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Local adaptation is common in plants, yet characterization of its underlying genetic basis is rare in herbaceous perennials. Moreover, while many plant species exhibit intraspecific chemical defence polymorphisms, their importance for local adaptation remains poorly understood. We examined the genetic architecture of local adaptation in a perennial, obligately-outcrossing herbaceous legume, white clover (Trifolium repens). This widespread species displays a well-studied chemical defence polymorphism for cyanogenesis (HCN release following tissue damage) and has evolved climate-associated cyanogenesis clines throughout its range. Two biparental F2 mapping populations, derived from three parents collected in environments spanning the U.S. latitudinal species range (Duluth, MN, St. Louis, MO and Gainesville, FL), were grown in triplicate for two years in reciprocal common garden experiments in the parental environments (6,012 total plants). Vegetative growth and reproductive fitness traits displayed trade-offs across reciprocal environments, indicating local adaptation. Genetic mapping of fitness traits revealed a genetic architecture characterized by allelic trade-offs between environments, with 100% and 80% of fitness QTL in the two mapping populations showing significant QTL×E interactions, consistent with antagonistic pleiotropy. Across the genome there were three hotspots of QTL colocalization. Unexpectedly, we found little evidence that the cyanogenesis polymorphism contributes to local adaptation. Instead, divergent life history strategies in reciprocal environments were major fitness determinants: selection favoured early investment in flowering at the cost of multiyear survival in the southernmost site versus delayed flowering and multiyear persistence in the northern environments. Our findings demonstrate that multilocus genetic trade-offs contribute to contrasting life history characteristics that allow for local adaptation in this outcrossing herbaceous perennial.

The Next Generation Transit Survey (NGTS) is a photometric survey for transiting exoplanets, consisting of 12 identical 0.2‐m telescopes. We report a measurement of the transit of HD 106315 c using a novel observing mode in which multiple NGTS telescopes observed the same target, with the aim of increasing the signal‐to‐noise ratio. Combining the data allows the robust detection of the transit, which has a depth less than 0.1%, rivaling the performance of much larger telescopes. We demonstrate the capability of NGTS to contribute to the follow‐up of K2 and Transiting Exoplanet Survey Satellite discoveries using this observing mode. In particular, NGTS is well‐suited to the measurement of shallow transits of bright targets. This is particularly important to improve orbital ephemerides of relatively long‐period planets, where only a small number of transits are observed from space.

We present ground- and space-based photometric observations of TOI-270 (L231-32), a system of three transiting planets consisting of one super-Earth and two sub-Neptunes discovered by TESS around a bright (K-mag = 8.25) M3V dwarf. The planets orbit near low-order mean-motion resonances (5:3 and 2:1) and are thus expected to exhibit large transit timing variations (TTVs). Following an extensive observing campaign using eight different observatories between 2018 and 2020, we now report a clear detection of TTVs for planets c and d, with amplitudes of ∼10 min and a super-period of ∼3 yr, as well as significantly refined estimates of the radii and mean orbital periods of all three planets. Dynamical modelling of the TTVs alone puts strong constraints on the mass ratio of planets c and d and on their eccentricities. When incorporating recently published constraints from radial velocity observations, we obtain masses of $M_{\mathrm{b}}=1.48\pm 0.18\, M_\oplus$, $M_{\mathrm{c}}=6.20\pm 0.31\, M_\oplus$, and $M_{\mathrm{d}}=4.20\pm 0.16\, M_\oplus$ for planets b, c, and d, respectively. We also detect small but significant eccentricities for all three planets : eb = 0.0167 ± 0.0084, ec = 0.0044 ± 0.0006, and ed = 0.0066 ± 0.0020. Our findings imply an Earth-like rocky composition for the inner planet, and Earth-like cores with an additional He/H2O atmosphere for the outer two. TOI-270 is now one of the best constrained systems of small transiting planets, and it remains an excellent target for atmospheric characterization.

BACKGROUND The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use. OBJECTIVE The primary objective is to assess the current legislation on sunbed use among European countries. METHODS We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network. RESULTS We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown. CONCLUSIONS Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis.

Background Understanding the importance of the barrier function of the skin of preterm and term neonates is crucial in effective neonatal skin and diaper care. This literature search aimed to review the development of different practices in neonatal care to maintain skin barrier function, in turn preventing diaper dermatitis. Methods We performed two quantitative literature searches of English language studies: an initial literature search of studies published in the last 5 years was conducted using Cinahl, Medline, Embase, British Nursing Index, and DelphiS, followed by a second search of publications from 1990 to 2017 using the National Institute of Clinical Excellence Health Databases Advanced Search using key words, synonyms, and Boolean phrasing. Titles and abstracts were reviewed for relevance. Results One hundred ten studies were analyzed for the purpose of this review; however, data are of variable quality. Guidance can be drawn from the existing literature relating to best practice options for diaper area cleansing methods, diaper type selection, and use of barrier creams. More research is required into the benefit or otherwise of diaper-free time. Conclusions Super-absorbent diapers reduce moisture at skin level and reduce diaper dermatitis. Barrier creams carry benefit both in prevention and cure but do not provide a substitute for frequent diaper changes. The literature does not demonstrate superiority of one cleansing method over another, but neither the use of wipes nor water increases diaper dermatitis prevalence. Further studies are required to explore the potential benefit of diaper-free time, taking due consideration of the practicalities, particularly for vulnerable neonates within the Intensive Care setting.

This literature review explores the association between body mass index and self-esteem in nurses, alongside their attitudes towards patients who have obesity. These variables have either previously been linked to weight bias, or with prejudice more generally, but findings in this context are inconclusive. Searches were conducted through Psychology Cross Search, PubMed, Web of Science, Proquest Allied Health Professionals and Google Scholar. Ten studies met the inclusion criteria and were tabulated and critiqued using appropriate appraisal tools. The literature covered a time span of over 30 years with the type and quality of study methodologies varying. Research was rarely underpinned by theory. As such, no consensus was reached in drawing together the findings but the direction of future research needed to address these issues is discussed. Further research should focus on developing the literature using an appropriate theoretical underpinning in order to better understand the research that has begun further afield.

BACKGROUND: This study aims to characterize the trends in disease presentation for robot-assisted radical prostatectomy (RARP) over a 12-year period in Melbourne, Australia. METHODS: All patients undergoing an RARP between 2004 and October 2016 while under the care of six high-volume surgeons were included in this study. Data were collected prospectively regarding patient demographics and clinical details of their cancer. RESULTS: Over the 12-year time span of the study, 3075 men underwent an RARP with a median age of 63.01 years. Temporal analysis demonstrated that the median age of patients undergoing prostatectomy advanced with time with the median age in 2016 being 65.51 years compared with 61.0 years in 2004 (P < 0.001). There was also a significant trend to increased D'Amico risk groups over time with the percentage procedures for high-risk patients increasing from 12.6% to 28.10% from 2004 to 2016 (P < 0.001). Upgrade rates between biopsy and pathological Gleason grade scoring significantly trended down over the period of the study (P < 0.001). There was also a shift to increased pathological stage over the 12 years with 22.1% of men having T3 disease in 2004 compared with 49.8% in 2016. CONCLUSION: Our analysis demonstrates increasing treatment of older men with higher risk tumours, consistent with international trends. While this largely reflects a shift in case selection, further work is needed to assess whether the stage shift may relate partially to a decline in screening and increased presentation of higher risk disease.

CLV3/ESR (CLE) proteins are important signaling peptides in plants. The short CLE peptide (12-13 amino acids) is cleaved from a larger pre-propeptide and functions as an extracellular ligand. The CLE family is large and has resisted attempts at classification because the CLE domain is too short for reliable phylogenetic analysis and the pre-propeptide is too variable. We used a model-based search for CLE domains from 57 plant genomes and used the entire pre-propeptide for comprehensive clustering analysis. In total, 1628 CLE genes were identified in land plants, with none recognizable from green algae. These CLEs form 12 groups within which CLE domains are largely conserved and pre-propeptides can be aligned. Most clusters contain sequences from monocots, eudicots and Amborella trichopoda, with sequences from Picea abies, Selaginella moellendorffii and Physcomitrella patens scattered in some clusters. We easily identified previously known clusters involved in vascular differentiation and nodulation. In addition, we found a number of discrete groups whose function remains poorly characterized. Available data indicate that CLE proteins within a cluster are likely to share function, whereas those from different clusters play at least partially different roles. Our analysis provides a foundation for future evolutionary and functional studies.

Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further studies are needed to better delineate the interactions that can occur in normal and diseased states. Therapeutic measures might be forthcoming especially for skin diseases such as eczema, which are regarded as being characterized by 'skin dryness'. Further research examining the interaction between different environmental exposures thought to impact the skin, and indeed the interplay between genetic, environmental and immunological influences, are required.

Background Treatment monitoring is subjective and disease relapse is common in cats with histoplasmosis. The Histoplasma antigen enzyme immunoassay (EIA) is a noninvasive test used for determining disease remission and detecting disease relapse in humans with histoplasmosis. The utility of the antigen EIA for these purposes in cats remains unknown. Hypothesis/Objectives Those Histoplasma antigen concentrations in urine and serum would decline with antifungal treatment and that antigen elimination would be an indicator of clinical remission in cats with histoplasmosis treated with antifungal treatment. Animals Fifteen client-owned cats with histoplasmosis. Methods Masked observational study. Cats were monitored monthly during antifungal treatment. Time of clinical remission and serum and urine antigen elimination were determined for each cat. Results Twelve of 15 cats achieved clinical remission. At the time of diagnosis, antigen was detectable in urine in 14/15 (93%) cats and in serum in 11/15 (73%) cats. Both serum (P < .0005) and urine (P < .0001) antigen concentrations significantly decreased over time with effective treatment. Antigen elimination was sensitive [urine, 90.0% (95% CI 72.3–97.4%); serum, 90.4% (68.2–98.3%)] but less specific [urine, 64.6% (51.7–75.8%); serum, 52.1% (37.4–66.5%)] for disease remission. Urine antigen was positive in both cats and serum antigen was positive in 1 cat at the time of disease relapse. Conclusions and Clinical Importance Measurement of Histoplasma antigen in urine and serum might be useful tests for determining disease remission and relapse in cats with histoplasmosis. Further research is needed to investigate the importance of low-level antigenemia and antigenuria.

Objectives To compare patterns of care and peri-operative outcomes of robot-assisted radical prostatectomy (RARP) with other surgical approaches, and to create an economic model to assess the viability of RARP in the public case-mix funding system. Patients and Methods We retrospectively reviewed all radical prostatectomies (RPs) performed for localized prostate cancer in Victoria, Australia, from the Victorian Admitted Episode Dataset, a large administrative database that records all hospital inpatient episodes in Victoria. The first database, covering the period from July 2010 to April 2013 (n = 5 130), was used to compare length of hospital stay (LOS) and blood transfusion rates between surgical approaches. This was subsequently integrated into an economic model. A second database (n = 5 581) was extracted to cover the period between July 2010 and June 2013, three full financial years, to depict patterns of care and make future predictions for the 2014–2015 financial year, and to perform a hospital volume analysis. We then created an economic model to evaluate the incremental cost of RARP vs open RP (ORP) and laparoscopic RP (LRP), incorporating the cost-offset from differences in LOS and blood transfusion rate. The economic model constructs estimates of the diagnosis-related group (DRG) costs of ORP and LRP, adds the gross cost of the surgical robot (capital, consumables, maintenance and repairs), and manipulates these DRG costs to obtain a DRG cost per day, which can be used to estimate the cost-offset associated with RARP in comparison with ORP and LRP. Economic modelling was performed around a base-case scenario, assuming a 7-year robot lifespan and 124 RARPs performed per financial year. One- and two-way sensitivity analyses were performed for the four-arm da Vinci SHD, Si and Si dual surgical systems (Intuitive Surgical Ltd, Sunnyvale, CA, USA). Results We identified 5 581 patients who underwent RP in 20 hospitals in Victoria with an open, laparoscopic or robot-assisted surgical approach in the public and private sector. The majority of RPs (4 233, 75.8%), in Victoria were performed in the private sector, with an overall 11.5% decrease in the total number of RPs performed over the 3-year study period. In the most recent financial year, 820 (47%), 765 (44%) and 173 patients (10%) underwent RARP, ORP and LRP, respectively. In the same timeframe, RARP accounted for 26 and 53% of all RPs in the public and private sector, respectively. Public hospitals in Victoria perform a median number of 14 RPs per year and 40% of hospitals perform

Objective To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation. Patients and Methods Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital. Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features. The Australian Standard Geographical Classification-Remoteness Area (ASGC-RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3. Statistical significance was specified as P < 0.05 on Pearson's chi-square tests. Results Patients in each ASGC-RA group did not differ significantly in age, sex or mode of presentation. Pathological T stage on presentation increased with increasing ASGC-RA and thus distance from tertiary centres (P = 0.004). The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003). When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC-RA (P < 0.001), symptomatic presentation (P < 0.001), N stage (P < 0.001), M stage (P < 0.001) and Fuhrman grade (P < 0.001). Conclusions Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer. Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.

Key Clinical Message We report a 53-year-old man diagnosed with Richter syndrome. He was heavily pretreated and was refractory to prior therapy. He received rituximab and ibrutinib, and achieved a significant response after 1 month of therapy. Our case illustrates the importance of investigation of rituximab and ibrutinib in Richter’s syndrome.

The flocculation process is commonly used to separate suspended solids from water. The microalgae strain, Picochlorum oklahomensis (PO), was investigated for its flocculation characteristics. Efficiencies of biopolymer addition, pH adjustment and electroflocculation for biomass recovery from the culture medium were examined. Flocculation efficiency of PO increased sharply above pH 11 and reached 97 % at pH 13. Chitosan was more effective in flocculating PO cells than sodium alginate and cationic starch. A generalized linear mixed model using a beta distribution for response was utilized for optimization of the chitosan flocculation process variables. Biomass: chitosan ratio, pH and settling time (ST) were the independent variables. There were significant 3-way interactions among the variables. The highest PO flocculation efficiency, 98.4 %, was obtained at biomass: chitosan ratio of 2.78, pH 9 and ST of 12 h. The electroflocculation efficiency improved with increasing current, operation time (OT) and ST. The highest electroflocculation efficiency, 99.74 %, was obtained under the following conditions; 0.8 A (ampere) and 15 min and 12 h, OT and ST, respectively. This study demonstrated that pH adjustment, chitosan addition and electroflocculation were all technically viable methods to flocculate PO cells. However, selection of the most suitable technique and the optimum treatment conditions needs to be based not only on the application of algal biomass, but also on an economic feasibility study.

Summary 1. Patterns of landscape heterogeneity are crucial to the maintenance of biodiversity in shrublands and grasslands, yet management practices in these ecosystems typically seek to homogenize landscapes. Furthermore, there is limited understanding of how the interaction of ecological processes, such as fire and grazing, affects patterns of heterogeneity at different spatial scales. 2. We conducted research in Artemisia filifolia (Asteraceae) shrublands located in the southern Great Plains of North America to determine the effect of restoring the fire–grazing interaction on vegetation structure. Data were collected for 3 years in replicated pastures grazed by cattle Bos taurus where the fire–grazing interaction had been restored (fire and grazing = treatment pastures) and in pastures that were grazed but remained unburned (grazing only, no fire = control pastures). The effect of the fire–grazing interaction on heterogeneity (variance) of vegetation structure was assessed at scales from 12·5 m2 to 609 ha. 3. Most measurements of vegetation structure within treatment pastures differed from control pastures for 1–3 years after being burned but were thereafter similar to the values found in unburned control pastures. 4. Treatment pastures were characterized by a lower amount of total heterogeneity and a lower amount of heterogeneity through time. 5. Heterogeneity of vegetation structure tended to decrease as the scale of measurement increased in both treatment and control pastures. There was deviation from this trend, however, in the treatment pastures that exhibited much higher heterogeneity at the patch scale (mean patch size = 202 ha) of measurement, the scale at which patch fires were conducted. 6.Synthesis and applications. Vegetation structure in A. filifolia shrublands of our study was readily altered by the fire–grazing interaction but also demonstrated substantial resilience to these effects. The fire–grazing interaction also changed the total amount of heterogeneity characterizing this system, the scale at which heterogeneity in this system was expressed and the amount of heterogeneity expressed through time. Land managers seeking to impose a shifting mosaic of heterogeneity on this vegetation type can do so by restoring the fire–grazing interaction with potential conservation benefits similar to what has been achieved in other ecosystems where historic cycles of disturbance and rest have been restored.

The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

Select beef loin pairs (n = 10) were injected (10% pump) with brine containing either 4.5% sodium-based phosphates, (CON), or 1% ammonium hydroxide treatment (AHT). Both brines also contained 3.6% NaCl and 1% Rosemary Herbalox. Steaks cut from loins were high oxygen (80% O(2)/20% CO(2)) modified atmosphere packaged, stored 4 d at 4 °C in the dark to simulate transportation, and then placed in retail display for 14 d (4 °C). On day 0, 7, and 14 of retail display steak properties were measured. Purge from AHT steaks was higher than CON (P0.05). Panelists were not able to visually discriminate between AHT and CON steaks through the first 6 d of retail display. After day 6, panelists rated AHT steaks higher for muscle color, percent discoloration, and overall color. Steaks from both treatments started at day 0 retail display with similar total plate counts (P0.05). Microbial counts increased more rapidly for AHT steaks than CON steaks (P0.05). AHT and CON steaks were not different in terms of lipid oxidation through day 7 retail display. By day 14 retail display CON steaks were above the threshold for consumer perception of oxidized flavors in fresh meat. However, results also indicated the AHT and CON steaks were no longer acceptable by day 14 in terms of color, were questionable in terms of microbial load, and likely were beyond their reasonable shelf life. Based on retail display properties, results indicated 1% AHT could successfully replace 4.5% SP in a meat injection brine. Practical Application: The research in this report compares steaks that have been injected with a commercial brine formulated with SP to steaks that have been injected with a brine, where the SP in the formulation are replaced with 1% AHT. Ammonium hydroxide is an USDA-FSIS approved ingredient in brines injected into fresh meats. Successful replacement of sodium phosphate with ammonium hydroxide would allow processors to significantly reduce the sodium content of injected fresh meat.