A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Formation and loss of metastable brucite: does Fe(II)-bearing brucite support microbial activity in serpentinizing ecosystems?

Ultramafic rocks undergo successive stages of hydration and oxidation during water/rock interaction, giving rise to secondary minerals such as brucite, serpentine, magnetite and the production of H2(g). Ferroan brucite (MgxFe(1-x)2+(OH)2) often forms under low water/rock ratios early during the 'serpentinization' process. The formation of ferroan brucite sequesters Fe(II) and suppresses the production of H2, thereby limiting the flux of reductants suitable for sustaining microbial metabolism. Yet ferroan brucite is a relatively soluble mineral 'reservoir' for reactive Fe(II). Brucite is often metastable and can be lost at later stages of peridotite hydration when there is a significant increase in the water/rock ratio or the activity of SiO2 or CO2. The Fe(OH)2 component of brucite has the thermodynamic potential to reduce most aqueous oxidants. Therefore, ferroan brucite may reduce water and/or dissolved carbon, nitrogen and sulfur species, while the Fe(II) is converted into more stable secondary minerals such as Fe(II/III)-oxides and hydroxides (e.g. green-rust, magnetite, iowaite and pyroaurite) and ferric serpentine. The reactivity of ferroan brucite, and the associated rate of Fe solubilization and oxidation in subsurface fluids, could be a key regulator on the rate of electron transfer from serpentinites to the rock-hosted biosphere. Aqueous alteration of ferroan brucite may significantly modulate the H2 activity in fluids circulating within partially serpentinized rocks, and buffer H2 as it is lost by advection or in situ consumption by a hydrogenotrophic microbial community. Moreover, there may be microbial organisms that specifically colonize and use ferroan brucite as an electron donor for their metabolism. The energy fluxes sustained by localized brucite oxidation may often be sufficiently large to sustain abundant microbial communities; water/rock reaction zones where brucite is consumed could serve as environments to search for extant or fossil serpentinite-hosted life. This article is part of a discussion meeting issue 'Serpentinite in the Earth System'.

Development and validation of a prognostic model for overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer.

Background: Prognostic models are needed that reflect contemporary practice for men with metastatic castration-resistant prostate cancer (mCRPC). We sought to identify predictive and prognostic variables for overall survival (OS) in chemotherapy-naïve men with mCRPC treated with enzalutamide. Patients and methods: Patients from the PREVAIL trial database (enzalutamide versus placebo) were randomly split 2 : 1 into training (n = 1159) and testing (n = 550) sets. Using the training set, 23 predefined variables were analyzed and a multivariable model predicting OS was developed and validated in an independent testing set. Results: Patient characteristics and outcomes were well balanced between training and testing sets; median OS was 32.7 months in each. The final validated multivariable model included 11 independent prognostic variables. Median OS for low-, intermediate-, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5-NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14-0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and progression differed widely in model-defined risk groups. Enzalutamide improved outcomes in all prognostic risk groups. Conclusions: Our validated prognostic model incorporates variables routinely collected in chemotherapy-naïve men with mCRPC treated with enzalutamide, identifying subsets of patients with widely differing survival outcomes that provide useful information for external validation, patient care, and clinical trial design. Trial registration: ClinicalTrials.gov: NCT01212991.

Parallel habitat acclimatization is realized by the expression of different genes in two closely related salamander species (genus Salamandra).

The utilization of similar habitats by different species provides an ideal opportunity to identify genes underlying adaptation and acclimatization. Here, we analysed the gene expression of two closely related salamander species: Salamandra salamandra in Central Europe and Salamandra infraimmaculata in the Near East. These species inhabit similar habitat types: 'temporary ponds' and 'permanent streams' during larval development. We developed two species-specific gene expression microarrays, each targeting over 12 000 transcripts, including an overlapping subset of 8331 orthologues. Gene expression was examined for systematic differences between temporary ponds and permanent streams in larvae from both salamander species to establish gene sets and functions associated with these two habitat types. Only 20 orthologues were associated with a habitat in both species, but these orthologues did not show parallel expression patterns across species more than expected by chance. Functional annotation of a set of 106 genes with the highest effect size for a habitat suggested four putative gene function categories associated with a habitat in both species: cell proliferation, neural development, oxygen responses and muscle capacity. Among these high effect size genes was a single orthologue (14-3-3 protein zeta/YWHAZ) that was downregulated in temporary ponds in both species. The emergence of four gene function categories combined with a lack of parallel expression of orthologues (except 14-3-3 protein zeta) suggests that parallel habitat adaptation or acclimatization by larvae from S. salamandra and S. infraimmaculata to temporary ponds and permanent streams is mainly realized by different genes with a converging functionality.

Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR), proposed as an indicator of cancer-related inflammation, has known prognostic value in prostate cancer. We examine its association with survival (OS) and response in patients treated with second-line chemotherapy. METHODS: We analysed patients with metastatic castration-resistant prostate cancer (mCRPC) treated in the TROPIC trial, evaluating cabazitaxel versus mitoxantrone. Cox regression models were used to investigate the association of baseline NLR (BLNLR) with OS and the significance of a change in NLR count with treatment. Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen (PSA) and RECIST responses. The optimal NLR cut-off was established based on the concordance index of different values. RESULTS: Data from 755, 654 and 405 patients was available for OS, PSA and RECIST response analysis respectively. Median OS was 14.0 months [95% confidence interval (CI) 13.2-14.8]. Median NLR was 2.9 (IQR: 1.9-5.1). BLNLR was associated with survival (HR 1.5, 95% CI 1.1-2.1, P = 0.011) in multivariable analysis (MVA) independently of variables included in the Halabi nomogram, treatment arm and corticosteroid use. The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival. BLNLR ≥3.0 was associated with lower PSA response (40.1% versus 59.9%; P < 0.001) and RECIST response (7.7% versus 15.6%, P = 0.022) in MVA. Conversion from high (≥3) to low (<3) NLR was associated with improved survival (HR 0.66; 95% CI 0.51-0.85; P = 0.001) and higher PSA response rates (66.4% versus 33.6%; P = 0.000). Use of corticosteroids at baseline did not modify the association between NLR and survival. CONCLUSIONS: NLR is a valid prognostic biomarker in CRPC and is associated with survival, PSA and RECIST responses in patients treated with second-line chemotherapy. Changes in NLR counts with treatment may indicate benefit. NLR prognostic value is independent of prior use of corticosteroids. CLINICALTRIALSGOV: NCT00417079.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. PATIENTS AND METHODS: Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. RESULTS: In the training set, both dNLR ≥median (2) and duration of initial ADT

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated. METHODS: A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan-Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR. RESULTS: The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12-2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39-2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17-2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR. CONCLUSIONS: Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.

Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone. PATIENTS AND METHODS: All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation. RESULTS: A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%-50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis. CONCLUSIONS: A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.

A population-based cohort study of the effect of Caesarean section on subsequent fertility.

STUDY QUESTION: Is there an association between Caesarean section and subsequent fertility? SUMMARY ANSWER: There is no or only a slight effect of Caesarean section on future fertility. WHAT IS KNOWN ALREADY: Previous studies have reported that delivery by a Caesarean section is associated with fewer subsequent pregnancies and longer inter-pregnancy intervals. The interpretation of these findings is difficult because of significant weaknesses in study designs and analytical methods, notably the potential effect of the indication for Caesarean section on subsequent delivery. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 1 047 644 first births to low-risk women using routinely collected, national administrative data of deliveries in English maternity units between 1 April 2000 and 31 March 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primiparous women aged 15-40 years who had a singleton, term, live birth in the English National Health Service were included. Women with high-risk pregnancies involving placenta praevia, pre-eclampsia, eclampsia (gestational or pre-existing), hypertension or diabetes were excluded from the main analysis. Kaplan-Meier analyses and Cox proportional hazard models were used to assess the effect of mode of delivery on time to subsequent birth, adjusted for age, ethnicity, socio-economic deprivation and year of index delivery. MAIN RESULTS AND THE ROLE OF CHANCE: Among low-risk primiparous women, 224 024 (21.4%) were delivered by Caesarean section. The Kaplan-Meier estimate of the subsequent birth rate at 10 years for the cohort was 74.7%. Compared with vaginal delivery, subsequent birth rates were marginally lower after elective Caesarean for breech (adjusted hazard ratio, HR 0.96, 95% CI 0.94-0.98). Larger effects were observed after elective Caesarean for other indications (adjusted HR 0.81, 95% CI 0.78-0.83), and emergency Caesarean (adjusted HR 0.91, 95% CI 0.90-0.93). The effect was smallest for elective Caesarean for breech, and this was not statistically significant in women younger than 30 years of age (adjusted HR 0.98, 95% CI 0.96-1.01). LIMITATIONS, REASONS FOR CAUTION: We used birth cohorts from maternity units with good quality parity information. The data are likely to be nationally representative because the characteristics of the deliveries in included and omitted units were similar. There may be residual bias in our adjusted results due to unmeasured maternal factors such as obesity and voluntary absence of conception. Any residual bias would lead to an overestimate of the effect of Caesarean section on fertility, and the true effect is therefore likely to be smaller than the effect reported in our study. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide strong evidence that there is no or only a slight effect of Caesarean section on future fertility. The clinical and social circumstances leading to the Caesarean section have a greater effect on future fertility than the Caesarean section itself. This finding is important in light of rising Caesarean section rates. STUDY FUNDING/COMPETING INTEREST(S): IG-U is supported by the Lindsay Stewart R&D Centre, Royal College of Obstetricians and Gynaecologists, UK. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: n/a.

Translating clinical trials to clinical practice: outcomes of men with metastatic castration resistant prostate cancer treated with docetaxel and prednisone in and out of clinical trials.

BACKGROUND: Multiple factors can influence outcomes of patients receiving identical interventions in clinical trials and in routine practice. Here, we compare outcomes of men with metastatic castrate-resistant prostate cancer (mCRPC) treated with docetaxel and prednisone in routine practice and in clinical trials. PATIENTS AND METHODS: We reviewed patients with mCRPC treated with docetaxel at Princess Margaret Cancer Centre. Primary outcomes were overall survival and PSA response rate. Secondary outcomes were reasons for discontinuation and febrile neutropenia. Outcomes were compared for men treated in routine practice and in clinical trials, and with data from the TAX 327 study. RESULTS: From 2001 to 2011, 438 men were treated, of whom 357 received 3-weekly docetaxel as first-line chemotherapy: 314 in routine practice and 43 in clinical trials. Trial patients were younger and had better performance status. Median survival was 13.6 months [95% confidence interval (95% CI) 12.1-15.1 months] in routine practice and 20.4 months (95% CI 17.4-23.4 months, P = 0.007) within clinical trials, compared with 19.3 months (95% CI 17.6-21.3 months, P < 0.001) in the TAX 327 study. PSA response rates were 45%, 54%, and 53%, respectively (P = NS). Reasons for treatment discontinuation were similar although trial patients received more cycles (median: 6 versus 8 versus 9.5, P < 0.001). Rates of febrile neutropenia were 9.6, 0, and 3% (P < 0.001) while rates of death within 30 days of last dose were 4%, 0%, and 3%, respectively (P = NS). CONCLUSIONS: Survival of patients with mCRPC treated with docetaxel in routine practice is shorter than for men included in trials and is associated with more toxicity.

Impact of Caesarean section on subsequent fertility: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between a Caesarean section and subsequent fertility? SUMMARY ANSWER: Most studies report that fertility is reduced after Caesarean section compared with vaginal delivery. However, studies with a more robust design show smaller effects and it is uncertain whether the association is causal. WHAT IS KNOWN ALREADY: A previous systematic review published in 1996 summarizing six studies including 85 728 women suggested that Caesarean section reduces subsequent fertility. The included studies suffer from severe methodological limitations. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis of cohort studies comparing subsequent reproductive outcomes of women who had a Caesarean section with those who delivered vaginally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of Cochrane Library, Medline, Embase, CINAHL Plus and Maternity and Infant Care databases were conducted in December 2011 to identify randomized and non-randomized studies that compared the subsequent fertility outcomes after a Caesarean section and after a vaginal delivery. Eighteen cohort studies including 591 850 women matched the inclusion criteria. Risk of bias was assessed by the Newcastle-Ottawa scale (NOS). Data extraction was done independently by two reviewers. The meta-analysis was based on a random-effects model. Subgroup analyses were performed to assess whether the estimated effect was influenced by parity, risk adjustment, maternal choice, cohort period, and study quality and size. MAIN RESULTS AND THE ROLE OF CHANCE: The impact of Caesarean section on subsequent pregnancies could be analysed in 10 studies and on subsequent births in 16 studies. A meta-analysis suggests that patients who had undergone a Caesarean section had a 9% lower subsequent pregnancy rate [risk ratio (RR) 0.91, 95% confidence interval (CI) (0.87, 0.95)] and 11% lower birth rate [RR 0.89, 95% CI (0.87, 0.92)], compared with patients who had delivered vaginally. Studies that controlled for maternal age or specifically analysed primary elective Caesarean section for breech delivery, and those that were least prone to bias according to the NOS reported smaller effects. LIMITATIONS, REASONS FOR CAUTION: There is significant variation in the design and methods of included studies. Residual bias in the adjusted results is likely as no study was able to control for a number of important maternal characteristics, such as a history of infertility or maternal obesity. WIDER IMPLICATIONS OF THE FINDINGS: Further research is needed to reduce the impact of selection bias by indication through creating more comparable patient groups and applying risk adjustment.

Rates of subsequent surgery following endometrial ablation among English women with menorrhagia: population-based cohort study.

OBJECTIVE: To assess the risk of further surgery amongst women who had an initial endometrial ablation (EA) for the treatment of heavy menstrual bleeding (HMB). DESIGN: A retrospective cohort study using a national administrative database. SETTING: Population-based study of hospital care in the English National Health Service. POPULATION: A cohort of 114,910 women who had EA for HMB between January 2000 and December 2011. METHODS: Multiple Cox regressions were performed to identify the risks of a further procedure, adjusted for age, social deprivation, year and type of initial EA, and presence of fibroids/polyps. MAIN OUTCOME MEASURES: Time to repeat EA or hysterectomy after initial surgery. RESULTS: Of 114,910 women undergoing EA, 16.7% had at least one subsequent procedure within 5 years. Higher rates of subsequent surgery were associated with younger age at initial EA, with women aged under 35 years having an adjusted hazard ratio of 2.83 (95% CI 2.67-2.99), compared with women aged over 45 years. Women who had radiofrequency ablation were less likely to have subsequent surgery as compared with first-generation techniques (HR 0.69, 95% CI 0.63-0.76). The rate of a subsequent hysterectomy within 5 years was 13.5%. Younger women (OR 0.59, 95% CI 0.51-0.69) and those who had balloon, microwave, or radiofrequency ablation were less likely to have a second EA procedure, rather than a hysterectomy. CONCLUSIONS: One in six women have further surgery after EA for HMB, which is a higher rate than reported in clinical trials. This risk of further surgery decreases with age.

Third- and fourth-degree perineal tears among primiparous women in England between 2000 and 2012: time trends and risk factors.

OBJECTIVE: To describe the trends of severe perineal tears in England and to investigate to what extent the changes in related risk factors could explain the observed trends. DESIGN: A retrospective cohort study of singleton deliveries from a national administrative database. SETTING: The English National Health Service between 1 April 2000 and 31 March 2012. POPULATION: A cohort of 1 035 253 primiparous women who had a singleton, term, cephalic, vaginal birth. METHODS: Multivariable logistic regression was used to estimate the impact of financial year of birth (labelled by starting year), adjusting for major risk factors. MAIN OUTCOME MEASURE: The rate of third-degree (anal sphincter is torn) or fourth-degree (anal sphincter as well as rectal mucosa are torn) perineal tears. RESULTS: The rate of reported third- or fourth-degree perineal tears tripled from 1.8 to 5.9% during the study period. The rate of episiotomy varied between 30 and 36%. An increasing proportion of ventouse deliveries (from 67.8 to 78.6%) and non-instrumental deliveries (from 15.1 to 19.1%) were assisted by an episiotomy. A higher risk of third- or fourth-degree perineal tears was associated with a maternal age above 25 years, instrumental delivery (forceps and ventouse), especially without episiotomy, Asian ethnicity, a more affluent socio-economic status, higher birthweight, and shoulder dystocia. CONCLUSIONS: Changes in major risk factors are unlikely explanations for the observed increase in the rate of third- or fourth-degree tears. The improved recognition of tears following the implementation of a standardised classification of perineal tears is the most likely explanation.

How distant? An experimental analysis of students' COVID-19 exposure and physical distancing in university buildings.

Closed university buildings proved to be one of the main hot spots for virus transmission during pandemics. As shown during the COVID-19 pandemic, physical distancing is one of the most effective measures to limit such transmission. As universities prepare to manage in-class activities, students' adherence to physical distancing requirements is a priority topic. Unfortunately, while physical distancing in classrooms can be easily managed, the movement of students inside common spaces can pose high risk of close proximity. This paper provides an experimental analysis of unidirectional student movement inside a case-study university building to investigate how physical distancing requirements impact student movement and grouping behaviour. Results show general adherence with the minimum required physical distancing guidance, but spaces such as corridors pose higher risk of exposure than doorways. Doorway width, in combination with group behaviour, affect the students' capacity to keep the recommended physical distance. Furthermore, questionnaire results show that students report higher perceived vulnerability while moving along corridors. Evidence-based results can support decision-makers in understanding individuals' exposure to COVID-19 in universities and researchers in developing behavioural models in preparation of future outbreaks and pandemics.

Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective?

BACKGROUND: First-line treatments for unexplained infertility traditionally include clomifene citrate (CC) or unstimulated intrauterine insemination (IUI). A recently published randomized controlled trial considered the effectiveness of CC and IUI in patients with unexplained infertility and found that neither treatment offered a superior live birth rate when compared with expectant management (EM). This paper reports the economic evaluation conducted alongside this trial in order to assess whether health care providers are gaining value for money in this clinical area. METHODS: Five hundred and eighty women across five Scottish hospitals were randomized to either EM, CC or IUI for 6 months. The primary outcome measure was live births. Resource-use data were collected during the trial and costs were calculated from a UK National Health Service (NHS) perspective. Incremental cost-effectiveness ratios were calculated, expressed as cost per live birth, in order to compare the cost-effectiveness of CC and IUI with that of EM to treat unexplained infertility. RESULTS: Live birth rates in the three randomized groups were: EM = 32/193 (17%), CC = 26/194 (13%) and IUI = 43/193 (22%). The mean (standard deviation) costs per treatment cycle were £0 for EM, £83 (£17) for CC and £98 (£31) for IUI. The mean treatment costs per patient for EM, CC and IUI were £12 (£117), £350 (£220) and £331 (£222), respectively. The cost per live birth for EM, CC and IUI was £72 (95% confidence interval £0-£206), £2611 (£1870-£4166) and £1487 (£1116-£2155), respectively. The incremental cost-effectiveness ratio for IUI versus EM was £5604 (-£12204 to £2227), with CC dominated by IUI. CONCLUSIONS: Despite being more expensive, existing treatments such as empirical CC and unstimulated IUI do not offer superior live birth rates compared with EM of unexplained infertility. They are unlikely to be a cost-effective use of limited NHS resources. The study's main limitation is that it did not consider the psychological effects on couples. ISRCT Number: 71762042.

Microscale imaging and identification of Fe speciation and distribution during fluid-mineral reactions under highly reducing conditions.

The oxidation state, speciation, and distribution of Fe are critical determinants of Fe reactivity in natural and engineered environments. However, it is challenging to follow dynamic changes in Fe speciation in environmental systems during progressive fluid-mineral interactions. Two common geological and aquifer materials-basalt and Fe(III) oxides-were incubated with saline fluids at 55 °C under highly reducing conditions maintained by the presence of Fe(0). We tracked changes in Fe speciation after 48 h (incipient water-rock reaction) and 10 months (extensive water-rock interaction) using synchrotron-radiation µXRF maps collected at multiple energies (ME) within the Fe K-edge. Immediate PCA analysis of the ME maps was used to optimize µXANES analyses; in turn, refitting the ME maps with end-member XANES spectra enabled us to detect and spatially resolve the entire variety of Fe-phases present in the system. After 48 h, we successfully identified and mapped the major Fe-bearing components of our samples (Fe(III) oxides, basalt, and rare olivine), as well as small quantities of incipient brucite associated with olivine. After 10 months, the Fe(III)-oxides remained stable in the presence of Fe(0), whereas significant alteration of basalt to minnesotaite and chlinochlore had occurred, providing new insights into heterogeneous Fe speciation in complex geological media under highly reducing conditions.

The epidemiology of infertility in the North East of Scotland.

BACKGROUND: There is a perception that the prevalence of infertility is on the rise. This study aimed to determine the current prevalence of infertility in a defined geographical population, ascertain changes in self-reported infertility over time and identify risk factors associated with infertility. METHODS: A postal questionnaire survey of a random population-based sample of women aged 31-50 years was performed in the Grampian region of Scotland. Questions addressed the following areas: pregnancy history, length of time taken to become pregnant each time, whether medical advice had been sought and self-reported exposure to factors associated with infertility. RESULTS: Among 4466 women who responded, 400 (9.0%) [95% CI 8.1, 9.8] had chosen not to have children. Of the remaining 4066 women, 3283 (80.7%) [95% CI 79.5, 82.0] reported no difficulties in having children and the remaining 783 (19.3%) [95% CI 18.1, 20.5] had experienced infertility, defined as having difficulty in becoming pregnant for more than 12 months and/or seeking medical advice. In total 398 (9.8%) [95% CI 8.9, 10.7] women had primary infertility, 285 (7.0%) [95% CI 6.2, 7.8] had secondary infertility, 100 (2.5%) [95% CI 2.0, 2.9] had primary as well as secondary infertility. A total of 342 (68.7%) and 208 (73.0%) women with primary and secondary infertility, respectively, sought medical advice and 202 (59.1%) and 118 (56.7%) women in each group subsequently conceived. History of pelvic surgery, Chlamydial infection, endometriosis, chemotherapy, long-term health problems and obesity were associated with infertility. In comparison with a similar survey of women aged 46-50 from the same geographical area, the prevalence of both primary infertility (>24 months) [70/1081, (6.5%) versus 68/710 (9.6%) P = 0.02] and secondary infertility [29/1081 (2.7%) versus 40/710 (5.6%) P = 0.002] were significantly lower. CONCLUSIONS: Nearly one in five women attempting conception sampled in this study experienced infertility, although over half of them eventually conceived. Fertility problems were associated with endometriosis, Chlamydia trachomatis infection and pelvic surgery, as well as obesity, chemotherapy and some long-term chronic medical conditions. There is no evidence of an increase in the prevalence of infertility in this population over the past 20 years.

Behavioral phylogenies and the direction of evolution.

A model for using mate preference data to deduce the direction of evolution between populations related by founder events or population bottlenecks is examined. Data from a wide range of organisms satisfying the necessary constraints of population structure are compatible with the model developed by K. Y. Kaneshiro from studies of Hawaiian Drosophila.