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A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
Sodium valproate and related preparations have recently undergone regulatory review following concern about effects on the unborn child and doctors' failure to communicate risk. The issues are wider. Valproate is overused in psychiatry based on the false perception that ‘ease’ of use equates to better safety than alternatives. Valproic acid can disrupt fundamental physiological processes, the consequences of which are poorly understood and little discussed in the psychiatric literature. Valproate may be useful in a small number of patients with bipolar disorder but current prescribing patterns are unjustified. Perception needs to change.
Declaration of interest
D.C.O. is psychiatric commissioner on the Commission on Human Medicines and a member of the European Medicines Agency's Scientific Advisory Group on Psychiatry. He chaired the European Medicines Agency's review of the psychiatric use of valproate in pregnancy and women of childbearing potential.
Sedentary behaviour can be associated with poor mental health, but it remains unclear whether all types of sedentary behaviour have equivalent detrimental effects.
To model the potential impact on depression of replacing passive with mentally active sedentary behaviours and with light and moderate-to-vigorous physical activity. An additional aim was to explore these relationships by self-report data and clinician diagnoses of depression.
In 1997, 43 863 Swedish adults were initially surveyed and their responses linked to patient registers until 2010. The isotemporal substitution method was used to model the potential impact on depression of replacing 30 min of passive sedentary behaviour with equivalent durations of mentally active sedentary behaviour, light physical activity or moderate-to-vigorous physical activity. Outcomes were self-reported depression symptoms (cross-sectional analyses) and clinician-diagnosed incident major depressive disorder (MDD) (prospective analyses).
Of 24 060 participants with complete data (mean age 49.2 years, s.d. 15.8, 66% female), 1526 (6.3%) reported depression symptoms at baseline. There were 416 (1.7%) incident cases of MDD during the 13-year follow-up. Modelled cross-sectionally, replacing 30 min/day of passive sedentary behaviour with 30 min/day of mentally active sedentary behaviour, light physical activity and moderate-to-vigorous activity reduced the odds of depression symptoms by 5% (odds ratio 0.95, 95% CI 0.94–0.97), 13% (odds ratio 0.87, 95% CI 0.76–1.00) and 19% (odds ratio 0.81, 95% CI 0.93–0.90), respectively. Modelled prospectively, substituting 30 min/day of passive with 30 min/day of mentally active sedentary behaviour reduced MDD risk by 5% (hazard ratio 0.95, 95% CI 0.91–0.99); no other prospective associations were statistically significant.
Substituting passive with mentally active sedentary behaviours, light activity or moderate-to-vigorous activity may reduce depression risk in adults.
Freshwater mussels (Mollusca: Unionidae) are filter feeders that are relatively immobile, widely distributed and are known to concentrate trace metals in their shells (1,2,3). These characteristics make them good candidates for monitoring metal pollution in lakes and rivers. Another characteristic of mussels that make them particularly attractive as pollution monitors is the fact the shell is deposited in distinctive, annual growth layers. The concentrations of metals in these shell layers may provide a history ol the metals present in the environment where the mussel was collected.
Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.
To examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability.
Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS).
The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54–1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3–9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6–50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97.
Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.
Findings as to whether individuals’ experiences of physical maltreatment from their parents in childhood predict their own perpetration of physical maltreatment toward their children in adulthood are mixed. Whether the maltreatment experienced is severe versus moderate or mild may relate to the strength of intergenerational associations. Furthermore, understanding of the roles of possible mediators (intervening mechanisms linking these behaviors) and moderators of the intervening mechanisms (factors associated with stronger or weaker mediated associations) is still relatively limited. These issues were examined in the present study. Mediating mechanisms based on a social learning model included antisocial behavior as assessed by criminal behaviors and substance use (alcohol and drug use), and the extent to which parental angry temperament moderated any indirect effects of antisocial behavior was also examined. To address these issues, data were used from Generations 2 and 3 of a prospective three-generational study, which is an extension of the Oregon Youth Study. Findings indicated modest intergenerational associations for severe physical maltreatment. There was a significant association of maltreatment history, particularly severe maltreatment with mothers’ and fathers’ delinquency. However, neither delinquency nor substance use showed significant mediational effects, and parental anger as a moderator of mediation did not reach significance.
The development of rational treatments for tardive dyskinesia has been held back by limitations to our understanding of its aetiology, which even now does not extend far beyond its association with centrally acting dopamine-blocking drugs. This article reviews briefly the major aetiological theories and addresses general management and specific treatment options. Primary prevention and early recognition remain the crucial management issues because, once the condition is established, there are no satisfactory treatments. The article considers two newly developed drugs, valbenazine and deutetrabenazine, in some detail as, although they are not yet licensed in Europe, they have largely been responsible for an upsurge in interest in tardive dyskinesia in the North American literature and are likely to be widely promoted in the future. Although possessed of undoubted benefits, the evidence suggests that these represent small steps rather than large leaps forward in treatment.
•Be able to discuss the major aetiological theories on the causation of a common, and sometimes serious, adverse action of antidopaminergic drugs
•Understand general management and specific treatment options
•Understand the pharmacology and efficacy of two drugs recently approved by the FDA for the treatment of tardive dyskinesia
DECLARATION OF INTEREST
D.C.O. is psychiatric commissioner on the Commission on Human Medicines, the UK drug regulator, and chair of its expert advisory group on CNS drugs. He is also a member of the psychiatry Scientific Advisory Group of the European Medicines Agency.
Tardive dyskinesia is a common iatrogenic neurological and neurobehavioural syndrome associated with the use of antidopaminergic medication, especially antipsychotics. Prior to the introduction of the newer antipsychotics in the 1990s, it was one of the major areas of psychiatric research but interest waned as the new drugs were reputed to have a reduced liability to extrapyramidal adverse effects in general, a claim now discredited by numerous pragmatic research studies. Early small-scale short-term prevalence studies were presented as evidence to support the assumption that patients on the newer drugs did indeed have a lower prevalence of tardive dyskinesia but recent large-scale review of studies with patients exposed for longer suggest that things have not changed. This article presents a clinical overview of a complex and varied syndrome in terms of its phenomenology, epidemiology and risk factors; a companion article will consider treatment. This overview aims to highlight tardive dyskinesia once again, especially to practitioners who have trained in an environment where this was considered mainly in historical terms.
•Understand the complex phenomenology comprising the syndrome of tardive dyskinesia
•Appreciate recent data on prevalence and incidence with the newer antipsychotics
•Be aware of risk factors when recommending antipsychotic (and other antidopaminergic) drugs
The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored.
To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology.
Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic.
Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account.
Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits.