of policy are best placed to provide valuable insight into practical issues that affect implementation and the associated outcomes of these policies. METHODS: A modified Delphi study of experts in hospital policy development and implementation was undertaken to investigate factors influencing the implementation of government-directed policy in the hospital setting. This study built on the findings of two previous studies - a qualitative study of clinician perspectives of policy implementation and a systematic review and meta-synthesis, in which common contextual factors and policy characteristics associated with policy implementation were ascertained. International experts with extensive experience in government-directed policy implementation at global, national, corporate, jurisdictional and organisational levels were asked to provide opinions on predetermined factors and the feasibility of considering these in policy development and implementation planning. Survey design and analysis was guided by the Consolidated Framework for Implementation Research. RESULTS: Eleven experts from four countries and with different health system perspectives participated in the study. Consensus was reached on the importance of all predetermined factors in the first survey round with additional factors for investigation highlighted by participants for examination in subsequent rounds. On study completion, expert consensus was reached on 24 factors of importance; only 20 of these factors reached consensus for feasibility. CONCLUSIONS: Study findings indicated that, whilst there are multiple factors of importance in policy implementation across all Consolidated Framework for Implementation Research domains, some factors, such as establishment of roles and responsibilities for implementation and organisational lines of accountability, are feasible for consideration at a hospital level only. In addition, four factors did not reach consensus in terms of feasibility, indicating that it may not be practical to consider all factors of importance when implementing policy; this has important implications for implementation planning and resource allocation.