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Background: Endometrioma are endometriotic deposits within the ovary. Laparoscopic management of endometriomas is associated with shorter hospital stay, faster recovery, and decreased hospital costs compared with laparotomy. The previous version of this systematic review (2008), including randomised controlled trials (RCTs) of surgical interventions for endometrioma, concluded that laparoscopic cystectomy (excision) was preferable to drainage and ablation of endometrioma. We aimed to update the evidence comparing excision with drainage and ablation for improving pain and fertility-related outcomes., Objectives: To evaluate the safety and efficacy of laparoscopic excision (cystectomy) compared with laparoscopic drainage and ablation of endometrioma in women of reproductive age., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycInfo, two trials registries, grey literature sources, and conference proceedings on 19 December 2022. We also checked the reference lists of relevant papers and contacted leaders in the field of endoscopic surgery for any additional trials., Selection Criteria: Eligible studies were RCTs that compared excision with drainage and ablation of endometriomas., Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data, assessed risk of bias, and applied the GRADE approach to rate the certainty of evidence., Main Results: We identified nine studies (involving 578 women) that investigated laparoscopic excision versus drainage and ablation of endometriomas measuring at least 3 cm in diameter. Participants were women of reproductive age who presented to an outpatient gynaecology clinic with pain, infertility, or both. For most outcomes, we downgraded the certainty of evidence for risk of bias due to lack of blinding and for imprecision due to low participant numbers. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dysmenorrhoea recurrence (OR 0.25, 95% CI 0.12 to 0.52; 2 studies, 140 women; low-certainty evidence;). Recurrence of dysmenorrhoea may occur in 49% of women after ablative surgery compared with 10% to 34% after excisional surgery. At up to two years after surgery, excisional surgery compared with ablative surgery may reduce the risk of dyspareunia recurrence (OR 0.09, 95% CI 0.03 to 0.22; 2 studies, 131 women; low-certainty evidence). Recurrence of dyspareunia may occur in 58% of women after ablative surgery compared with 4% to 23% after excisional surgery. At one year after surgery, excisional surgery may reduce the risk of endometrioma recurrence compared with ablative surgery (OR 0.17, 95% CI 0.09 to 0.34; 4 studies, 264 women; low-certainty evidence). Recurrence of endometrioma may occur in 37% of women after ablative surgery compared with 5% to 17% after excisional surgery. At one year after surgery, excisional surgery may reduce the need for further endometrioma surgery compared with ablative surgery (OR 0.16, 95% CI 0.07 to 0.41; 2 studies, 178 women; low-certainty evidence). Our results suggest that 32% of women require further endometrioma surgery after ablative surgery compared with 3% to 16% after excisional surgery. There may be little or no difference between excisional surgery and ablative surgery in terms of their effect on spontaneous pregnancy during the first year after surgery (OR 1.27, 95% CI 0.33 to 4.87; 3 studies, 101 women; low-certainty evidence). Five studies reported that there were no conversions to laparotomy. No studies provided data about any other surgical complications or adverse effects., Authors' Conclusions: Surgical management of endometrioma with excision (cystectomy) may be more effective than drainage and ablation for reducing painful menstrual periods, pain during sexual intercourse, endometrioma recurrence, and the need for further endometrioma surgery. However, there may be little or no difference between the techniques in their effect on subsequent pregnancy rates. We found limited evidence on the safety of excisional surgery compared with ablative surgery. Future trials should recruit adequate numbers of women and measure outcomes relating to adverse events and clinical pregnancy., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Alcoholics Anonymous (AA) is an established resource for people suffering from alcohol use disorder (AUD). However, Bill Wilson, the co-founder of AA, in his second letter to Jung referred to its low success rate. One evidence-based alternative, dating back to the 1950s, is the clinical use of lysergic acid diethylamide (LSD) for treating AUD. Bill Wilson was a strong advocate of using LSD as a preparation for alcoholics who had difficulty grasping the spiritual aspect of the 12-step programme. Bill Wilson wrote a "secret" four-page letter to Carl Jung detailing his own use of LSD and the success two psychiatrists in Canada had in treating alcoholics and asked for his advice on using LSD to help alcoholics. Aniela Jaffé, a Jungian analyst and co-worker of Jung, replied to Wilson on May 29, 1961, "… as soon as Dr. Jung feels better and has enough strength to begin again his mail, I will show it to him." Jung died a week later. This article quotes Jung's previous hostile opinions on psychedelics and asks: Just as Jung overcame his negative views on groups when giving "complete instructions" on extending the 12-step programme of AA to "general neurotics", might he similarly have changed his mind when he saw the documented success of using LSD with recalcitrant alcoholics?, (© 2024 The Society of Analytical Psychology.)

This paper presents the composite drought indicator (CDI) that Jordanian, Lebanese, Moroccan, and Tunisian government agencies now produce monthly to support operational drought management decision making, and it describes their iterative co-development processes. The CDI is primarily intended to monitor agricultural and ecological drought on a seasonal time scale. It uses remote sensing and modelled data inputs, and it reflects anomalies in precipitation, vegetation, soil moisture, and evapotranspiration. Following quantitative and qualitative validation assessments, engagements with policymakers, and consideration of agencies' technical and institutional capabilities and constraints, we made changes to CDI input data, modelling procedures, and integration to tailor the system for each national context. We summarize validation results, drought modelling challenges and how we overcame them through CDI improvements, and we describe the monthly CDI production process and outputs. Finally, we synthesize procedural and technical aspects of CDI development and reflect on the constraints we faced as well as trade-offs made to optimize the CDI for operational monitoring to support policy decision-making-including aspects of salience, credibility, and legitimacy-within each national context., (© 2024. The Author(s).)

Background: The Emergency Department (ED), while being an integral part of healthcare systems, frequently experiences noise levels surpassing the World Health Organization's recommended thresholds. These excessive noise levels could considerably compromise the safety and wellbeing of both patients and staff., Methods: To evaluate noise levels throughout the ED environment, this study utilized dosimeters to measure noise levels over a 24-hour period in six distinct locations, including the ED Waiting Room and Treatment areas., Results: The study found that noise exceeded the WHO recommendations in all six areas of the ED for the entire 24-hour period. Peak noise levels were recorded up to 102.8 dB, which is as loud as noise levels at a construction site. The ED Waiting Room exhibited high peak and average noise levels, indicating the urgent need for quality improvement efforts. These findings align with the results of previous research, thereby suggesting that noise levels in the ED have remained problematic for more than a decade., Conclusion: The findings of this study underscore the importance of addressing excessive noise levels in the ED to create a safe and therapeutic hospital environment for both patients and staff. Healthcare organizations must implement proactive measures to address excessive noise levels in the ED., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues. Methods: We engineered a tumor-specific bifunctional NIR bioprobe designed to precisely target HNSCC and induce phototheranosis using bioconjugation of a cyclic arginine-glycine-aspartic acid (cRGD) motif and zwitterionic polymethine NIR fluorophore. The cytotoxic effects of cRGD-ZW800-PEG were measured by assessing heat and reactive oxygen species (ROS) generation upon an 808-nm laser irradiation. We then determined the in vivo efficacy of cRGD-ZW800-PEG in the FaDu xenograft mouse model of HNSCC, as well as its biodistribution and clearance, using a customized portable NIR imaging system. Results: Real-time NIR imaging revealed that intravenously administered cRGD-ZW800-PEG targeted tumors rapidly within 4 h postintravenous injection in tumor-bearing mice. Upon laser irradiation, cRGD-ZW800-PEG produced ROS and heat simultaneously and exhibited synergistic photothermal and photodynamic effects on the tumoral tissue without affecting the neighboring healthy tissues. Importantly, all unbound bioprobes were cleared through renal excretion. Conclusions: By harnessing phototheranosis in combination with tailored tumor selectivity, our targeted bioprobe ushers in a promising paradigm in cancer treatment. It promises safer and more efficacious therapeutic avenues against cancer, marking a substantial advancement in the field., Competing Interests: Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. H.S.C. reports a relationship with Nawoo Vision and Ferrex Therapeutics: board membership, stock, and royalty., (Copyright © 2024 Hae Sang Park et al.)

Two of the most pressing challenges facing bioimaging are nonspecific uptake of intravenously administered contrast agents and incomplete elimination of unbound targeted agents from the body. Designing a targeted contrast agent that shows fast clearance from background tissues and eventually the body after complete targeting is key to the success of image-guided interventions. Here, this work describes the development of renally clearable near-infrared contrast agents and their potential use for dual-channel image-guided tumor targeting. cRGD-ZW800-PEG (800 nm channel) and ZW700-PEG (700 nm channel) are able to visualize tumor margins and tumor vasculature simultaneously and respectively. These targeted agents show rapid elimination from the bloodstream, followed by renal clearance, which together significantly lower off-target background signals and potential toxicity. To demonstrate its applicability, this multispectral imaging is performed in various tumor-bearing animal models including lung cancer, pancreatic neuroendocrine tumors, breast, and ovarian cancer., (© 2023 Wiley-VCH GmbH.)

This article presents C3I-SynFace: a large-scale synthetic human face dataset with corresponding ground truth annotations of head pose and face depth generated using the iClone 7 Character Creator "Realistic Human 100" toolkit with variations in ethnicity, gender, race, age, and clothing. The data is generated from 15 female and 15 male synthetic 3D human models extracted from iClone software in FBX format. Five facial expressions - neutral, angry, sad, happy, and scared are added to the face models to add further variations. With the help of these models, an open-source data generation pipeline in Python is proposed to import these models into the 3D computer graphics tool Blender and render the facial images along with the ground truth annotations of head pose and face depth in raw format. The datasets contain more than 100k ground truth samples with their annotations. With the help of virtual human models, the proposed framework can generate extensive synthetic facial datasets (e.g., head pose or face depths datasets) with a high degree of control over facial and environmental variations such as pose, illumination, and background. Such large datasets can be used for the improved and targeted training of deep neural networks., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Convolutional Neural Networks (CNN) have gained popularity as the de-facto model for any computer vision task. However, CNN have drawbacks, i.e. they fail to extract long-range perceptions in images. Due to their ability to capture long-range dependencies, transformer networks are adopted in computer vision applications, where they show state-of-the-art (SOTA) results in popular tasks like image classification, instance segmentation, and object detection. Although they gained ample attention, transformers have not been applied to 3D face reconstruction tasks. In this work, we propose a novel hierarchical transformer model, added to a feature pyramid aggregation structure, to extract the 3D face parameters from a single 2D image. More specifically, we use pre-trained Swin Transformer backbone networks in a hierarchical manner and add the feature fusion module to aggregate the features in multiple stages. We use a semi-supervised training approach and train our model in a supervised way with the 3DMM parameters from a publicly available dataset and unsupervised training with a differential renderer on other parameters like facial keypoints and facial features. We also train our network on a hybrid unsupervised loss and compare the results with other SOTA approaches. When evaluated across two public datasets on face reconstruction and dense 3D face alignment tasks, our method can achieve comparable results to the current SOTA performance and in some instances do better than the SOTA methods. A detailed subjective evaluation also shows that our method performs better than the previous works in realism and occlusion resistance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shubhajit Basak reports financial support was provided by Science Foundation Ireland. Funding details : Science Foundation Ireland Centre for Research Training in Digitally-Enhanced Reality (d-real) under Grant 18/CRT/6224, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Preoperative imaging of patients with endometriosis allows adequate counselling, referral to appropriate centres of expertise and workforce planning. The objective of this study was to assess the feasibility of simplified three-category preoperative endometriosis MRI morphological descriptors to predict subsequent surgical management., Methods: A single-centre observational study in 76 patients (median age 38 years, range 18-55) with preoperative endometriosis mapping MRI between 1 Jan 2015 and 31 Dec 2019. MRI studies were prospectively re-read blind-to-surgical outcome to categorise rectosigmoid morphology as normal, spider-shaped (linear T2-dark fibrotic bands) superficial endometriosis or typical crescentic or mushroom-shaped deep infiltrating endometriosis (DIE). Bowel motility was similarly categorised as normal, tethered or distorted/fixed. The reference standard was subsequent surgery within 3 years of MRI, categorised as no bowel surgery, adhesiolysis only or more complex surgeries., Results: Despite three-quarters of surgical cases having normal bowel morphology on preoperative MRI (72%, 55/76; 12% linear superficial endometriosis, 10% crescentic and 5% mushroom-shaped DIE) more than half showed bowel tethering (54%, 41/76) or distortion/fixation (10%, 8/76) and most patients underwent adhesiolysis (79%, 60/76). Complex surgery such as bowel resection, laparotomy conversion or complex adhesiolysis is predicted by morphology (crescentic or mushroom-shaped DIE, P < 0.001) and motility (tethered or distorted bowel, P = 0.002) descriptors., Conclusions: Comprehensive and clinically relevant diagnostic reporting does not have to be convoluted to have clinical impact: in our study population, categorising bowel morphology as normal, spider-shaped (superficial) or crescentic/mushroom-(DIE) shaped and motility as normal, tethered (superficial) or distorted/fixed (deep endometriosis) correlates to subsequent surgical complexity., (© 2022 The Royal Australian and New Zealand College of Radiologists.)

Introduction: Surgical excision of deep infiltrating endometriosis (DIE) is complex and associated with morbidity. Diagnostic imaging plays an important role in the preoperative workup. We sought to determine the utility of single sagittal T2-weighted MRI motion sequence in the preoperative assessment of pelvic mobility in patients with endometriosis., Methods: An observational study at a single tertiary public referral centre in Australia. Eighty-one MRI studies from 1 May 2019 to 3 December 2019, were enrolled. Studies were included if they were performed to stage endometriosis, including a T2-weighted motion series, adequately covering a uterus, cervix and rectum. Fifty-seven studies met inclusion criteria. The reference standard was a contemporaneous transvaginal ultrasound (TVUS) reporting on pelvic organ mobility. Three subspecialist radiologists were then blindly asked to identify, on the cine loop: rectouterine immobility, superficial endometriosis (pelvic bowel adhesions), rectosigmoid Deep Infiltrating Endometriosis (DIE). Fleiss' Kappa assessed interobserver agreement. Consensus MRI sensitivity and specificity were estimated against the reference standard (TVUS)., Results: Median age was 35 years (range 19-51). Forty-three cases had a contemporaneous TVUS; 14 reporting a sliding sign, 29 with fixed pelves. Interobserver agreement was 'substantial' (k = 0.79) for absent MRI sliding sign and 'almost perfect' (k = 0.90) for absence of DIE. Consensus MRI had 90% sensitivity (95% CI 73-98%) for pelvic immobility at TVUS (absent sliding sign). Interobserver agreement and consensus MRI sensitivity were higher for adhesions and immobility than normal findings., Conclusion: An MRI motion sequence can identify patients with pelvic adhesions and immobility, helping determine surgical difficulty when TVUS is not diagnostic., (© 2021 The Royal Australian and New Zealand College of Radiologists.)

Background: Caesarean scar ectopic pregnancy (CSP) is defined as blastocyst implantation occurring in a uterine scar. The incidence of CSP continues to rise with increasing caesarean section rates; prevalence is estimated to be 1:1800 to 1:2226 of all pregnancies. To date, over 30 treatment regimens have been published. The Royal College of Obstetricians and Gynaecologists guidelines (2016) state there is insufficient evidence to support one specific intervention over another., Aim: To review outcomes of medical and surgical management of CSP cases at a single tertiary centre over a nine-year period, in order to establish the safest and most effective management approach., Materials and Methods: An audit was undertaken of patients treated for CSP between January 2009 and March 2017 at King Edward Memorial Hospital, Western Australia. Patient demographic and treatment outcome data were extracted from medical records., Results: Fifty-one patients were identified as having CSP diagnosed during this time period, of which five were excluded due to lack of data, leaving a total of 46 cases. The majority of patients (52%, n = 24) elected for initial surgical management, while 41% (n = 19) trialled medical management. Seven percent (n = 3) opted for conservative management. Success rates of surgical, medical and conservative management were 100%, 53% and 0% respectively (P < 0.001). Medical management was associated with prolonged follow-up; there was no difference in complication rates between surgical and medical managements., Conclusions: In this audit, surgical management was the most effective way to manage CSP. There was no significant difference in complication rates between the two groups., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: Whether unintended discontinuation of common, evidence-based, long-term medication occurs after hospitalisation; what factors are associated with unintended discontinuation; and whether the presence of documentation of medication at hospital discharge is associated with continuity of medication in general practice., Design: Retrospective cohort study between 2012 and 2015., Setting: Electronic records and hospital supplied discharge notifications in 44 Irish general practices., Participants: 20 488 patients aged 65 years or more prescribed long-term medication for chronic conditions., Primary and Secondary Outcomes: Discontinuity of four evidence-based medication drug classes: antithrombotic, lipid-lowering, thyroid replacement drugs and respiratory inhalers in hospitalised versus non-hospitalised patients; patient and health system factors associated with discontinuity; impact of the presence of medication in the hospital discharge summary on continuity of medication in a patient's general practitioner (GP) prescribing record at 6 months follow-up., Results: In patients admitted to hospital, medication discontinuity ranged from 6%-11% in the 6 months posthospitalisation. Discontinuity of medication is significantly lower for hospitalised patients taking respiratory inhalers (adjusted OR (AOR) 0.63, 95% CI (0.49 to 0.80), p<0.001) and thyroid medications (AOR 0.62, 95% CI (0.40 to 0.96), p=0.03). There is no association between discontinuity of medication and hospitalisation for antithrombotics (AOR 0.95, 95% CI (0.81 to 1.11), p=0.49) or lipid lowering medications (AOR 0.92, 95% CI (0.78 to 1.08), p=0.29). Older patients and those who paid to see their GP were more likely to experience increased odds of discontinuity in all four medicine groups. Less than half (39% to 47.4%) of patients had medication listed on their hospital discharge summary. Presence of medication on hospital discharge summary is significantly associated with continuity of medication in the GP prescribing record for lipid lowering medications (AOR 1.64, 95% CI (1.15 to 2.36), p=0.01) and respiratory inhalers (AOR 2.97, 95% CI (1.68 to 5.25), p<0.01)., Conclusion: Discontinuity of evidence-based long-term medication is common. Increasing age and private medical care are independently associated with a higher risk of medication discontinuity. Hospitalisation is not associated with discontinuity but less than half of hospitalised patients have medication recorded on their hospital discharge summary., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We examined the relationship between timing and duration of folic acid (FA) supplementation in achieving red blood cell (RBC) folate levels in early pregnancy which are optimal (>906 nmol/l) for the prevention of neural tube defects (NTDs)., Methods: Clinical, FA supplementation and dietary folate details were computerized at the first antenatal visit. Maternal blood samples were analysed for RBC and serum folate., Results: Of the 502 women, 98.2% (n = 493) reported taking FA. There was a positive correlation between duration of supplementation and both RBC folate (r = 0.43, P < 0.001) and serum folate (rho = 0.29, P < 0.001). The optimal RBC folate level was achieved in 80.4% (n = 46) of women who started FA 400 μg 4-8 weeks before their LMP compared with only 53.6% (n = 153) in women who started 4-8 weeks after their LMP (P < 0.001)., Conclusions: This study provides, for the first time, information on both the timing and duration of FA that will achieve the optimum RBC folate levels associated with the prevention of NTDs. Women who are taking FA (400 μg) need to start before they conceive.

Background: Transitional care provides for the continuity of care as patients move between different stages and settings of care. Medication discrepancies arising at care transitions have been reported as prevalent and are linked with adverse drug events (ADEs) (e.g. rehospitalisation).Medication reconciliation is a process to prevent medication errors at transitions. Reconciliation involves building a complete list of a person's medications, checking them for accuracy, reconciling and documenting any changes. Despite reconciliation being recognised as a key aspect of patient safety, there remains a lack of consensus and evidence about the most effective methods of implementing reconciliation and calls have been made to strengthen the evidence base prior to widespread adoption., Objectives: To assess the effect of medication reconciliation on medication discrepancies, patient-related outcomes and healthcare utilisation in people receiving this intervention during care transitions compared to people not receiving medication reconciliation., Search Methods: We searched CENTRAL, MEDLINE, Embase, seven other databases and two trials registers on 18 January 2018 together with reference checking, citation searching, grey literature searches and contact with study authors to identify additional studies., Selection Criteria: We included only randomised trials. Eligible studies described interventions fulfilling the Institute for Healthcare Improvement definition of medication reconciliation aimed at all patients experiencing a transition of care as compared to standard care in that institution. Included studies had to report on medication discrepancies as an outcome., Data Collection and Analysis: Two review authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. Study-specific estimates were pooled, using a random-effects model to yield summary estimates of effect and 95% confidence intervals (CI). We used the GRADE approach to assess the overall certainty of evidence for each pooled outcome., Main Results: We identified 25 randomised trials involving 6995 participants. All studies were conducted in hospital or immediately related settings in eight countries. Twenty-three studies were provider orientated (pharmacist mediated) and two were structural (an electronic reconciliation tool and medical record changes). A pooled result of 20 studies comparing medication reconciliation interventions to standard care of participants with at least one medication discrepancy showed a risk ratio (RR) of 0.53 (95% CI 0.42 to 0.67; 4629 participants). The certainty of the evidence on this outcome was very low and therefore the effect of medication reconciliation to reduce discrepancies was uncertain. Similarly, reconciliation's effect on the number of reported discrepancies per participant was also uncertain (mean difference (MD) -1.18, 95% CI -2.58 to 0.23; 4 studies; 1963 participants), as well as its effect on the number of medication discrepancies per participant medication (RR 0.13, 95% CI 0.01 to 1.29; 2 studies; 3595 participants) as the certainty of the evidence for both outcomes was very low.Reconciliation may also have had little or no effect on preventable adverse drug events (PADEs) due to the very low certainty of the available evidence (RR 0.37. 95% CI 0.09 to 1.57; 3 studies; 1253 participants), with again uncertainty on its effect on ADE (RR 1.09, 95% CI 0.91 to 1.30; 4 studies; 1363 participants; low-certainty evidence). Evidence of the effect of the interventions on healthcare utilisation was conflicting; it probably made little or no difference on unplanned rehospitalisation when reported alone (RR 0.72, 95% CI 0.44 to 1.18; 5 studies; 1206 participants; moderate-certainty evidence), and had an uncertain effect on a composite measure of hospital utilisation (emergency department, rehospitalisation RR 0.78, 95% CI 0.50 to 1.22; 4 studies; 597 participants; very low-certainty evidence)., Authors' Conclusions: The impact of medication reconciliation interventions, in particular pharmacist-mediated interventions, on medication discrepancies is uncertain due to the certainty of the evidence being very low. There was also no certainty of the effect of the interventions on the secondary clinical outcomes of ADEs, PADEs and healthcare utilisation.

Objectives: Decision analysis study that incorporates patient preferences and probability estimates to investigate the impact of women's preferences for referral or an alternative strategy of watchful waiting if faced with symptoms that could be due to breast cancer., Setting: Community-based study., Participants: Asymptomatic women aged 30-60 years., Interventions: Participants were presented with 11 health scenarios that represent the possible consequences of symptomatic breast problems. Participants were asked the risk of death that they were willing to take in order to avoid the health scenario using the standard gamble utility method. This process was repeated for all 11 health scenarios. Formal decision analysis for the preferred individual decision was then estimated for each participant., Primary Outcome Measure: The preferred diagnostic strategy was either watchful waiting or referral to a breast clinic. Sensitivity analysis was used to examine how each varied according to changes in the probabilities of the health scenarios., Results: A total of 35 participants completed the interviews, with a median age 41 years (IQR 35-47 years). The majority of the study sample was employed (n=32, 91.4%), with a third-level (university) education (n=32, 91.4%) and with knowledge of someone with breast cancer (n=30, 85.7%). When individual preferences were accounted for, 25 (71.4%) patients preferred watchful waiting to referral for triple assessment as their preferred initial diagnostic strategy. Sensitivity analysis shows that referral for triple assessment becomes the dominant strategy at the upper probability estimate (18%) of breast cancer in the community., Conclusions: Watchful waiting is an acceptable strategy for most women who present to their general practitioner (GP) with breast symptoms. These findings suggest that current referral guidelines should take more explicit account of women's preferences in relation to their GPs initial management strategy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Surveillance of congenital anomalies is important to identify potential teratogens., Methods: This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models., Results: Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing., Conclusions: The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.

Virtual characters that appear almost photo-realistic have been shown to induce negative responses from viewers in traditional media, such as film and video games. This effect, described as the uncanny valley, is the reason why realism is often avoided when the aim is to create an appealing virtual character. In Virtual Reality, there have been few attempts to investigate this phenomenon and the implications of rendering virtual characters with high levels of realism on user enjoyment. In this paper, we conducted a large-scale experiment on over one thousand members of the public in order to gather information on how virtual characters are perceived in interactive virtual reality games. We were particularly interested in whether different render styles (realistic, cartoon, etc.) would directly influence appeal, or if a character's personality was the most important indicator of appeal. We used a number of perceptual metrics such as subjective ratings, proximity, and attribution bias in order to test our hypothesis. Our main result shows that affinity towards virtual characters is a complex interaction between the character's appearance and personality, and that realism is in fact a positive choice for virtual characters in virtual reality.

Neural tube defects (NTD) are potentially preventable in two-thirds of cases by periconceptional maternal Folic Acid (FA) supplementation. A national audit for the years 2009-11 showed no decline in NTD rates over twenty years. The aim of this national audit was to determine trends/rates and inform revision of national FA supplementation and food fortification strategies. Of 274,732 live and stillbirths there were 121(42.0%) cases of anencephaly, 136(47.2%) cases of spina bifida and 31(10.8%) cases of encephalocoele giving a total of 288 and overall rate of 1.05/1000 compared with 1.04/1000 in 2009-11(NS). In the 184 women where the information was available, only 29.9%(n=55) reported starting FA before pregnancy. The number of cases diagnosed antenatally was 91%(n=262) and 53%(n=154) were live-born. This audit confirms that over a generation, healthcare interventions have not succeeded in decreasing the number of pregnancies in Ireland complicated by NTD, and that revised strategies need to be developed and implemented.

The polycystic ovary syndrome is a common endocrine disorder that has profound implications for women throughout their reproductive years. A diagnosis of polycystic ovary syndrome is associated with reproductive challenges including a difficulty in conceiving as well as the pregnancy-related complications of miscarriage, hypertensive disorders, gestational diabetes and prematurity. Consequently, polycystic ovary syndrome has profound implications for women and their offspring with regard to reproductive function in the short term and in the longer term the risk of chronic illness and congenital anomalies, and health care resources should be directed accordingly to mitigate against these risks.

Background: Chromosomal trisomies are associated with advancing maternal age. In Ireland, information on the total prevalence and outcome of trisomy affected pregnancies is unavailable. This study aimed to ascertain more precise data on Trisomies 21, 18 and 13 in a large Irish region during the period 2011-2013., Methods: Multiple information sources were used in case finding, including a regional congenital anomaly register, all maternity and paediatric hospitals in the region and the regional Department of Clinical Genetics., Results: There were 394 trisomy cases from 80 894 total births, of which 289 were Trisomy 21, 75 were Trisomy 18 and 30 were Trisomy 13. The total prevalence rate was 48.9/10 000 births, 35.7, 9.3 and 3.7 for Trisomies 21, 18 and 13, respectively. Over 90% of Trisomies 18/13 and 47% of Trisomy 21 were diagnosed prenatally; 61% of Trisomy 21 cases and nearly 30% of Trisomies 18/13 were live births; 38% all trisomy affected pregnancies ended in a termination., Conclusions: This study provides precise data on the total prevalence and outcome of trisomy affected pregnancies in the East of Ireland. Total prevalence rates were higher than previously reported. Prenatal diagnosis had a significant impact on outcome. These data provide a better basis for planning of services for live-born children affected by trisomy., (© The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: In Ireland, as in many other healthcare systems, mental health service provision is being reconfigured with a move toward more care in the community, and particularly primary care. Recording and surveillance systems for mental health information and activities in primary care are needed for service planning and quality improvement., Aims: We describe the development and initial implementation of a software tool ('mental health finder') within a widely used primary care electronic medical record system (EMR) in Ireland to enable large-scale data collection on the epidemiology and management of mental health and substance use problems among patients attending general practice., Methods: In collaboration with the Irish Primary Care Research Network (IPCRN), we developed the 'Mental Health Finder' as a software plug-in to a commonly used primary care EMR system to facilitate data collection on mental health diagnoses and pharmacological treatments among patients. The finder searches for and identifies patients based on diagnostic coding and/or prescribed medicines. It was initially implemented among a convenience sample of six GP practices., Results: Prevalence of mental health and substance use problems across the six practices, as identified by the finder, was 9.4% (range 6.9-12.7%). 61.9% of identified patients were female; 25.8% were private patients. One-third (33.4%) of identified patients were prescribed more than one class of psychotropic medication. Of the patients identified by the finder, 89.9% were identifiable via prescribing data, 23.7% via diagnostic coding., Conclusions: The finder is a feasible and promising methodology for large-scale data collection on mental health problems in primary care.

Producing cartoon animations is a laborious task, and there is a distinct lack of automatic tools to help animators, particularly with creating facial animation. The proposed method uses real-time video-based motion tracking to generate facial motion as input and then matches it to existing hand-created animation curves. The synthesized animations can then be refined and polished by an animator, saving considerable time in overall production.

Objective: The aim of this study was to survey GPs and community pharmacists (CPs) in Ireland regarding current practices of medication management, specifically medication reconciliation, communication between health care providers and medication errors as patients transition in care., Methods: A national cross-sectional survey was distributed electronically to 2364 GPs, 311 GP Registrars and 2382 CPs. Multivariable associations comparing GPs to CPs were generated and content analysis of free text responses was undertaken., Results: There was an overall response rate of 17.7% (897 respondents-554 GPs/Registrars and 343 CPs). More than 90% of GPs and CPs were positive about the effects of medication reconciliation on medication safety and adherence. Sixty per cent of GPs reported having no formal system of medication reconciliation. Communication between GPs and CPs was identified as good/very good by >90% of GPs and CPs. The majority (>80%) of both groups could clearly recall prescribing errors, following a transition of care, they had witnessed in the previous 6 months. Free text content analysis corroborated the positive relationship between GPs and CPs, a frustration with secondary care communication, with many examples given of prescribing errors., Conclusions: While there is enthusiasm for the benefits of medication reconciliation there are limited formal structures in primary care to support it. Challenges in relation to systems that support inter-professional communication and reduce medication errors are features of the primary/secondary care transition. There is a need for an improved medication management system. Future research should focus on the identified barriers in implementing medication reconciliation and systems that can improve it., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks' gestation), and terminations of pregnancy for fetal anomaly (TOPFAs). The prevalence of associated anomalies was reported in live births. The prevalence of trisomy 18 and trisomy 13 were 4.8 (95%CI: 4.7-5.0) and 1.9 (95%CI: 1.8-2.0) per 10,000 total births. Seventy three percent of cases with trisomy 18 or trisomy 13 resulted in a TOPFA. Amongst 468 live born babies with trisomy 18, 80% (76-83%) had a cardiac anomaly, 21% (17-25%) had a nervous system anomaly, 8% (6-11%) had esophageal atresia and 10% (8-13%) had an orofacial cleft. Amongst 240 Live born babies with trisomy 13, 57% (51-64%) had a cardiac anomaly, 39% (33-46%) had a nervous system anomaly, 30% (24-36%) had an eye anomaly, 44% (37-50%) had polydactyly and 45% (39-52%) had an orofacial cleft. For babies with trisomy 18 boys were less likely to have a cardiac anomaly compared with girls (OR = 0.48 (0.30-0.77) and with trisomy 13 were less likely to have a nervous system anomaly [OR = 0.46 (0.27-0.77)]. Babies with trisomy 18 or trisomy 13 do have a high proportion of associated anomalies with the distribution of anomalies being different in boys and girls., (© 2015 Wiley Periodicals, Inc.)

Introduction: The use of Clinical Prediction Rules (CPRs) has been advocated as one way of implementing actionable evidence-based rules in clinical practice. The current highly manual nature of deriving CPRs makes them difficult to use and maintain. Addressing the known limitations of CPRs requires implementing more flexible and dynamic models of CPR development. We describe the application of Information and Communication Technology (ICT) to provide a platform for the derivation and dissemination of CPRs derived through analysis and continual learning from electronic patient data., Model Components: We propose a multistep maturity model for constructing electronic and computable CPRs (eCPRs). The model has six levels - from the lowest level of CPR maturity (literaturebased CPRs) to a fully electronic and computable service-oriented model of CPRs that are sensitive to specific demographic patient populations. We describe examples of implementations of the core model components - focusing on CPR representation, interoperability, electronic dissemination, CPR learning, and user interface requirements., Conclusion: The traditional focus on derivation and narrow validation of CPRs has severely limited their wider acceptance. The evolution and maturity model described here outlines a progression toward eCPRs consistent with the vision of a learning health system (LHS) - using central repositories of CPR knowledge, accessible open standards, and generalizable models to avoid repetition of previous work. This is useful for developing more ambitious strategies to address limitations of the traditional CPR development life cycle. The model described here is a starting point for promoting discussion about what a more dynamic CPR development process should look like.

Background: To establish the prevalence and patterns of prescribing to pregnant women in an Irish primary care setting., Methods: We reviewed electronic healthcare records routinely collected in primary care, of pregnant women attending nine Dublin-based General Practices affiliated to the Irish Primary Care Research Network (IPCRN) for antenatal care between January 2007 and October 2013 (n = 2,361 pregnancies)., Results: Excluding folic acid, 46.8% (n = 1,104) of pregnant women were prescribed at least one medication. Amoxicillin (11.1%, n = 263) and co-amoxiclav (8.0%, n = 190) were the most commonly prescribed medication followed by topical clotrimazole (4.9%, n = 117), salbutamol inhalers (4.1%, n = 96) and paracetamol (4.0%, n = 95). General Medical Services (GMS) patients were more likely to receive a prescription than private patients (OR 2.81; 95%CI (2.28, 3.47)). We applied the US FDA pregnancy-risk categories as a proxy measure of prescribing appropriateness, with FDA Category D and X medications considered inappropriate. FDA Category D drugs were prescribed in 5.9% (n = 140) of pregnancies. FDA Category X drugs were prescribed in 4.9% (n = 116) of pregnancies but after exclusion of oral contraceptives, progestogens, infertility treatments Category X medications were prescribed in 0.6% (n = 13) of pregnancies. After the initial antenatal consultation the prescribing prevalence of FDA Category D medications reduced to 4.7% (n = 110) and Category X to 3.1% (n = 72)., Conclusions: The overall prevalence of prescribing to pregnant women in our cohort is low compared to studies internationally, however similar levels of prescribing for FDA Category D and X were found. Following the initial antenatal consultation levels of prescribing of the FDA Category D and X medications reduced, however there is potential to further reduce their use in early pregnancy. The IPCRN database has provided valuable information on the current practice of antenatal prescribing within this pilot group of practices however it is limited by the absence of morbidity and pregnancy outcome data.

Background: Neural tube defects (NTDs) are associated with deficient maternal folic acid peri-conceptionally. In Ireland, there is no mandatory folic acid food fortification, partly due to declining NTD rates in recent years. The aim of this study was to ascertain the incident rate of NTD during the period 2009-11 and describe epidemiologically NTD in Ireland., Methods: Cases were ascertained through multiple sources, including three regional congenital anomaly registers, all maternity hospitals nationally and paediatric hospitals providing care for children with spina bifida in the Republic of Ireland during the period 2009-11., Results: From 225 998 total births, 236 NTDs were identified, giving an incidence of 1.04/1 000 births, increasing from 0.92/1 000 in 2009 to 1.17/1 000 in 2011. Of all cases, 45% (n = 106) had anencephaly, 49% (n = 115) had spina bifida and 6% (n = 15) had an encephalocoele; 78% (n = 184) were liveborn or stillborn and 22% (n = 52) were terminations abroad. Peri-conceptional folic acid supplement intake was 13.7% among the 52.5% (n = 124) of cases whose folic acid supplement intake was known., Conclusion: The incidence of NTDs in the Republic of Ireland appears to be increasing. Renewed public health interventions, including mandatory folic acid food fortification, must be considered to reduce the incidence of NTD., (© The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective : To describe the epidemiology of orofacial clefts in the east of Ireland. Design and Setting : A descriptive epidemiologic study on 851 cases of orofacial cleft identified over a 25-year period from 1984 to 2008 from more than 500,000 births. Results : There were 438 (51.5%) cases of cleft lip with or without cleft palate and 413 (48.5%) cases of cleft palate. The total birth prevalence was 16.0 per 10,000 births for all orofacial clefts, 8.2 for cleft lip with or without cleft palate, and 7.8 for cleft palate. Of all cases, 63.7% (542/851) occurred as isolated anomalies, 21.5% (183/851) were associated with multiple anomalies, and 14.8% (126/851) were associated with a syndrome or chromosomal anomaly. A significantly increasing trend over the 25-year period was observed for cleft lip with or without cleft palate associated with syndromes or chromosomal anomalies among mothers younger than 35 years but not in those older than 35 years. Conclusion : A slightly higher rate of orofacial clefts was observed in the east of Ireland than was observed in European and multinational studies during the study period, and there were higher rates of cleft palate. The rising trend in the proportion of mothers aged 35 years or older in Ireland is not contributing significantly to orofacial clefts associated with chromosomal syndromes.

Objective: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome., Design: Population-based prevalence study based on EUROCAT congenital anomaly registries., Setting: Eight European countries., Population: 14.8 million births 1990-2009; 2.89% multiple births., Methods: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases., Main Outcome Measures: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome., Statistical Analysis: Poisson and logistic regression stratified for maternal age, country and time., Results: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59])., Conclusions: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening., (© 2014 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Due to the ease with which particulate blends tend to segregate, blend uniformity and chemical composition are two critical control parameters in nearly all solids manufacturing industries. The prevailing wisdom has been that microwave sensors are not capable of or sensitive enough to measure the relative concentrations of components in a blend. Consequently, it is common to turn to near infrared sensing to determine material composition on-line. In this study, a novel microwave sensor was designed and utilized to determine, separately, the concentrations of different components in a blend of microcrystalline cellulose, acetaminophen, and water. This custom microwave sensor was shown to have comparable accuracy to a commercial NIR probe for both chemical composition and moisture content determination., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Ten per cent to 15% of couples have difficulty in conceiving. A proportion of these couples will ultimately require assisted reproduction. Prior to controlled ovarian hyperstimulation (COH) a baseline ultrasound is performed to detect the presence of ovarian cysts.Previous research has suggested that there is a relationship between the presence of an ovarian cyst prior to COH and poor outcome during IVF., Objectives: The aim of this review was to determine the effectiveness and safety of functional ovarian cyst aspiration prior to ovarian stimulation versus a conservative approach in women with an ovarian cyst who were undergoing IVF or ICSI., Search Methods: We searched the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov, Google Scholar and PubMed. The evidence was current to April 2014 and no language restrictions were applied., Selection Criteria: We included all randomised controlled trials (RCTs) comparing functional ovarian cyst aspiration versus conservative management of ovarian cysts that have been seen on transvaginal ultrasound (TVS) prior to COH for IVF or ICSI. Ovarian cysts were defined as simple, functional ovarian cysts > 20 mm in diameter. Oocyte donors and women undergoing donor oocyte cycles were excluded., Data Collection and Analysis: Study selection, data extraction and risk of bias assessments were conducted independently by two review authors. The primary outcome measures were live birth rate and adverse events. The overall quality of the evidence for each comparison was rated using GRADE methods., Main Results: Three studies were eligible for inclusion (n = 339), all of which used agonist protocols. Neither live birth rate nor adverse events were reported by any of the included studies. There was no conclusive evidence of a difference between the group who underwent ovarian cyst aspiration and the conservatively managed group in the clinical pregnancy rate (OR 1.40, 95% CI 0.67 to 2.94, 3 studies, 339 women, I(2) = 0%, low quality evidence). This suggested that if the clinical pregnancy rate in women with conservative management was assumed to be 5%, the chance following cyst aspiration would be between 4% and 14%. There was no evidence of a difference between the groups in the mean number of follicles recruited (0.55 follicles, 95% CI -0.48 to 1.59, 2 studies, 159 women, I(2) = 0%, low quality evidence) or mean number of oocytes collected (0.41 oocytes, 95% CI -0.04 to 0.85, 3 studies, 339 women, I(2) = 0%, low quality evidence). Findings for the cancellation rate (two studies) were inconsistent but neither study reported a benefit for the aspiration group. The main limitations of the evidence were imprecision, inconsistency, questionable applicability, and poor reporting of study methods., Authors' Conclusions: There is insufficient evidence to determine whether drainage of functional ovarian cysts prior to controlled ovarian hyperstimulation influences live birth rate, clinical pregnancy rate, number of follicles recruited, or oocytes collected in women with a functional ovarian cyst. The findings of this review do not provide supportive evidence for this approach, particularly in view of the requirement for anaesthesia, extra cost, psychological stress and risk of surgical complications.

Background: Potentially inappropriate prescribing (PIP) in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. The prevalence of PIP in Ireland is estimated at 36% with an associated expenditure of over €45 million in 2007. The aim of this paper is to describe the application of the Medical Research Council (MRC) framework to the development of an intervention to decrease PIP in Irish primary care., Methods: The MRC framework for the design and evaluation of complex interventions guided the development of the study intervention. In the development stage, literature was reviewed and combined with information obtained from experts in the field using a consensus based methodology and patient cases to define the main components of the intervention. In the pilot stage, five GPs tested the proposed intervention. Qualitative interviews were conducted with the GPs to inform the development and implementation of the intervention for the main randomised controlled trial., Results: The literature review identified PIP criteria for inclusion in the study and two initial intervention components - academic detailing and medicines review supported by therapeutic treatment algorithms. Through patient case studies and a focus group with a group of 8 GPs, these components were refined and a third component of the intervention identified - patient information leaflets. The intervention was tested in a pilot study. In total, eight medicine reviews were conducted across five GP practices. These reviews addressed ten instances of PIP, nine of which were addressed in the form of either a dose reduction or a discontinuation of a targeted medication. Qualitative interviews highlighted that GPs were receptive to the intervention but patient preference and time needed both to prepare for and conduct the medicines review, emerged as potential barriers. Findings from the pilot study allowed further refinement to produce the finalised intervention of academic detailing with a pharmacist, medicines review with web-based therapeutic treatment algorithms and tailored patient information leaflets., Conclusions: The MRC framework was used in the development of the OPTI-SCRIPT intervention to decrease the level of PIP in primary care in Ireland. Its application ensured that the intervention was developed using the best available evidence, was acceptable to GPs and feasible to deliver in the clinical setting. The effectiveness of this intervention is currently being tested in a pragmatic cluster randomised controlled trial., Trial Registration: Current controlled trials ISRCTN41694007.

Objective: To identify pregnancy-related risk factors for different manifestations of congenital anorectal malformations (ARMs)., Design: A population-based case-control study., Setting: Seventeen EUROCAT (European Surveillance of Congenital Anomalies) registries, 1980-2008., Population: The study population consisted of 1417 cases with ARM, including 648 cases of isolated ARM, 601 cases of ARM with additional congenital anomalies, and 168 cases of ARM-VACTERL (vertebral, anal, cardiac, tracheo-esophageal, renal, and limb defects), along with 13 371 controls with recognised syndromes or chromosomal abnormalities., Methods: Multiple logistic regression analyses were used to calculate adjusted odds ratios (ORs) for potential risk factors for ARM, such as fertility treatment, multiple pregnancy, primiparity, maternal illnesses during pregnancy, and pregnancy-related complications., Main Outcome Measures: Adjusted ORs for pregnancy-related risk factors for ARM., Results: The ARM cases were more likely to be firstborn than the controls (OR 1.6, 95% CI 1.4-1.8). Fertility treatment and being one of twins or triplets seemed to increase the risk of ARM in cases with additional congenital anomalies or VACTERL (ORs ranging from 1.6 to 2.5). Maternal fever during pregnancy and pre-eclampsia were only associated with ARM when additional congenital anomalies were present (OR 3.9, 95% CI 1.3-11.6; OR 3.4, 95% CI 1.6-7.1, respectively), whereas maternal epilepsy during pregnancy resulted in a five-fold elevated risk of all manifestations of ARM (OR 5.1, 95% CI 1.7-15.6)., Conclusions: This large European study identified maternal epilepsy, fertility treatment, multiple pregnancy, primiparity, pre-eclampsia, and maternal fever during pregnancy as potential risk factors primarily for complex manifestations of ARM with additional congenital anomalies and VACTERL., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Roller compaction is commonly used in the pharmaceutical and nutraceutical industries to increase and narrow the size distribution of a particulate material, making it easier to process. Both the moisture content of the material and the density of the roller compacted ribbon affect the uniformity and physical properties of the resultant granules. Without process analytical technologies, these parameters cannot be determined on-line or in real time. In this study, the more commonly used near-infrared (NIR) spectroscopy was compared and contrasted with microwave resonance for the determination of roller-compacted ribbons' envelope density and moisture content. Results indicate that microwave resonance can offer improved accuracy, robustness, and ease-of-use compared with NIR spectroscopy for these property measurements., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: To assess the public health consequences of the rise in multiple births with respect to congenital anomalies., Design: Descriptive epidemiological analysis of data from population-based congenital anomaly registries., Setting: Fourteen European countries., Population: A total of 5.4 million births 1984-2007, of which 3% were multiple births., Methods: Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly., Main Outcome Measures: Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases., Results: Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths., Conclusions: The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Background: Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care., Methods/design: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted., Discussion: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges., Trial Registration: Current controlled trials ISRCTN41694007.

Several [Fe(II)2(N-EtHPTB)(μ-O2X)](2+) complexes (1·O2X) have been synthesized, where N-EtHPTB is the anion of N,N,N'N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxy-1,3-diaminopropane and O2X is an oxyanion bridge. Crystal structures reveal five-coordinate (μ-alkoxo)diiron(II) cores. These diiron(II) complexes react with O2 at low temperatures in CH2Cl2 (-90 °C) to form blue-green O2 adducts that are best described as triply bridged (μ-η(1):η(1)-peroxo)diiron(III) species (2·O2X). With one exception, all 2·O2X intermediates convert irreversibly to doubly bridged, blue (μ-η(1):η(1)-peroxo)diiron(III) species (3·O2X). Where possible, 2·O2X and 3·O2X intermediates were characterized using resonance Raman spectroscopy, showing respective νO-O values of ∼850 and ∼900 cm(-1). How the steric and electronic properties of O2X affect conversion of 2·O2X to 3·O2X was examined. Stopped-flow analysis reveals that oxygenation kinetics of 1·O2X is unaffected by the nature of O2X, and for the first time, the benzoate analog of 2·O2X (2·O2CPh) is observed.

Background: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA., Methods: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population., Results: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35-2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code., Conclusions: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954-4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012., (Copyright © 2012 Wiley Periodicals, Inc.)

Successful environmental management is partly contingent on the effective recognition and communication of environmental health risks to the public. Yet risk perceptions are known to differ between experts and laypeople; laypeople often exhibit higher perceptions of risk in comparison to experts, particularly when these risks are associated with radiation, nuclear power, or nuclear waste. This paper consequently explores stakeholder risk perceptions associated with a mercury-contaminated chloralkali production facility in Kazakhstan. Using field observations and in-depth interviews conducted in the vicinity of the Pavlodar Chemical Plant, this work assesses the relevance of the substantial on-site mercury contamination to the health and livelihoods of the local population with the goal of informing remediation activity through a combination of quantitative and qualitative risk assessments. The findings of this research study cannot be broadly generalized to all the primary stakeholders of the site due to the small sample size; however, the indifference of the local population towards both the possibility of mercury-related health risks and the need for mitigation activity could pose a substantial barrier to successful site remediation and also suggests that a qualitative understanding of stakeholder risk perceptions could play an important role in striving towards sustainable, long-term environmental risk management., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284/297 (96%), had heard of folic acid, and 178/297 (60%) knew that it could prevent NTD. Most, 270/297 (91%) had taken it during their pregnancy, but only 107/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.