Tangled Banks, Braided Rivers and Complex Hierarchies: Beyond Microevolution and Macroevolution.

Ever since the Modern Synthesis, a debate about the relationship between microevolution and macroevolution has persisted - specifically, whether they are equivalent, distinct, or explain one another. How one answers this has become shorthand for a much broader set of theoretical debates in evolutionary biology. Here, we examine microevolution and macroevolution in the context of the vast proliferation of data, knowledge, and theory since the advent of the Modern Synthesis. We suggest that traditional views on microevolution and macroevolution are too binary and reductive. For example, patterns and processes are not confined to micro- and macro- domains; they are interconnected at various temporal and spatial scales and across hierarchical entities. Further, biological entities have variably fuzzy boundaries, and evolutionary processes that influence macroevolution occur at micro- and macro- levels. In addition, these conceptual advances in phylodynamics have yet to be fully integrated with contemporary macroevolutionary approaches. Finally, holding microevolution and macroevolution as distinct domains thwarts synthesis and collaboration on important research questions. We propose that the focal entities and processes considered by evolutionary studies be contextualized within the newfound complexity of the multidimensional, multi-modal, multi-level phylogenetic system.

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.

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

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.

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.

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.

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.

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.

Molecular and functional characterization of vacuolar-ATPase from the American dog tick Dermacentor variabilis.

Vacuolar (V)-ATPase is a proton-translocating enzyme that acidifies cellular compartments for various functions such as receptor-mediated endocytosis, intracellular trafficking and protein degradation. Previous studies in Dermacentor variabilis chronically infected with Rickettsia montanensis have identified V-ATPase as one of the tick-derived molecules transcribed in response to rickettsial infection. To examine the role of the tick V-ATPase in tick-Rickettsia interactions, a full-length 2887-bp cDNA (2532-bp open reading frame) clone corresponding to the transcript of the V0 domain subunit a of D. variabilis V-ATPase (DvVATPaseV0a) gene encoding an 843 amino acid protein with an estimated molecular weight of ~96 kDa was isolated from D. variabilis. Amino acid sequence analysis of DvVATPaseV0a showed the highest similarity to VATPaseV0a from Ixodes scapularis. A potential N-glycosylation site and eight putative transmembrane segments were identified in the sequence. Western blot analysis of tick tissues probed with polyclonal antibody raised against recombinant DvVATPaseV0a revealed the expression of V-ATPase in the tick ovary. Transcriptional profiles of DvVATPaseV0a demonstrated a greater mRNA expression in the tick ovary, compared with the midgut and salivary glands; however, the mRNA level in each of these tick tissues remained unchanged after infection with R. montanensis for 1 h. V-ATPase inhibition bioassays resulted in a significant decrease in the ability of R. montanensis to invade tick cells in vitro, suggesting a role of V-ATPase in rickettsial infection of tick cells. Characterization of tick-derived molecules involved in rickettsial infection is essential for a thorough understanding of rickettsial transmission within tick populations and the ecology of tick-borne rickettsial diseases.

Hospital antibiotic use and its relationship to age-adjusted comorbidity and alcohol-based hand rub consumption.

The objective of this study was to evaluate the effect of age-adjusted comorbidity and alcohol-based hand rub on monthly hospital antibiotic usage, retrospectively. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate the monthly use of all antibiotics grouped together with age-adjusted comorbidity and alcohol-based hand rub over a 5-year period (April 2005-March 2010). The results showed that monthly antibiotic use was positively related to the age-adjusted comorbidity index (concomitant effect, coefficient 1·103, P = 0·0002), and negatively related to the use of alcohol-based hand rub (2-month delay, coefficient -0·069, P = 0·0533). Alcohol-based hand rub is considered a modifiable factor and as such can be identified as a target for quality improvement programmes. Time-series analysis may provide a suitable methodology for identifying possible predictive variables that explain antibiotic use in healthcare settings. Future research should examine the relationship between infection control practices and antibiotic use, identify other infection control predictive factors for hospital antibiotic use, and evaluate the impact of enhancing different infection control practices on antibiotic use in a healthcare setting.

Impact of an enhanced antibiotic stewardship on reducing methicillin-resistant Staphylococcus aureus in primary and secondary healthcare settings.

The objective of this study was to evaluate the impact of restricting high-risk antibiotics on methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in a hospital setting. A secondary objective was to assess the impact of reducing fluoroquinolone use in the primary-care setting on MRSA incidence in the community. This was an interventional, retrospective, ecological investigation in both hospital and community (January 2006 to June 2010). Segmented regression analysis of interrupted time-series was employed to evaluate the intervention. The restriction of high-risk antibiotics was associated with a significant change in hospital MRSA incidence trend (coefficient=-0·00561, P=0·0057). Analysis showed that the intervention relating to reducing fluoroquinolone use in the community was associated with a significant trend change in MRSA incidence in community (coefficient=-0·00004, P=0·0299). The reduction in high-risk antibiotic use and fluoroquinolone use contributed to both a reduction in incidence rates of MRSA in hospital and community (primary-care) settings.

Fruit and vegetables on prescription: a brief intervention in primary care.

BACKGROUND: Increasing fruit and vegetable consumption is a goal for the U.K. Therefore, the effectiveness of a fruit and vegetable voucher scheme coupled with key 'five-a-day' consumption messages as a brief intervention in primary care consultations was assessed in the present study. METHODS: One thousand one hundred and eighty-eight vouchers as a prescription for fruits and vegetables were routinely distributed to patients attending a primary healthcare centre in a deprived area, and 124 volunteer patients routinely attending the centre were included. Telephone-based questionnaires were used to examine changes in consumption over the short and medium term. Other key aspects assessed in the evaluation related to fruit and vegetable purchasing behaviour, knowledge relating to what constitutes a portion size, the relationship between food and health, and barriers to consumption. RESULTS: Although 76.2% of participants used the prescription vouchers when purchasing fruits and vegetables, a significant change in the consumption or purchasing behaviour was not observed (P > 0.05). Participants' level of knowledge relating to the number of portions recommended and the portion size of different fruits and vegetables showed a moderate increase from baseline over the short and medium term. The primary barriers to fruit and vegetable consumption were reported as 'the quality of fresh fruits and vegetables' and 'the money available to spend on food'. CONCLUSIONS: The use of 'the fruit and vegetable on prescription' scheme was an effective method of engaging participants in improving awareness of key diet-related health messages. However, further intervention is required to produce a significant impact on the actual behaviour change.

Induction of defence response in peanut elicited by Bacillus sp. CHEP5: A biological strategy for control of smut disease caused by Thecaphora frezzii in the field.

Peanut is susceptible to many diseases; among them, peanut smut disease caused by Thecaphora frezzii is the most damaging, causing yield losses of 30%. Fungicide treatment is not effective to control this disease. In this scenario, biological control would be an alternative to diminish the disease. Systemic resistance induced by a biotic agent is known to be effective against a broad spectrum of pathogens. In this study we evaluated the effect of different inoculation strategies of Bacillus sp. CHEP5, a peanut native strain, on peanut smut incidence and severity in field experiments. Peroxidase activity and accumulation of phenolic compounds were measured as changes associated with induced defensive traits. After three consecutive field trials, we found that Bacillus sp. CHEP5 inoculation protects peanut from T. frezzii because incidence and severity were reduced in two field trials. Furthermore, bacterial inoculation in the furrow followed by foliar application around the date of peg development would be the best strategy to control the disease. In addition, a correlation was found between increase in plant phenolic content and decrease in smut disease parameters. Thereafter, we concluded that Bacillus sp. CHEP5 may reduce smut as a result of plant defence response induction.

Ocular TB in Western Australia.

This was a retrospective chart review in Western Australia, Australia.To describe the diagnosis, management, and treatment outcomes of ocular TB in Western Australia (WA).This was a retrospective review of ocular TB cases in WA from 2007 to 2018 with a minimum 2-year follow-up upon completion of anti-TB therapy (ATT).A total of 44 patients were referred to WA TB clinic. Ten were excluded from the analysis of treatment response; 34 met the inclusion criteria, of whom 97.1% were born overseas. No patients had symptomatic extraocular TB. Chest X-ray showed prior pulmonary TB in 11.7% of patients (n = 4). All patients were treated with three or four ATT drugs. The most common ocular TB manifestation was retinal vasculitis (23.5%). Full resolution of ocular inflammation following ATT occurred in 66.7% (n = 22), and reduced ocular inflammation requiring only topical steroid treatment was seen in 21.2% (n = 7). Treatment failure occurred in 12.1% (n = 4). Side effects were reported in 45.6% of patients, with gastrointestinal symptoms most common (27.2%).Our study is the first Australian study examining the management of ocular TB. Our study highlights the challenges in diagnosing TB ocular disease in a low-endemicity setting and the importance of the collaboration between uveitis and TB subspecialists..

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.

Molecular characterization and tissue-specific gene expression of Dermacentor variabilis α-catenin in response to rickettsial infection.

Alpha catenin is a cytoskeleton protein that acts as a regulator of actin rearrangement by forming an E-cadherin adhesion complex. In Dermacentor variabilis, a putative α-catenin (Dvα-catenin) was previously identified as differentially regulated in ovaries of ticks chronically infected with Rickettsia montanensis. To begin characterizing the role(s) of Dvα-catenin during rickettsial infection, the full-length Dvα-catenin cDNA was cloned and analysed. Comparative sequence analysis demonstrates a 3069-bp cDNA with a 2718-bp open reading frame with a sequence similar to Ixodes scapularisα-catenin. A portion of Dvα-catenin is homologous to the vinculin-conserved domain containing a putative actin-binding region and ß-catenin-binding and -dimerization regions. Quantitative reverse-transcription PCR analysis demonstrated that Dvα-catenin is predominantly expressed in tick ovaries and is responsive to tick feeding. The tissue-specific gene expression analysis of ticks exposed to Rickettsia demonstrates that Dvα-catenin expression was significantly downregulated 12 h after exposure to R. montanensis, but not in Rickettsia amblyommii-exposed ovaries, compared with Rickettsia-unexposed ticks. Studying tick-derived molecules associated with rickettsial infection will provide a better understanding of the transmission dynamics of tick-borne rickettsial diseases.

Physiological implications of genomic state in parthenogenetic lizards of reciprocal hybrid origin.

Parthenogenesis often evolves in association with hybridization, but the associated ecological consequences are poorly understood. The Australian gecko Heteronotia binoei is unusual because triploid parthenogenesis evolved through reciprocal crosses between two sexual lineages, resulting in four possible cytonuclear genotypes. In this species complex, we compared the performance of these parthenogenetic genotypes with their sexual progenitors for a suite of physiological traits (metabolic rate, thermal tolerance, locomotor performance, and in vitro activity and gene sequence divergence of a cytonuclear metabolic pathway, cytochrome C oxidase). Mass-specific metabolic rate scaled differently with body mass for parthenogens and sexuals, while heat tolerance provided the only evidence for cytonuclear incompatibility in hybrid parthenogens. The most prominent phenotypic effects were attributable to nuclear genome dosage. Overall, our results suggest that the hybrid/polyploidy origin of parthenogenetic H. binoei has had surprisingly few negative fitness consequences and may have produced a broader overall niche for the species.

A point prevalence survey of antibiotic use in four acute-care teaching hospitals utilizing the European Surveillance of Antimicrobial Consumption (ESAC) audit tool.

The objective of this research was to assess current patterns of hospital antibiotic prescribing in Northern Ireland and to determine targets for improving the quality of antibiotic prescribing. A point prevalence survey was conducted in four acute teaching hospitals. The most commonly used antibiotics were combinations of penicillins including ß-lactamase inhibitors (33·6%), metronidazole (9·1%), and macrolides (8·1%). The indication for treatment was recorded in 84·3% of the prescribing episodes. A small fraction (3·9%) of the surgical prophylactic antibiotic prescriptions was for >24 h. The results showed that overall 52·4% of the prescribed antibiotics were in compliance with the hospital antibiotic guidelines. The findings identified the following indicators as targets for quality improvement: indication recorded in patient notes, the duration of surgical prophylaxis and compliance with hospital antibiotic guidelines. The results strongly suggest that antibiotic use could be improved by taking steps to address the identified targets for quality improvement.

Diabetes mellitus and the heart.

Diabetes mellitus is a risk factor for the development of coronary artery disease and chronic heart failure. When carefully screened for, diabetes or prediabetic disorders, are present in the majority of patients with clinically manifest ischaemic heart disease, and confer a major adverse impact upon morbidity and mortality. Important therapeutic modifications are required in the management of coronary artery disease and chronic heart failure associated with diabetes, and vice versa. However, despite optimal management, aided by recent landmark trials solely recruiting patients with diabetes, outcomes for patients with diabetes and heart disease remain poor. This review outlines the epidemiology, pathogenesis and management of diabetic heart disease, along with highlighting the many gaps in the evidence-base and suggesting future research priorities.

Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.