This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Background: Eptinezumab is approved in the US for the preventive treatment of migraine and was well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine (CM). The PREVAIL study evaluated the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with CM. Methods: PREVAIL was an open-label, phase 3 trial comprising two 48-week treatment phases. Adults with CM received eptinezumab 300 mg by 30-minute IV every 12 weeks for ≤8 doses, with patients followed up to week 104. Results: 128 adults (mean age, 41.5y) with CM were treated. Over 2 years, the most frequently reported treatment-emergent adverse events were nasopharyngitis (14.1%), upper respiratory tract infection (7.8%), sinusitis (7.8%), influenza (6.3%), bronchitis (5.5%), and migraine (5.5%). Study-drug discontinuation due to adverse events was 6.3%. Anti-eptinezumab antibody incidence peaked at week 24 and declined despite continued dosing, to nondetectable levels at week 104. Patient-reported outcomes were improved at first assessment (week 4) and generally sustained through week 104. Conclusions: In adults with CM, eptinezumab 300 mg demonstrated a favorable safety profile, limited long-term immunogenicity, early and sustained reductions in migraine-related burden, and improvements in health-related quality of life over 2 years.

Age at sexual debut is known to have implications for future sexual behaviours and health outcomes, including HIV infection, early pregnancy and maternal mortality, but may also influence educational outcomes. Longitudinal data on schooling and sexual behaviour from a demographic surveillance site in Karonga district, northern Malawi, were analysed for 3153 respondents between the ages of 12 and 25 years to examine the association between sexual debut and primary school dropout, and the role of prior school performance. Time to dropout was modelled using the Fine and Gray survival model to account for the competing event of primary school completion. To deal with the time-varying nature of age at sexual debut and school performance, models were fitted using landmark analyses. Sexual debut was found to be associated with a five-fold increase in rate of subsequent dropout for girls and a two-fold increase in dropout rate for boys (adjusted hazard ratio [aHR] of 5.27, CI 4.22–6.57, and 2.19, CI 1.77–2.7, respectively). For girls who were sexually active by age 16, only 16% ultimately completed primary schooling, compared with 70% aged 18 or older at sexual debut. Prior to sexual debut, girls had primary completion levels similar to those of boys. The association between sexual debut and school dropout could not be explained by prior poor school performance: the effect of sexual debut on dropout was as strong among those who were not behind in school as among those who were overage for their school grade. Girls who were sexually active were more likely to repeat a grade, with no effect being seen for boys. Pathways to dropout are complex and may differ for boys and girls. Interventions are needed to improve school progression so children complete primary school before sexual debut, and to improve sex education and contraception provision.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Titanomaghemite occurs in a relatively fresh doleritic intrusion in an area of Precambrian gneiss in Minas Gerais, Brazil. It hosts exsolution lamellae of ilmenite and contains more than 90% of the iron in the ferric form. It is more resistant to weathering than the ilmenite and is inherited virtually unaltered by the resulting soils. Titanomaghemite, extracted as grains from a weathered rind of the rock, has lattice parameter a0 = 0.8348(3) nm and has a canted spin structure due to substitution of non-magnetic ions on tetrahedral and octahedral sites of the spinel structure. The average canting angle is 32 ± 3° and canting occurs predominantly on the octahedral iron sublattice. Its formula, based on microprobe analysis and Mössbauer spectroscopy may be expressed as:

where [] and {} denote ions on tetrahedral and octahedral sites, respectively. The spontaneous magnetization of the mineral is 36(3) J/T/kg.

Field and column experiments were conducted to determine the effect of controlled release formulations on weed control and leaching of alachlor and metribuzin on a Plainfield sand. Controlled release formulations including two starch encapsulations of both herbicides and a microencapsulation of alachlor were compared to emulsifiable concentrate and dry flowable formulations of alachlor and metribuzin, respectively. Herbicide movement was measured in laboratory columns and in the field throughout two growing seasons to a soil depth of 91 cm. Soybean injury and weed control were monitored. No significant differences in herbicide movement between starch-encapsulated and emulsifiable concentrate formulations were observed in either field or column experiments. Microencapsulation resulted in the greatest retention of alachlor in the soil surface in field and columns. Compared to the dry flowable formulation, starch encapsulation did not affect metribuzin distribution in the field but reduced leaching in columns. Controlled release formulations did not result in significant differences in weed control and soybean injury compared to the emulsifiable concentrate alachlor and dry flowable metribuzin formulations. Starch encapsulations had a limited effect on alachlor and metribuzin movement. Degradation appeared to be the primary mechanism for herbicide dissipation while leaching losses were minor.

A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.

A 3-yr study was conducted on nine farms across southern Ontario to evaluate the risks and benefits of different approaches to weed management in corn and soybean. Weed control decisions were based on field scouting and recommendations from the Ontario version of HADSS™, the herbicide application decision support system. Treatments were selected to maximize profit (economic threshold approach) or to maximize yield (highest treatment efficacy). Reduced rates of the high efficacy treatment for each field also were included. Weed density before and after treatment, crop yields, weed seed return, and the effect of weed control decisions on weed density 1 yr after treatment were assessed. Crop yield varied among years and farms but was not affected by weed control treatment. Weed control at 28 d after treatment (DAT) was often lower and weed density, biomass, and seed production 70 DAT were often higher with the profit maximization approach compared with the yield maximization approach. However, weed density 1 yr later, after each cooperator had applied a general weed control program, did not vary significantly among the previous year's weed control treatments. Reduced rates of the high efficacy treatments did not lead to increased weed problems the next year, despite lower weed control and increased weed seed production in some years. During the 3 yr of the study, weed control costs with the profit maximization approach were approximately Can$45/ha less than with the yield maximization approach.

In 1997, farmers in Ontario, Canada, reported failure of some ALS-inhibiting herbicides to provide adequate control of pigweed species. Growth room experiments were conducted to confirm resistance to ALS inhibitors in populations of Powell amaranth and redroot pigweed. Twenty-two out of 35 collected seed samples were able to grow in the presence of soil-applied imazethapyr or flumetsulam. Dose–response curves were generated for 11 and 9 populations of Powell amaranth and redroot pigweed, respectively, using foliar-applied imazethapyr and thifensulfuron. Resistance to ALS inhibitors was confirmed in nine and five populations of Powell amaranth and redroot pigweed, respectively. Within each species, comparison of the herbicide rate required to reduce plant dry weight 50% (GR50) between the resistant populations and a susceptible population was conducted to obtain resistance factors. For imazethapyr, resistance factors ranged from 4.2 to 3,438 and from 33 to 168 for Powell amaranth and redroot pigweed, respectively. High-level cross-resistance to thifensulfuron was found in two populations of each species, with resistance factors ranging from 270 to 2,416. In both species, populations could be grouped according to their cross-resistance patterns: some populations were resistant to imazethapyr only, whereas others expressed resistance to both imazethapyr and thifensulfuron. The observed patterns of cross-resistance were not correlated with known herbicide exposure history of the fields where these populations originated.

Field experiments were conducted in 1998, 1999, and 2000 at two locations (Harrow and Ridgetown) in southwestern Ontario to determine the biologically effective rates (I90) of a commercial formulation of flufenacet plus metribuzin for weed control and processing tomato tolerance. At the proposed label use rate, flufenacet plus metribuzin provided excellent (≥90%) early-season (22 to 29 d after planting) control of velvetleaf, good (80 to 89%) control of barnyardgrass and redroot pigweed, and fair (60 to 79%) control of common lambsquarters. Flufenacet plus metribuzin provided fair late-season (59 to 97 d after planting) control of redroot pigweed and common lambsquarters and poor (≤59%) control of barnyardgrass and velvetleaf. At Harrow and Ridgetown, I90 values for early-season weed control ranged from 70 to 1,300 g ai/ha and 50 to 1,900 g ai/ha, respectively. Flufenacet plus metribuzin provided poor weed control at Ridgetown. This result was not attributable to higher weed density or particular weed species but may have been caused by lack of rainfall and too low application rates for the medium-textured soil type. It is estimated that flufenacet plus metribuzin at 1,400 g/ha can control green foxtail season-long, whereas barnyardgrass and common lambsquarters would require 1,900 g/ha. Season-long control of velvetleaf and redroot pigweed would require application rates of 3,200 and 7,100 g/ha, respectively. Only slight early-season crop injury was observed, which was not reflected in yields. Optimum yields of tomatoes were obtained at Harrow at rates lower or slightly higher than the registered rates for corn and soybean. Tomato yields were higher at Harrow than at Ridgetown, which may have been due to differences in soil texture. Tomatoes grown in a medium-textured (Ridgetown) soil appeared to be less competitive against weeds than those grown in a coarse-textured soil (Harrow).

Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.

Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial–constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.

We investigated offspring quality in fleas (Xenopsylla ramesis) feeding on non-reproducing, pregnant or lactating rodents (Meriones crassus) and asked whether (a) quality of flea offspring differs dependent on host reproductive status; (b) fleas trade off offspring quantity for quality; and (c) quality variables are inter-correlated. Emergence success was highest when parents exploited pregnant hosts, while development time was longest when parents exploited lactating hosts. Male offspring from fleas fed on non-reproductive and pregnant hosts were larger than those from lactating hosts whereas female offspring from fleas fed on pregnant hosts were larger than those from both lactating and non-reproductive hosts. Male offspring survived under starvation the longest when their parents exploited lactating hosts and the shortest when their parents exploited pregnant hosts. Female offspring of parents that exploited lactating hosts survived under starvation longer than those that exploited non-reproductive and pregnant hosts. Emergence success and development time decreased as mean number of eggs laid by mothers increased. Fleas that were larger and took longer to develop lived significantly longer under starvation. These results indicate the presence of a trade-off between offspring quantity and quality in fleas exploiting female Sundevall's jird in varying reproductive condition but this trade-off depended on the quality trait considered.

Two community-based density case-control studies were performed to assess risk factors for cholera transmission during inter-peak periods of the ongoing epidemic in two Haitian urban settings, Gonaives and Carrefour. The strongest associations were: close contact with cholera patients (sharing latrines, visiting cholera patients, helping someone with diarrhoea), eating food from street vendors and washing dishes with untreated water. Protective factors were: drinking chlorinated water, receiving prevention messages via television, church or training sessions, and high household socioeconomic level. These findings suggest that, in addition to contaminated water, factors related to direct and indirect inter-human contact play an important role in cholera transmission during inter-peak periods. In order to reduce cholera transmission in Haiti intensive preventive measures such as hygiene promotion and awareness campaigns should be implemented during inter-peak lulls, when prevention activities are typically scaled back.