Morphological ghosts of introgression in Darwin's finch populations.

Many species of plants, animals, and microorganisms exchange genes well after the point of evolutionary divergence at which taxonomists recognize them as species. Genomes contain signatures of past gene exchange and, in some cases, they reveal a legacy of lineages that no longer exist. But genomic data are not available for many organisms, and particularly problematic for reconstructing and interpreting evolutionary history are communities that have been depleted by extinctions. For these, morphology may substitute for genes, as exemplified by the history of Darwin's finches on the Galápagos islands of Floreana and San Cristóbal. Darwin and companions collected seven specimens of a uniquely large form of Geospiza magnirostris in 1835. The populations became extinct in the next few decades, partly due to destruction of Opuntia cactus by introduced goats, whereas Geospiza fortis has persisted to the present. We used measurements of large samples of G. fortis collected for museums in the period 1891 to 1906 to test for unusually large variances and skewed distributions of beak and body size resulting from introgression. We found strong evidence of hybridization on Floreana but not on San Cristóbal. The skew is in the direction of the absent G. magnirostris We estimate introgression influenced 6% of the frequency distribution that was eroded by selection after G. magnirostris became extinct on these islands. The genetic residuum of an extinct species in an extant one has implications for its future evolution, as well as for a conservation program of reintroductions in extinction-depleted communities.

Assessment of a goal-directed perfusion strategy through an oxygen delivery audit.

INTRODUCTION: Evidence supports the role of oxygen delivery (DO2) in ameliorating acute kidney injury (AKI). While instrumentation for continuous DO2 measurement exists, a simplified method has been reported for targeting a specific DO2 index (DO2i), commonly referred to as a goal-directed perfusion (GDP) strategy, by using a reference table and available data such as body surface area and continuous haematocrit values. This simplified approach can also be used for quality auditing via archived data. METHODS: This retrospective sequential audit was conducted to assess the impact of employing a GDP strategy within our institution by examining perfusion practices, DO2 levels and renal outcomes before and after implementation. A total of 246 patients undergoing elective primary coronary revascularisation were included: 125 patients in the pre-change group and 121 patients in the post-change group. A DO2i threshold above 280 mL/min/m2 was targeted in the post-GDP group. RESULTS: While both groups maintained a mean DO2 above the threshold, the post-GDP group exhibited a higher average DO2i (311 vs 291 mL/min/m2). The GDP strategy led to higher nadir DO2i (255 vs 225, p < .001) and was coupled with a reduction in the time below the 280 mL/min/m2 threshold (30 min vs 50 min, p < .001). The average cardiac index in the post-GDP group was higher (1.87 vs 1.65, p < .001) while also demonstrating a smaller creatinine rise of 6.8% compared to 13.5% in the control group (p = .035). There was no difference in AKI or mortality rates between the groups. CONCLUSION: The implementation of the GDP strategy demonstrated an enhancement in oxygen delivery during cardiopulmonary bypass, primarily attributable to elevated pump flow rates. A statistically significant decrease in serum creatinine levels was observed. The published reference table emerged as a simple yet effective tool in optimising our GDP strategy.

Quantifying the Impact of Motions on Human Aiming Performance: Evidence from Eye Tracking and Bio-Signals.

Working on a moving platform can significantly impede human performance. Previous studies on moving vehicles have often focused on the overall impact on general task performance, whereas our study's emphasis is on precise hand movements, exploring the interaction between body motion and the escalation of task difficulty. We recruited 28 participants to engage in reciprocal aiming tasks, following Paul Fitts's setting, under both in-motion and stationary conditions. The task index of difficulty (ID) was manipulated by varying the width of the targets and the distance between the targets. We measured participants' movement time (MT), performance errors, and monitored their eye movements using an eye-tracking device, heart rate (HR), and respiration rate (RR) during the tasks. The measured parameters were compared across two experimental conditions and three ID levels. Compared to the stationary conditions, the in-motion conditions degraded human aiming performance, resulting in significantly prolonged MT, increased errors, and longer durations of eye fixations and saccades. Furthermore, HR and RR increased under the in-motion conditions. Linear relationships between MT and ID exhibited steeper slopes under the in-motion conditions compared to the stationary conditions. This study builds a foundation for us to explore the control mechanisms of individuals working in dynamic and demanding environments, such as pilots in airplanes and paramedics in ambulances.

Is Transcatheter Aortic Valve Implantation (TAVI) Activity in Australia Consistent With International Guidelines?

BACKGROUND: Transcatheter aortic valve implantation (TAVI) did not receive regulatory approval in Australia until 2013, several years after Europe (2007) and America (2011). Consequently, the uptake of TAVI in Australia initially lagged behind international best practices. This study was undertaken to provide an update on the status of TAVI activity in Australia. METHOD: A descriptive population-level epidemiological study was performed. Annual activity data for both surgical aortic valve replacement (SAVR) and TAVI were obtained from the Australian Institute of Health and Welfare (AIHW) for the period from 1 July 2012 to 30 June 2022. Dynamic contemporaneous population data were obtained from the Australian Bureau of Statistics (ABS). Trends in absolute activity, population-adjusted activity and age cohort-adjusted activity were examined. RESULTS: Despite the impact of the COVID-19 pandemic on the Australian healthcare system, TAVI activity has continued to increase. Annual TAVI activity now exceeds annual SAVR activity (3,967 vs 3,870), albeit driven by TAVI in patients aged 85+ years. Population-adjusted TAVI activity now exceeds the reported European average (15.3 vs 14.1 per 100,000 persons). The point of equipoise for the choice between SAVR and TAVI is the 75-79 age cohort (50% vs 50%). CONCLUSIONS: Australian TAVI activity is now consistent with international best practice.

Evaluation of out-of-pocket pay genetic testing in a publicly funded healthcare system.

When genetic tests are not funded publicly, out-of-pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving >12 000 patients/year (The Hereditary Cancer Program [HCP] and Provincial Medical Genetics Program [PMGP]) between 2015-2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p < 0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI: 1.04, 1.10); while this likelihood had an immediate 87% drop when the change occurred (OR: 0.13; 95% CI: 0.06, 0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay.

Triad hybridization via a conduit species.

Introgressive hybridization can affect the evolution of populations in several important ways. It may retard or reverse divergence of species, enable the development of novel traits, enhance the potential for future evolution by elevating levels of standing variation, create new species, and alleviate inbreeding depression in small populations. Most of what is known of contemporary hybridization in nature comes from the study of pairs of species, either coexisting in the same habitat or distributed parapatrically and separated by a hybrid zone. More rarely, three species form an interbreeding complex (triad), reported in vertebrates, insects, and plants. Often, one species acts as a genetic link or conduit for the passage of genes (alleles) between two others that rarely, if ever, hybridize. Demographic and genetic consequences are unknown. Here we report results of a long-term study of interbreeding Darwin's finches on Daphne Major island, Galápagos. Geospiza fortis acted as a conduit for the passage of genes between two others that have never been observed to interbreed on Daphne: Geospiza fuliginosa, a rare immigrant, and Geospiza scandens, a resident. Microsatellite gene flow from G. fortis into G. scandens increased in frequency during 30 y of favorable ecological conditions, resulting in genetic and morphological convergence. G. fortis, G. scandens, and the derived dihybrids and trihybrids experienced approximately equal fitness. Especially relevant to young adaptive radiations, where species differ principally in ecology and behavior, these findings illustrate how new combinations of genes created by hybridization among three species can enhance the potential for evolutionary change.

Genetic and transcriptomic analyses support a switch to lytic phase in Epstein Barr virus infection as an important driver in developing Systemic Lupus Erythematosus.

To investigate the molecular mechanisms through which Epstein-Barr virus (EBV) may contribute to Systemic Lupus Erythematosus (SLE) pathogenesis, we interrogated SLE genetic risk loci for signatures of EBV infection. We first compared the gene expression profile of SLE risk genes across 459 different cell/tissue types. EBV-infected B cells (LCLs) had the strongest representation of highly expressed SLE risk genes. By determining an SLE risk allele effect on gene expression (expression quantitative trait loci, eQTL) in LCLs and 16 other immune cell types, we identified 79 SLE risk locus:gene pairs putatively interacting with EBV infection. A total of 10 SLE risk genes from this list (CD40, LYST, JAZF1, IRF5, BLK, IKZF2, IL12RB2, FAM167A, PTPRC and SLC15A) were targeted by the EBV transcription factor, EBNA2, differentially expressed between LCLs and B cells, and the majority were also associated with EBV DNA copy number, and expression level of EBV encoded genes. Our final gene network model based on these genes is suggestive of a nexus involving SLE risk loci and EBV latency III and B cell proliferation signalling pathways. Collectively, our findings provide further evidence to support the interaction between SLE risk loci and EBV infection that is in part mediated by EBNA2. This interplay may increase the tendency towards EBV lytic switching dependent on the presence of SLE risk alleles. These results support further investigation into targeting EBV as a therapeutic strategy for SLE.

Evaluating patient-reported symptoms and late adverse effects following completion of first-line chemotherapy for ovarian cancer using the MOST (Measure of Ovarian Symptoms and Treatment concerns).

OBJECTIVES: Knowledge on the course of symptoms patients with ovarian cancer experience is limited. We documented the prevalence and trajectories of symptoms after first-line chemotherapy using the Measure of Ovarian Symptoms and Treatment concerns (MOST). METHODS: A total of 726 patients who received platinum-based chemotherapy for ovarian cancer were asked to complete the MOST every 3 months, beginning 6 months post-diagnosis and continuing for up to 4 years. We used descriptive statistics to examine temporal changes in MOST-S26 index scores for disease or treatment-related (MOST-DorT), neurotoxicity (MOST-NTx), abdominal (MOST-Abdo), and psychological (MOST-Psych) symptoms, and wellbeing (MOST-Wellbeing) and selected individual symptoms. We used group-based trajectory models to identify groups with persistently poor symptoms. RESULTS: The median MOST-Abdo, MOST-DorT and MOST-Wellbeing score were worst at chemotherapy-end but improved and stabilised by 1, 3 and 12 months after treatment, respectively. The median MOST-NTx score peaked at 1 month after treatment before improving, while the median MOST-Psych score did not change substantially over time. Long-term moderate-to-severe fatigue (32%), trouble sleeping (31%), sore hands and feet (21%), pins and needles (20%) and anxiety (18%) were common. Trajectory models revealed groups of patients with persistent symptoms had MOST-DorT scores above 30 and MOST-NTx scores above 40 at treatment-end. CONCLUSIONS: Although many patients report improvements in symptoms by 3 months after first-line chemotherapy for ovarian cancer, patients who score > 30/100 on MOST-S26-DorT or > 40/100 on MOST-S26-NTx at the end of chemotherapy are likely to have persistent symptoms. The MOST could triage this at-risk subset for early intervention.

Efficacy of dexamethasone in the management of malignant small bowel obstruction in advanced epithelial ovarian cancer.

INTRODUCTION: Malignant small bowel obstruction (MSBO) occurs in up to 50% of women with advanced epithelial ovarian cancer (EOC) causing symptom burden and distress to women and their families, particularly in the terminal stages of the disease. Corticosteroids are used to promote symptom resolution in malignant small bowel obstruction (MSBO) related to EOC, with little published data on their efficacy, optimal dosing and duration of treatment. OBJECTIVE: To evaluate the efficacy of dexamethasone in achieving symptom control in women with advanced EOC presenting with MSBO, assess dexamethasone dosing and efficacy over subsequent presentations, and examine differences in dexamethasone responsiveness between platinum-resistant and platinum-sensitive patient. METHODS: This is a retrospective cohort study of women presenting with MSBO due to advanced EOC over a 12-year period from January 2005 to December 2016 in a single tertiary hospital. RESULTS: Ninety-one women with MSBO were administered dexamethasone over 154 admissions with 89% of women initially achieving partial or complete symptom control. Dexamethasone responsiveness did not change with recurrent admissions, and platinum responsive patients were more likely to respond to dexamethasone than platinum-resistant patients (OR 3.6 [95%CI 1.1 to 12.2, p = 0.04]). A total of 15.6% of patients required additional measures to control symptoms of MSBO, and 44.8% had adequate symptom resolution to allow them to remain on or commence further treatment for EOC. CONCLUSION: Dexamethasone therapy is a useful adjunctive therapy in the management of symptoms associated with MSBO in women with EOC.

Hybridization increases population variation during adaptive radiation.

Adaptive radiations are prominent components of the world's biodiversity. They comprise many species derived from one or a small number of ancestral species in a geologically short time that have diversified into a variety of ecological niches. Several authors have proposed that introgressive hybridization has been important in the generation of new morphologies and even new species, but how that happens throughout evolutionary history is not known. Interspecific gene exchange is expected to have greatest impact on variation if it occurs after species have diverged genetically and phenotypically but before genetic incompatibilities arise. We use a dated phylogeny to infer that populations of Darwin's finches in the Galápagos became more variable in morphological traits through time, consistent with the hybridization hypothesis, and then declined in variation after reaching a peak. Some species vary substantially more than others. Phylogenetic inferences of hybridization are supported by field observations of contemporary hybridization. Morphological effects of hybridization have been investigated on the small island of Daphne Major by documenting changes in hybridizing populations of Geospiza fortis and Geospiza scandens over a 30-y period. G. scandens showed more evidence of admixture than G. fortis Beaks of G. scandens became progressively blunter, and while variation in length increased, variation in depth decreased. These changes imply independent effects of introgression on 2, genetically correlated, beak dimensions. Our study shows how introgressive hybridization can alter ecologically important traits, increase morphological variation as a radiation proceeds, and enhance the potential for future evolution in changing environments.

Adult sex ratio influences mate choice in Darwin's finches.

The adult sex ratio (ASR) is an important property of populations. Comparative phylogenetic analyses have shown that unequal sex ratios are associated with the frequency of changing mates, extrapair mating (EPM), mating system and parental care, sex-specific survival, and population dynamics. Comparative demographic analyses are needed to validate the inferences, and to identify the causes and consequences of sex ratio inequalities in changing environments. We tested expected consequences of biased sex ratios in two species of Darwin's finches in the Galápagos, where annual variation in rainfall, food supply, and survival is pronounced. Environmental perturbations cause sex ratios to become strongly male-biased, and when this happens, females have increased opportunities to choose high-quality males. The choice of a mate is influenced by early experience of parental morphology (sexual imprinting), and since morphological traits are highly heritable, mate choice is expressed as a positive correlation between mates. The expected assortative mating was demonstrated when the Geospiza scandens population was strongly male-biased, and not present in the contemporary Geospiza fortis population with an equal sex ratio. Initial effects of parental imprinting were subsequently overridden by other factors when females changed mates, some repeatedly. Females of both species were more frequently polyandrous in male-biased populations, and fledged more offspring by changing mates. The ASR ratio indirectly affected the frequency of EPM (and hybridization), but this did not lead to social mate choice. The study provides a strong demonstration of how mating patterns change when environmental fluctuations lead to altered sex ratios through differential mortality.

Out-of-pocket and private pay in clinical genetic testing: A scoping review.

Full coverage of the cost of clinical genetic testing is not always available through public or private insurance programs, or a public healthcare system. Consequently, some patients may be faced with the decision of whether to finance testing out-of-pocket (OOP), meet OOP expenses required by their insurer, or not proceed with testing. A scoping review was conducted to identify literature associated with patient OOP and private pay in clinical genetic testing. Seven databases (EMBASE, MEDLINE, CINAHL, PsychINFO, PAIS, the Cochrane Database of Systematic Reviews, and the JBI Evidence-Based Practice database) were searched, resulting in 83 unique publications included in the review. The presented evidence includes a descriptive analysis, followed by a narrative account of the extracted data. Results were divided into four groups according to clinical indication: (1) hereditary breast and ovarian cancer, (2) other hereditary cancers, (3) prenatal testing, (4) other clinical indications. The majority of studies focused on hereditary cancer and prenatal genetic testing. Overall trends indicated that OOP costs have fallen and payer coverage has improved, but OOP expenses continue to present a barrier to patients who do not qualify for full coverage.

A randomised controlled trial to assess the antithrombotic effects of aspirin in type 1 diabetes: role of dosing and glycaemic control.

BACKGROUND: The enhanced thrombotic milieu in diabetes contributes to increased risk of vascular events. Aspirin, a key antiplatelet agent, has inconsistent effects on outcomes in diabetes and the best dosing regimen remains unclear. This work investigated effects of aspirin dose and interaction with glycaemia on both the cellular and protein components of thrombosis. METHODS: A total of 48 participants with type 1 diabetes and 48 healthy controls were randomised to receive aspirin 75 or 300 mg once-daily (OD) in an open-label crossover study. Light transmittance aggregometry and fibrin clot studies were performed before and at the end of each treatment period. RESULTS: Aspirin demonstrated reduced inhibition of collagen-induced platelet aggregation (PA) in participants with diabetes compared with controls, although the higher dose showed better efficacy. Higher aspirin dose facilitated clot lysis in controls but not individuals with diabetes. Collagen-induced PA correlated with glycaemic control, those in the top HbA1c tertile having a lesser inhibitory effect of aspirin. Threshold analysis suggested HbA1c levels of > 65 mmol/mol and > 70 mmol/mol were associated with poor aspirin response to 75 and 300 mg daily doses, respectively. Higher HbA1c was also associated with longer fibrin clot lysis time. CONCLUSIONS: Patients with diabetes respond differently to the antiplatelet and profibrinolytic effects of aspirin compared with controls. In particular, those with elevated HbA1c have reduced inhibition of PA with aspirin. Our findings indicate that reducing glucose levels improves the anti-thrombotic action of aspirin in diabetes, which may have future clinical implications. TRIAL REGISTRATION: EudraCT, 2008-007875-26, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2008-007875-26 .

A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial.

BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

Evolution of Darwin's finches and their beaks revealed by genome sequencing.

Darwin's finches, inhabiting the Galápagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives. Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis), a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and, thereby, to an expanded utilization of food resources.

Role of sexual imprinting in assortative mating and premating isolation in Darwin's finches.

Global biodiversity is being degraded at an unprecedented rate, so it is important to preserve the potential for future speciation. Providing for the future requires understanding speciation as a contemporary ecological process. Phylogenetically young adaptive radiations are a good choice for detailed study because diversification is ongoing. A key question is how incipient species become reproductively isolated from each other. Barriers to gene exchange have been investigated experimentally in the laboratory and in the field, but little information exists from the quantitative study of mating patterns in nature. Although the degree to which genetic variation underlying mate-preference learning is unknown, we provide evidence that two species of Darwin's finches imprint on morphological cues of their parents and mate assortatively. Statistical evidence of presumed imprinting is stronger for sons than for daughters and is stronger for imprinting on fathers than on mothers. In combination, morphology and species-specific song learned from the father constitute a barrier to interbreeding. The barrier becomes stronger the more the species diverge morphologically and ecologically. It occasionally breaks down, and the species hybridize. Hybridization is most likely to happen when species are similar to each other in adaptive morphological traits, e.g., body size and beak size and shape. Hybridization can lead to the formation of a new species reproductively isolated from the parental species as a result of sexual imprinting. Conservation of sufficiently diverse natural habitat is needed to sustain a large sample of extant biota and preserve the potential for future speciation.

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

BACKGROUND: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). AIMS: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. MATERIALS AND METHODS: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. MAIN OUTCOME MEASURES: The primary outcome of the study was histological confirmation of HSIL. RESULTS: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. CONCLUSIONS: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

The clinical management of orthodontically-induced external root resorption: A questionnaire survey.

INTRODUCTION: With more dentists performing orthodontics, identifying and managing patients at risk or affected by orthodontically-induced external root resorption (OIERR) is paramount. METHODS: This study, conducted according to STROBE (STrengthening the Reporting of OBservational studies in Epidemiology), studied Australian orthodontists. Orthodontists were asked to complete a clinical questionnaire evaluating their diagnostic and management approaches to OIERR. RESULTS: Orthodontists most commonly use a history of previous root resorption and the use of an orthopantomogram to screen and monitor patients. An orthopantomogram is used either 6 months for those identified as at risk of OIERR or 10-12 months for those who are not. Once detected, most orthodontists will record OIERR in terms of severity. If severe root resorption was detected, orthodontists would compromise on the treatment outcome and promptly complete treatment; if extraction sites remain closed, most orthodontists will interrupt treatment for 3-6 months. After treatment, orthodontists' retention protocol is unchanged regardless of OIERR experience. Treatment planning for patients with generalized OIERR before treatment (P = 0.002) was the only decision shown to be associated with years of clinical experience (P >0.05). CONCLUSIONS: It is shown that no 1 method for managing OIERR exists, with most orthodontists arguing patient specificity to treatment modality. The various selected clinical approaches accurately reflect the current state of scientific literature on the topic.

A healthy lifestyle and survival among women with ovarian cancer.

Ovarian cancer has a poor survival rate and, understandably, women often want to know whether there is anything they can do to improve their prognosis. Our goal was to investigate the association between a healthy lifestyle prediagnosis and postdiagnosis and survival in a cohort of Australian women with invasive epithelial ovarian cancer. We calculated a healthy lifestyle index (HLI) based on women's self-reported smoking status, height, weight, physical activity, diet and alcohol consumption before diagnosis (n = 678) and after completing primary treatment (n = 512). Clinical data and vital status for each woman were ascertained through medical records. Cox proportional hazards regression was conducted to calculate hazard ratios (HR) and 95% confidence interval (CI) for all-cause mortality. There was a suggestive association between a more healthy lifestyle before diagnosis and better survival (HR 0.79, 95% CI: 0.59-1.04), however, the association was stronger for lifestyle after diagnosis, with women in the highest tertile having significantly better survival than women in the lowest tertile (HR 0.61, 95% CI: 0.40-0.93; P-trend = .02). Current smoking, particularly postdiagnosis, was associated with higher mortality (HR 1.68, 95% CI: 1.17-2.42; HR 2.82, 95% CI: 1.29-6.14, for prediagnosis and postdiagnosis smoking, respectively), but women who quit after diagnosis had survival outcomes similar to nonsmokers (HR 0.99, 95% CI: 0.57-1.72). Higher physical activity after diagnosis was associated with better survival (HR 0.60, 95% CI: 0.39-0.92; P-trend = .02). A healthy lifestyle after diagnosis, in particular not smoking and being physically active, may help women with ovarian cancer improve their prognosis.

Gene flow, ancient polymorphism, and ecological adaptation shape the genomic landscape of divergence among Darwin's finches.

Genomic comparisons of closely related species have identified "islands" of locally elevated sequence divergence. Genomic islands may contain functional variants involved in local adaptation or reproductive isolation and may therefore play an important role in the speciation process. However, genomic islands can also arise through evolutionary processes unrelated to speciation, and examination of their properties can illuminate how new species evolve. Here, we performed scans for regions of high relative divergence (FST) in 12 species pairs of Darwin's finches at different genetic distances. In each pair, we identify genomic islands that are, on average, elevated in both relative divergence (FST) and absolute divergence (dXY). This signal indicates that haplotypes within these genomic regions became isolated from each other earlier than the rest of the genome. Interestingly, similar numbers of genomic islands of elevated dXY are observed in sympatric and allopatric species pairs, suggesting that recent gene flow is not a major factor in their formation. We find that two of the most pronounced genomic islands contain the ALX1 and HMGA2 loci, which are associated with variation in beak shape and size, respectively, suggesting that they are involved in ecological adaptation. A subset of genomic island regions, including these loci, appears to represent anciently diverged haplotypes that evolved early during the radiation of Darwin's finches. Comparative genomics data indicate that these loci, and genomic islands in general, have exceptionally low recombination rates, which may play a role in their establishment.