An Automated, Dynamic Radiation Oncology Prescription Checking System.

PURPOSE: Despite serving as a critical communication tool, radiation oncology prescriptions are entered manually and prone to error. An automated prescription checking system was developed and implemented to help address this problem. METHODS AND MATERIALS: Rules defining clinically appropriate prescriptions were generated, examining specific types of errors: (1) unapproved dose per fraction for a given disease site; (2) dose per fraction too large for nonstereotactic treatment technique; and (3) dose per fraction too low. With a goal of catching errors as upstream as possible to minimize their propagation, a report was created and ran every 30 minutes to check all newly written or approved prescriptions against the 3 rules. When a prescription violated these rules, an automated email was immediately sent to the prescriber alerting them of the potential error. System performance was continuously monitored and the criteria triggering an alert adjusted to balance error detection against false positives. Alerts leading to prescription amendment were considered true errors. RESULTS: From June 2021 to November 2022, the system checked 24,047 prescriptions. A total of 241 email alerts were triggered, for an average alert rate of 1%. Of the 241 alerts, 198 (82.2%) were unapproved doses per fraction for the disease site, 14 (5.8%) were doses per fraction that were too low, and 29 (12%) were doses too large for nonstereotactic treatment technique. Thirty-one percent of alerts led to a change of prescription, suggesting they were true errors. The baseline rate of erroneous prescription entry was 0.3%. A regression model showed that trainee prescription entry and dose per fraction <150 cGy were significantly associated with true errors. CONCLUSIONS: Given the significant consequences of erroneous prescription entry, which ranged from wasted resources and treatment delays to potentially serious misadministration, there is significant value in implementing automated prescription checking systems in radiation oncology clinics.

Effective practices during emergency school lockdowns: shared experiences of four Australian schools.

This study investigates common features of a set of diverse schools' responses to the initial school lockdown period during the pandemic in 2020, with a focus on practices supporting learning, inclusion and wellbeing. It comprises a collective case study of four Australian schools that were selected based on their reputation for impactful support of students and teachers during the emergency remote teaching period. Methods included interviews and focus groups with school leaders, teachers and students. The schools had widely differing contexts, technology access and student needs. Despite these varied contexts, the findings provided important insights into common practices supporting effective remote teaching. Emerging principles of effective practice illuminate ways forward to mitigate the significant risks accompanying emergency remote teaching, and guide practices in a variety of school contexts.

No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication.

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

Preservation of vascular endothelial repair in mice with diet-induced obesity.

INTRODUCTION: Preservation of structural integrity of the endothelial monolayer and maintenance of endothelial cell function are of critical importance in preventing arterial thrombosis, restenosis and atherosclerosis. Obesity has been intimately linked with endothelial dysfunction, and reports of reduced abundance and functional impairment of circulating progenitor cells in obesity have led to the suggestion that defective endothelial repair contributes to obesity-related cardiovascular disease. METHODS: C57BL/6 mice were fed a high-fat diet for either 3 or 6 months to induce obesity; metabolic phenotyping was then carried out before femoral artery wire injury was performed. Endothelial regeneration was then quantified. Mononuclear cells and myeloid angiogenic cells were cultured and characterized for pro-angiogenic properties. RESULTS: No impairment of endothelial regeneration following mechanical endothelial injury in diet-induced obese mice when compared with chow-fed controls was observed, despite the induction of an adverse metabolic phenotype characterized by glucose intolerance and insulin resistance. Dietary-obese mice had increased numbers of circulating myeloid angiogenic cells, which retained normal functional properties including intact paracrine angiogenic effects. CONCLUSION: Preserved endothelial regeneration despite metabolic dysregulation in dietary obese mice suggests that compensatory mechanisms mitigate the deleterious influence of insulin resistance on endothelial repair in obesity.

Association of prenatal exposure to gestational diabetes with offspring body composition and regional body fat distribution.

The aim of this cohort study was to compare body composition and regional body fat distribution between children exposed (GDM+) or unexposed (GDM-) in utero to gestational diabetes mellitus (GDM) and to investigate the association with the glycaemic and the insulin profile. Data from 56 GDM+ and 30 GDM- were analysed. Height, weight and waist circumference were measured. Total and regional body composition was measured by dual-energy X-ray absorptiometry. Insulin, glucose and HbA1c were obtained from a fasting plasma sample, and the HOMA-IR index was calculated. anova was performed to compare adiposity measures between GDM+ and GDM-. Associations between the glycaemic and insulin profile and adiposity measures were studied using partial Pearson correlations. Mean age was 6.6 ± 2.3 years. Waist circumference, fat mass percentage, android fat mass, android fat mass percentage and android-to-gynoid fat mass ratio were higher among GDM+, and lean mass percentage was lower (P < 0.05). Among GDM+ children, body mass index (BMI) z score, waist circumference, fat mass percentage, android fat mass percentage and android-to-gynoid fat mass ratio were all positively correlated with HbA1C (r = 0.32-0.43, P < 0.05). Prenatal exposure to GDM is associated with increased total and abdominal adiposity. This increased adiposity observed among GDM+ children is associated with an altered glycaemic profile. This study is registered in the Clinical Trials.gov registry (NCT01340924).

Evaluation of bactericidal and anti-biofilm properties of a novel surface-active organosilane biocide against healthcare associated pathogens and Pseudomonas aeruginosa biolfilm.

Healthcare acquired infections (HAI) pose a great threat in hospital settings and environmental contamination can be attributed to the spread of these. De-contamination and, significantly, prevention of re-contamination of the environment could help in preventing/reducing this threat. Goldshield (GS5) is a novel organosilane biocide marketed as a single application product with residual biocidal activity. We tested the hypothesis that GS5 could provide longer-term residual antimicrobial activity than existing disinfectants once applied to surfaces. Thus, the residual bactericidal properties of GS5, Actichlor and Distel against repeated challenge with Staphylococcus aureus ATCC43300 were tested, and showed that GS5 alone exhibited longer-term bactericidal activity for up to 6 days on 316I stainless steel surfaces. Having established efficacy against S. aureus, we tested GS5 against common healthcare acquired pathogens, and demonstrated that, on average, a 1 log10 bactericidal effect was exhibited by GS5 treated surfaces, although biocidal activity varied depending upon the surface type and the species of bacteria. The ability of GS5 to prevent Pseudomonas aeruginosa biofilm formation was measured in standard microtitre plate assays, where it had no significant effect on either biofilm formation or development. Taken together the data suggests that GS5 treatment of surfaces may be a useful means to reducing bacterial contamination in the context of infection control practices.

A robust sebum, oil, and particulate pollution model for assessing cleansing efficacy of human skin.

With increasing concerns over the rise of atmospheric particulate pollution globally and its impact on systemic health and skin ageing, we have developed a pollution model to mimic particulate matter trapped in sebum and oils creating a robust (difficult to remove) surrogate for dirty, polluted skin. OBJECTIVE: To evaluate the cleansing efficacy/protective effect of a sonic brush vs. manual cleansing against particulate pollution (trapped in grease/oil typical of human sebum). METHODS: The pollution model (Sebollution; sebum pollution model; SPM) consists of atmospheric particulate matter/pollution combined with grease/oils typical of human sebum. Twenty subjects between the ages of 18-65 were enrolled in a single-centre, cleansing study comparisons between the sonic cleansing brush (normal speed) compared to manual cleansing. Equal amount of SPM was applied to the centre of each cheek (left and right). Method of cleansing (sonic vs. manual) was randomized to the side of the face (left or right) for each subject. Each side was cleansed for five-seconds using the sonic cleansing device with sensitive brush head or manually, using equal amounts of water and a gel cleanser. Photographs (VISIA-CR, Canfield Imaging, NJ, USA) were taken at baseline (before application of the SPM), after application of SPM (pre-cleansing), and following cleansing. Image analysis (ImageJ, NIH, Bethesda, MD, USA) was used to quantify colour intensity (amount of particulate pollutants on the skin) using a scale of 0 to 255 (0 = all black pixels; 255 = all white pixels). Differences between the baseline and post-cleansing values (pixels) are reported as the amount of SPM remaining following each method of cleansing. RESULTS: Using a robust cleansing protocol to assess removal of pollutants (SPM; atmospheric particulate matter trapped in grease/oil), the sonic brush removed significantly more SPM than manual cleansing (P < 0.001). While extreme in colour, this pollution method easily allows assessment of efficacy through image analysis.

Detection of Salmonella enterica Serovar Montevideo and Newport in Free-ranging Sea Turtles and Beach Sand in the Caribbean and Persistence in Sand and Seawater Microcosms.

Salmonellae are Gram-negative zoonotic bacteria that are frequently part of the normal reptilian gastrointestinal flora. The main objective of this project was to estimate the prevalence of non-typhoidal Salmonella enterica in the nesting and foraging populations of sea turtles on St. Kitts and in sand from known nesting beaches. Results suggest a higher prevalence of Salmonella in nesting leatherback sea turtles compared with foraging green and hawksbill sea turtles. Salmonella was cultured from 2/9 and identified by molecular diagnostic methods in 3/9 leatherback sea turtle samples. Salmonella DNA was detected in one hawksbill turtle, but viable isolates were not recovered from any hawksbill sea turtles. No Salmonella was detected in green sea turtles. In samples collected from nesting beaches, Salmonella was only recovered from a single dry sand sample. All recovered isolates were positive for the wzx gene, consistent with the O:7 serogroup. Further serotyping characterized serovars Montevideo and Newport present in cloacal and sand samples. Repetitive-element palindromic PCR (rep-PCR) fingerprint analysis and pulsed-field gel electrophoresis of the 2014 isolates from turtles and sand as well as archived Salmonella isolates recovered from leatherback sea turtles in 2012 and 2013, identified two distinct genotypes and four different pulsotypes, respectively. The genotyping and serotyping were directly correlated. To determine the persistence of representative strains of each serotype/genotype in these environments, laboratory-controlled microcosm studies were performed in water and sand (dry and wet) incubated at 25 or 35°C. Isolates persisted for at least 32 days in most microcosms, although there were significant decreases in culturable bacteria in several microcosms, with the greatest reduction in dry sand incubated at 35°C. This information provides a better understanding of the epizootiology of Salmonella in free-ranging marine reptiles and the potential public health risks associated with human interactions with these animals in the Caribbean.

A continent-wide analysis of the shade requirements of red and western grey kangaroos.

Foraging time may be constrained by a suite of phenomena including weather, which can restrict a species' activity and energy intake. This is recognized as pivotal for many species whose distributions are known to correlate with climate, including kangaroos, although such impacts are rarely quantified. We explore how differences in shade seeking, a thermoregulatory behavior, of 2 closely-related kangaroo species, Macropus rufus (red kangaroos) and M. fuliginosus (western grey kangaroos), might reflect differences in their distributions across Australia. We observed foraging and shade-seeking behavior in the field and, together with local weather observations, calculated threshold radiant temperatures (based on solar and infrared radiant heat loads) over which the kangaroos retreated to shade. We apply these calculated tolerance thresholds to hourly microclimatic estimates derived from daily-gridded weather data to predict activity constraints across the Australian continent over a 10-year period. M. fuliginosus spent more time than M. rufus in the shade (7.6 ± 0.7 h versus 6.4 ± 0.9 h) and more time foraging (11.8 ± 0.5 h vs. 10.0 ± 0.6 h), although total time resting was equivalent (∼8.2 h). M. rufus tolerated 19°C higher radiant temperatures than M. fuliginosus (89°C versus 70°C radiant temperature). Across Australia, we predicted M. fuliginosus to be more restricted to shade than M. rufus, with higher absolute shade requirements farther north. These results corroborate previous findings that M. rufus is more adept at dealing with heat than M. fuliginosus and indicate that M. rufus is less dependent on shade on a continental scale.

Dynamics of piscine francisellosis differs amongst tilapia species (Oreochromis spp.) in a controlled challenge with Francisella noatunensis subsp. orientalis.

A 25-week immersion challenge was conducted exposing Oreochromis mossambicus, Oreochromis aureus and Oreochromis urolepis hornorum to Francisella noatunensis subsp. orientalis (Fno). Two populations were compared for each fish species; 'resident fish' were defined as fish maintained in tanks since week 0 of challenge, whereas 'naïve fish' were defined as fish added to tanks once temperature in water reached <26 °C at 21 weeks post-challenge. Fno genome equivalents (GEs) in water were similar in all treatments 1 h post-challenge; however, significantly lower Fno GEs were detected 2 weeks post-challenge in all tanks, and the only treatment with detectable Fno GE after 4 weeks of challenge were the O. mossambicus tanks. Twenty-one weeks post-challenge, naïve fish were stocked with 'resident' cohorts. Over a 4-week period, mortalities occurred consistently only in O. mossambicus naïve cohorts. Overall presence of granulomas in spleen of survivors was similar (>55%) in all resident populations; however, in naïve populations, only O. mossambicus presented granulomas. Similarly, only O. mossambicus presented viable Fno in the spleen of survivors, and Fno GEs were only detected in O. mossambicus, and in resident O. aureus. In conclusion, the results of this study suggest different susceptibility of tilapia species to piscine francisellosis.

Infinite product expansion of the Fokker-Planck equation with steady-state solution.

We present an analytical technique for solving Fokker-Planck equations that have a steady-state solution by representing the solution as an infinite product rather than, as usual, an infinite sum. This method has many advantages: automatically ensuring positivity of the resulting approximation, and by design exactly matching both the short- and long-term behaviour. The efficacy of the technique is demonstrated via comparisons with computations of typical examples.

A pilot study examining the effects of consuming a high-protein vs normal-protein breakfast on free-living glycemic control in overweight/obese 'breakfast skipping' adolescents.

To examine whether the daily consumption of normal-protein (NP) vs higher-protein (HP) breakfasts improve free-living glycemic control in overweight/obese, 'breakfast skipping' adolescents. Twenty-eight healthy, but overweight, teens (age: 19±1 year; BMI: 29.9±0.8 kg m(-2)) completed a 12-week randomized parallel-arm study in which the adolescents consumed either a 350 kcal NP breakfast (13 g protein) or HP breakfast (35 g protein). Pre- and post-study 24-h blood glucose measures were assessed using continuous glucose monitoring. Although no main effects of time or group were detected, time by group interactions were observed. Post hoc pairwise comparisons assessing the post-pre changes revealed that the daily consumption of the HP breakfasts tended to reduce the 24-h glucose variability (s.d.) vs NP (-0.17±0.09 vs +0.09±0.10 s.d.; P=0.06) and tended to reduce the time spent above the high glucose limit (-292±118 vs -24±80 min; P=0.09). The consumption of the HP breakfasts also reduced the 24-h maximal (peak) glucose response (-0.94±0.36 vs +0.30±0.18 mmol l(-1); P<0.01) and reduced postprandial glucose fluctuations (-0.88±0.44 vs +0.49±0.34 mmol l(-1); P<0.03) vs NP. These data suggest that the daily addition of a HP breakfast, containing 35 g of high-quality protein, has better efficacy at improving free-living glycemic control compared with a NP breakfast in overweight/obese, but otherwise healthy, 'breakfast skipping' adolescents.

Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin.

The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and CMAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No-Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated.

Tackling the problem of blood culture contamination in the intensive care unit using an educational intervention.

Blood culture contamination (BCC) has been associated with unnecessary antibiotic use, additional laboratory tests and increased length of hospital stay thus incurring significant extra hospital costs. We set out to assess the impact of a staff educational intervention programme on decreasing intensive care unit (ICU) BCC rates to <3% (American Society for Microbiology standard). BCC rates during the pre-intervention period (January 2006-May 2011) were compared with the intervention period (June 2011-December 2012) using run chart and regression analysis. Monthly ICU BCC rates during the intervention period were reduced to a mean of 3.7%, compared to 9.5% during the baseline period (P < 0.001) with an estimated potential annual cost savings of about £250,100. The approach used was simple in design, flexible in delivery and efficient in outcomes, and may encourage its translation into clinical practice in different healthcare settings.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance.

HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.

The persistence of HIV-infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone, and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV-infected cells.

Prospective development and validation of a model to predict heart failure hospitalisation.

OBJECTIVE: Acute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking. METHODS: A prospective cohort study (n=628) of patients with stable chronic heart failure (CHF) secondary to left ventricular systolic dysfunction was used to derive an AHFS prediction model which was then assessed in a prospectively recruited validation cohort (n=462). RESULTS: Within the derivation cohort, 44 (7%) patients were hospitalised as a result of AHFS during 1 year of follow-up. Predictors of AHFS hospitalisation included furosemide equivalent dose, the presence of type 2 diabetes mellitus, AHFS hospitalisation within the previous year and pulmonary congestion on chest radiograph, all assessed at baseline. A multivariable model containing these four variables exhibited good calibration (Hosmer-Lemeshow p=0.38) and discrimination (C-statistic 0.77; 95% CI 0.71 to 0.84). Using a 2.5% risk cut-off for predicted AHFS, the model defined 38.5% of patients as low risk, with negative predictive value of 99.1%; this low risk cohort exhibited <1% excess all-cause mortality per annum when compared with contemporaneous actuarial data. Within the validation cohort, an identically applied model derived comparable performance parameters (C-statistic 0.81 (95% CI 0.74 to 0.87), Hosmer-Lemeshow p=0.15, negative predictive value 100%). CONCLUSIONS: A prospectively derived and validated model using simply obtained clinical data can identify patients with CHF at low risk of hospitalisation due to AHFS in the year following assessment. This may guide the design of future strategies allocating resources to the management of CHF.