Recent developments in plant-downy mildew interactions.

Downy mildews are obligate oomycete pathogens that attack a wide range of plants and can cause significant economic impacts on commercial crops and ornamental plants. Traditionally, downy mildew disease control relied on an integrated strategies, that incorporate cultural practices, deployment of resistant cultivars, crop rotation, application of contact and systemic pesticides, and biopesticides. Recent advances in genomics provided data that significantly advanced understanding of downy mildew evolution, taxonomy and classification. In addition, downy mildew genomics also revealed that these obligate oomycetes have reduced numbers of virulence factor genes in comparison to hemibiotrophic and necrotrophic oomycetes. However, downy mildews do deploy significant arrays of virulence proteins, including so-called RXLR proteins that promote virulence or are recognized as avirulence factors. Pathogenomics are being applied to downy mildew population studies to determine the genetic diversity within the downy mildew populations and manage disease by selection of appropriate varieties and management strategies. Genome editing technologies have been used to manipulate host disease susceptibility genes in different plants including grapevine and sweet basil and thereby provide new soucres of resistance genes against downy mildews. Previously, it has proved difficult to transform and manipulate downy mildews because of their obligate lifestyle. However, recent exploitation of RNA interference machinery through Host-Induced Gene Silencing (HIGS) and Spray-Induced Gene Silencing (SIGS) indicate that functional genomics in downy mildews is now possible. Altogether, these breakthrough technologies and attendant fundamental understanding will advance our ability to mitigate downy mildew diseases.

A SNP-based consensus genetic map for synteny-based trait targeting in faba bean (Vicia faba L.).

Faba bean (Vicia faba L.) is a globally important nitrogen-fixing legume, which is widely grown in a diverse range of environments. In this work, we mine and validate a set of 845 SNPs from the aligned transcriptomes of two contrasting inbred lines. Each V. faba SNP is assigned by BLAST analysis to a single Medicago orthologue. This set of syntenically anchored polymorphisms were then validated as individual KASP assays, classified according to their informativeness and performance on a panel of 37 inbred lines, and the best performing 757 markers used to genotype six mapping populations. The six resulting linkage maps were merged into a single consensus map on which 687 SNPs were placed on six linkage groups, each presumed to correspond to one of the six V. faba chromosomes. This sequence-based consensus map was used to explore synteny with the most closely related crop species, lentil and the most closely related fully sequenced genome, Medicago. Large tracts of uninterrupted colinearity were found between faba bean and Medicago, making it relatively straightforward to predict gene content and order in mapped genetic interval. As a demonstration of this, we mapped a flower colour gene to a 2-cM interval of Vf chromosome 2 which was highly colinear with Mt3. The obvious candidate gene from 78 gene models in the collinear Medicago chromosome segment was the previously characterized MtWD40-1 gene controlling anthocyanin production in Medicago and resequencing of the Vf orthologue showed a putative causative deletion of the entire 5' end of the gene.

Identification of Faba bean genetic loci associated with quantitative resistance to the fungus Botrytis fabae, causal agent of chocolate spot.

Introduction: Chocolate spot, caused by the ascomycete fungus Botrytis fabae, is a devastating foliar disease and a major constraint on the quality and yield of faba beans (Vicia faba). The use of fungicides is the primary strategy for controlling the disease. However, high levels of partial genetic resistance have been identified and can be exploited to mitigate the disease. Methods: The partially resistant V. faba cultivar Maris Bead and susceptible Egyptian accession ig70726 were crossed, and a genetic mapping population of 184 individuals was genotyped in the F2 generation and screened for resistance to B. fabae infection in the F3, F5, and F6 generations in a series of field experiments. A high-density linkage map of V. faba containing 3897 DArT markers spanning 1713.7 cM was constructed. Results: Multiple candidate quantitative trait loci (QTLs) in 11 separate regions of the V. faba genome were identified; some on chromosomes 2, 3, and 6 overlapped with loci previously linked to resistance to Ascochyta leaf and pod blight caused by the necrotrophic fungus Ascochyta fabae. A transcriptomics experiment was conducted at 18 h post-inoculation in seedlings of both parents of the mapping population, identifying several differentially expressed transcripts potentially involved in early stage defence against B. fabae, including cell-wall associated protein kinases, NLR genes, and genes involved in metabolism and response to reactive oxygen species. Discussion: This study identified several novel candidate QTLs in the V. faba genome that contribute to partial resistance to chocolate spot, but differences between growing seasons highlighted the importance of multi-year phenotyping experiments when searching for candidate QTLs for partial resistance.

Comparing standard medical care for nonepileptic seizures in Chile and the United States.

OBJECTIVE: We sought to compare the diagnostic and treatment practices for psychogenic nonepileptic seizures (PNES) in the United States (US) to Chile. METHODS: A survey on the diagnostic and treatment practices for PNES was administered to practicing clinicians in Chile. Results from 96 Chilean respondents were compared to results from 307 US clinicians. Type I error (alpha) was set to 0.005 for multiple comparisons. DIAGNOSIS: The diagnosis of PNES is made by inpatient video-EEG/LTM in 89% of the US respondents compared to 25% of the Chilean respondents (p<0.0001). The diagnosis of PNES is made by history and exam alone at twice the rate in Chile (38%) than in the US (16%; p<0.0001). TREATMENT: A higher proportion of the Chilean respondents (65%) endorsed psychopharmacotherapy as potentially beneficial compared to the US respondents (31%; p<0.0001). DISCUSSION: This cross-cultural multi-site survey reveals some differences in PNES evaluation and management between neurologists and other clinicians in the US and in Chile. Access to video EEG may improve PNES diagnosis and treatment.

Scarred survivors: gate keepers and gate openers to healthcare for migrants in vulnerable circumstances.

Background: The main barriers to 'vulnerable migrants' receiving good quality primary care are language and administration barriers. Little is known about the experiences of healthcare discrimination faced by migrants from different cultural groups. The aim was to explore vulnerable migrants' perspectives on primary healthcare in a UK city. Methods: Three focus groups and two semi-structured interviews were aided by interpreters. These were analysed against a pre-developed framework based on national standards of care for vulnerable migrants. Recruitment was facilitated via a community organisation. Results: In total, 13 participants took part, six women and seven men. There were five Arabic speakers, four Farsi speakers and four English speakers. Themes included access to primary care, mental health, use of interpreters, post-migration stressors and cultural competency. Conclusion: Vulnerable migrants perceived high levels of discrimination and reported the value of a respectful attitude from health professionals. Appointment booking systems and re-ordering medication are key areas where language barriers cause the most disruption to patient care. Medication-only treatment plans have limitations for mental distress for this population. Community-based therapies which manage post-migration stressors are likely to enhance recovery.

Evaluating clinical librarian services: a systematic review.

BACKGROUND: Previous systematic reviews have indicated limited evidence and poor quality evaluations of clinical librarian (CL) services. Rigorous evaluations should demonstrate the value of CL services, but guidance is needed before this can be achieved. OBJECTIVES: To undertake a systematic review which examines models of CL services, quality, methods and perspectives of clinical librarian service evaluations. METHODS: Systematic review methodology and synthesis of evidence, undertaken collaboratively by a group of 8 librarians to develop research and critical appraisal skills. RESULTS: There are four clear models of clinical library service provision. Clinical librarians are effective in saving health professionals time, providing relevant, useful information and high quality services. Clinical librarians have a positive effect on clinical decision making by contributing to better informed decisions, diagnosis and choice of drug or therapy. The quality of CL studies is improving, but more work is needed on reducing bias and providing evidence of specific impacts on patient care. The Critical Incident Technique as part of a mixed method approach appears to offer a useful approach to demonstrating impact. CONCLUSIONS: This systematic review provides practical guidance regarding the evaluation of CL services. It also provides updated evidence regarding the effectiveness and impact of CL services. The approach used was successful in developing research and critical appraisal skills in a group of librarians.

Telehealth: improving maternity services by modern technology.

Hypertension is considered one of the most common medical disorders causing complexities in pregnancy. It could be a newly developed pregnancy-induced hypertension (PIH) or a pre-existing hypertension developing into superimposed pre-eclamptic toxaemia. PIH affects approximately 10% of pregnancies and can have a serious impact on both maternal and fetal well-being; hence requires frequent monitoring and timely intervention. National Institute for Health and Care Excellence (NICE) guidelines recommends once or twice weekly monitoring of blood pressure for such patients. The required frequent monitoring comes with certain implications for patients and healthcare services. An average patient with PIH would need to see her healthcare provider once or twice a week until delivery and 6 weeks thereafter. This certainly increases pressure on limited National Health Service (NHS) resources. Home-based monitoring using Telehealth technology can represent a potential solution for achieving good-quality care for the patient without increasing the workload for healthcare providers. We used 'Florence', a text-based technology platform to support home monitoring. We tested its acceptability, feasibility and safety to replace face-to-face appointments for blood pressure monitoring in selected patients with PIH. We implemented our project in three progressive phases using a plan, do, study, act methodology. Florence, telehealth technology was used for blood pressure monitoring instead of face-to-face appointments, and the effect of this innovative technology on the services and the patient experience was studied and necessary modifications were made before progression into the next phase. We recruited 75 patients over 12 months through the progressive phases and replaced around 800 face-to-face appointments by remotely supervised monitoring sessions with Florence successfully, with improved care and patient satisfaction. We also achieved better compliance with the NICE guidelines for blood pressure monitoring in PIH. Our project concluded that Telehealth can be a potential solution for improving care in maternity services, with lesser burden on NHS resources.

Economic cost of congenital CMV in the UK.

OBJECTIVE: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital disability. It can disrupt neurodevelopment, causing lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed, for the first time, to estimate the annual economic burden of managing cCMV and its sequelae in the UK. DESIGN: The study collated available secondary data to develop a static cost model. SETTING: The model aimed to estimate costs of cCMV in the UK for the year 2016. PATIENTS: Individuals of all ages with cCMV. MAIN OUTCOME MEASURES: Direct (incurred by the public sector) and indirect (incurred personally or by society) costs associated with management of cCMV and its sequelae. RESULTS: The model estimated that the total cost of cCMV to the UK in 2016 was £732 million (lower and upper estimates were between £495 and £942 million). Approximately 40% of the costs were directly incurred by the public sector, with the remaining 60% being indirect costs, including lost productivity. Long-term impairments caused by the virus had a higher financial burden than the acute management of cCMV. CONCLUSIONS: The cost of cCMV is substantial, predominantly stemming from long-term impairments. Costs should be compared against investment in educational strategies and vaccine development programmes that aim to prevent virus transmission, as well as the value of introducing universal screening for cCMV to both increase detection of children who would benefit from treatment, and to build a more robust evidence base for future research.

Role of ultrasound scanning in community contraceptive and reproductive health clinics.

BACKGROUND: The role of ultrasound scanning (USS) in the community setting of contraception and reproductive health (CRH) has not yet been clearly established. Abacus Clinics use ultrasound scans prior to referral for abortion where gestation is uncertain and for location of an intrauterine device/intrauterine system (IUD/IUS). OBJECTIVE: To audit the indications for USS performed in Abacus Clinics and to determine a minimum acceptable number of annual scans for each clinician. METHODS: A retrospective review of case notes was performed for a period of 3 months. RESULTS: The majority of women (36; 64%) had a scan to determine gestation prior to referral for abortion. In 12 (21%) women the scan was performed for location of an IUD/IUS. Two (4%) women had a scan for both indications. Only six (11%) women did not comply with the indications listed above but all were related to gestation or IUD/IUS use. In 16 women the scan significantly influenced decision-making regarding referral to the appropriate abortion service provider. The number of scans performed by individual doctors varied between two and 12. CONCLUSIONS: The use of USS prevented unnecessary referrals to hospital and delays in clients' care. The number of scans each clinician performed was small and the indications for future USS were only slightly changed. The new special skills module in ultrasound developed by the Faculty of Sexual and Reproductive Healthcare(FSRH) (formerly the Faculty of Family Planning and Reproductive Health Care) aims to set new standards and should improve training.

Personality traits in psychogenic nonepileptic seizures (PNES) and psychogenic movement disorder (PMD): Neuroticism and perfectionism.

OBJECTIVE: Psychogenic movement disorder (PMD) and psychogenic nonepileptic seizures (PNES) are two subtypes of conversion disorder (CD). In this case-control study, we asked whether these subtypes varied as a function of personality and history of childhood abuse. METHODS: Fifty-nine patients with PMD from the Human Motor Control Section Clinic at the National Institutes of Health, 43 patients with PNES from the Rhode Island Hospital Neuropsychiatry and Behavioral Neurology Division, and 26 healthy volunteers (HC) received a battery of neurological, psychiatric and psychological assessments, including the NEO Personality Inventory Revised (NEO PI-R), the Childhood Trauma Questionnaire (CTQ), and the Traumatic Life Events Questionnaire (TLEQ). RESULTS: One-way ANOVA between the three groups indicated significant differences in overall domains of Neuroticism (p=0.001) and Conscientiousness (p=0.009): Patients with PNES reported significantly greater levels of Neuroticism (p=0.002) and lower levels of Conscientiousness (p=0.023) than patients with PMD. Levels of Neuroticism remained significantly higher in both PMD and PNES than HC following correction for multiple comparisons. Patients with PNES reported greater levels of depressive and anxiety symptoms, overall psychopathology, greater history of sexual abuse, greater levels of alexithymia, higher levels of dissociative symptoms, and an earlier age at which they experienced their most distressing traumatic event than patients with PMD. CONCLUSIONS: These findings suggest that personality traits, type of abuse and age of onset of trauma varies as a function of CD subtype. Patients with PNES rated greater Neuroticism and lower Conscientiousness than patients with PMD. These differing psychological profiles may inform differing treatment approaches such as psychological therapies for PNES and physiotherapy (with/without psychotherapy) for PMD.

Risk of pregnancy and external validity in clinical trials of emergency contraception.

OBJECTIVES: To compare women who enroll in emergency contraception (EC) trials to those who decline and to understand why eligible women decline to participate. METHODS: Data were collected from all women seeking EC (n = 5,787) at three clinics in the USA and UK during a period of nearly 1 year (from September 1997 to August 1998). The main outcome measures were pregnancy risk calculated by adjusted cycle day of ovulation. RESULTS: Enrolled and non-enrolled women had similar mean ages and similar mean cycle lengths. However, the enrolled and non-enrolled groups were different with respect to adjusted cycle day of unprotected sexual intercourse (UPSI), the regularity of their cycles, recent hormone use, breastfeeding, the number of other acts of UPSI they had engaged in during the same cycle, and their willingness to participate in the study. Expected pregnancy risk among enrolled patients was higher than among non-enrolled EC seekers (6.5% vs 5.0%, p<0.001, calculated using Dixon conception probabilities, and 5.4% vs 4.6%, p = 0.086, calculated using Trussell conception probabilities). Unwillingness to take part in the study was the most common reason women did not enrol in the trial. Otherwise-eligible women most often declined to enrol because they were concerned about the effectiveness of the trial regimen. CONCLUSIONS: Women in EC trials are likely to face higher pregnancy risk than the general population. Clinical trials might overestimate the number of pregnancies averted by treatment because the number of expected pregnancies in trial populations is not representative of the population of all EC seekers. This information could be useful in projecting the public health impact of expanded EC access.

Use of ulipristal acetate and levonorgestrel for emergency contraception: a follow-up study.

OBJECTIVES: Previously we showed that increasing the choice of emergency contraception (EC) guided by medical eligibility did not result in wholesale large-scale usage of ulipristal acetate (UPA). This further 12-month study aimed to answer three questions. (1) Does offering choice of EC lead to change in methods used? (2) Are women who choose UPA more likely than those who choose levonorgestrel (LNG) to continue using condoms for subsequent contraception or to decline any ongoing contraception? (3) Do more women choosing LNG 'quick start' hormonal contraception? METHODS: A retrospective study of EC episodes (1 April 2012 to 31 March 2013) by quarters. Among women offered all three methods of EC (49.1%) we noted the method chosen, and decisions on ongoing contraception among those choosing either LNG or UPA. Differences were tested for statistical significance. RESULTS: In 6110 episodes of EC, LNG was issued in 69.2%, UPA in 26.0%, and a copper intrauterine device (Cu-IUD) was fitted in 4.8%. Quarter by quarter, the data show a small decline in LNG use, suggesting plateauing by the last quarter, and a significant increase in UPA use between the first and the other three quarters (p<0.001). Use of the Cu-IUD remained static. The percentage of women offered three methods rose to 54.2%. In women offered full choice (3000; 49.1%) we saw a significant increase in choice of UPA, from 39.3% to 48.6% (p<0.001). Women who chose LNG were more likely to quick start (p=0.02) or be continuing contraception already used (p<0.001). Overall, those choosing UPA were more likely to use condoms (p<0.001) but were no more likely to decline ongoing contraception (p=0.13). CONCLUSIONS: There was a significant increase in women using UPA for EC compared with our previous study, particularly among those wishing to use condoms for continuing contraception. Women choosing LNG were more likely to quick start pills or to continue current hormonal contraception. Detailed attention to continuing contraception following EC may be an important factor in the prevention of unwanted pregnancy.

Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized controlled trial.

OBJECTIVE: Emergency contraceptives can prevent unintended pregnancy after unprotected intercourse. The best-studied regimen ("Yuzpe") consists of ordinary combined oral contraceptives containing levonorgestrel and ethinyl estradiol. Women traditionally take one dose within 72 hours after unprotected intercourse, and a second dose 12 hours later. Historically, half experience nausea and a fifth vomit. The purpose of this study was to determine whether 1). women could use combined oral contraceptives other than those containing levonorgestrel and 2). eliminating the second dose improves comfort and convenience. METHODS: Women presenting within 72 hours after unprotected intercourse were randomized to receive 1). standard two-dose Yuzpe, 2). a variant of Yuzpe substituting norethindrone for levonorgestrel, or 3). only the first dose of Yuzpe, followed 12 hours later by a placebo. RESULTS: Perfect-use failure rates were low in all groups and did not differ in a statistically significant way (standard Yuzpe 2.0% [n = 589], norethindrone-ethinyl estradiol 2.7% [n = 547], single dose of Yuzpe 2.9% [n = 546]). Typical-use failure rates were slightly higher but similarly did not differ significantly. Side effects were similar across groups, except that women taking the single dose reported half the vomiting. Taking the pills with food did not seem to reduce nausea or vomiting, and the pills were not more effective when started sooner after unprotected intercourse. CONCLUSION: Oral contraceptives containing norethindrone-ethinyl estradiol work approximately as well for emergency contraception as levonorgestrel-ethinyl estradiol formulations and should be offered when first-line therapies are not available.

Effect of hormonal emergency contraception on bleeding patterns.

Spotting following the use of emergency contraception is not unusual, nor is anxiety in women waiting to see if the treatment has worked. It is not known whether such spotting should bring worry or relief. We, therefore, wished to see if there was any correlation between bleeding pattern and treatment outcome. Using data from a large multicenter efficacy trial, we examined bleeding patterns post-emergency contraception. The earlier in the cycle the pills were taken, the more likely the next bleed was to be early and the less likely it was to be on time. There was no observable difference in spotting rates between women who got pregnant and those who did not. The occurrence of spotting did not influence whether the next period was lighter or heavier.

Side effects of the Yuzpe regimen of emergency contraception and two modifications.

We investigated side effects after the standard Yuzpe regimen or two modifications: substituting norethindrone as the progestin or eliminating the second dose. We also examined the impact of taking either dose with food. Nearly two thirds of women reported at least one side effect, the majority of which were mild or moderate. Women in our study experienced more side effects after the second dose than after the first. Taking the first dose within 1 h of a meal or snack was associated with increased nausea and vomiting; taking the second dose within 1 h of a meal or snack was associated with decreased nausea and vomiting. A targeted approach to prophylactic antiemetic use could reduce the number of women given these drugs, and the number who experience unnecessary side effects. The impact of counseling on side effects should be further evaluated.

Estimating the effectiveness of emergency contraceptive pills.

OBJECTIVE: We use new estimates of conception probabilities by cycle day of intercourse, where cycle day is measured with day 1 being the first day of bleeding in a cycle, to propose a new approach for estimating the effectiveness of emergency contraceptive pills (ECPs). We use this new approach to examine the absolute effectiveness and the cost-effectiveness of ECPs and whether ECPs are more effective the sooner after unprotected intercourse they are initiated. METHODS: Using the new set of conception probabilities, we employ data from two recent clinical trials of ECPs, one from the Population Council and the other from the World Health Organization (WHO), to examine the effectiveness of the combined ECP regimen. RESULTS: The expected pregnancy rate among typical users was 6.2% in the Population Council trial and 7.4% in the WHO trial based on conception probabilities by cycle day relative to the day of ovulation. Based on conception probabilities by cycle day relative to the first day of bleeding, the expected pregnancy rates dropped to 5.4% and 5.2%, respectively. The two trials yield conflicting evidence regarding whether effectiveness declines with treatment delay. CONCLUSIONS: Our results suggest that the absolute levels of effectiveness for the Yuzpe regimen of emergency contraception and the cost-effectiveness of this regimen have probably been overstated when based on conception probabilities by cycle day relative to day of ovulation.

Intrauterine device insertion-related complications: can they be predicted?

OBJECTIVE: To determine risk factors affecting the incidence of intrauterine device (IUD) insertion-related complications and failures and, in particular, whether postcoital IUD insertions have a higher incidence of complications than routine IUD insertions. DESIGN: Retrospective case notes analysis. PARTICIPANTS: The study examined 545 case notes of patients having IUD insertions at East Cheshire NHS Trust family planning clinics between 1 October 1997 and 31 December 2000. MAIN OUTCOME MEASURES: The incidence of complications at insertion, or up to 12 weeks after insertion, was determined and included failed insertion, cervical problems, syncope, bradycardia, convulsions, early perforation and early expulsion. Fourteen potential risk factors were examined to determine the effect on incidence of complications. RESULTS: Failed insertions were statistically more likely in women who had never previously had a vaginal delivery and also when a less experienced doctor performed the insertion. Nulliparous women were at statistically increased risk of cervical problems and bradycardia. Cervical problems at insertion also increased significantly with age. Patients who were amenorrhoeic at insertion were more likely to suffer an early IUD expulsion. CONCLUSIONS: Of the potential risk factors, nulliparity was the most important. IUD insertion failures and complications were no more common in postcoital than routine IUD insertions. In general, complications were unpredictable, indicating the need for constant vigilance and the inserting doctor being trained and prepared to deal with any complication arising.

Intrauterine device insertions: setting our standards.

OBJECTIVE: To determine if the documentation for intrauterine device (IUD) insertions was satisfactory and to agree minimum standards for practice. METHOD: A list was drawn up with minimum standards for documentation in the case notes. These were agreed at the clinical audit meeting. A retrospective analysis of case notes was done and a list completed for each IUD insertion. SETTING AND PARTICIPANTS: IUD fittings at all the Abacus clinics from 1 September 1999 to 31 October 1999. RESULTS: Of the 232 IUD insertions, the gold standard for documentation was met in 20%, however documentation of essential criteria was met 93% and all criteria 83% of the time. Each doctor received individual, confidential, comparative feedback. CONCLUSION: We were able to agree a minimum standard for documentation to enhance adequate counselling, safe insertion, communication with colleagues and risk management.