Parietal activity in episodic retrieval measured by fMRI and MEG

Understanding the functional role of the left lateral parietal cortex in episodic retrieval requires characterization of both spatial and temporal features of activity during memory tasks. In a recent study using magnetoencephalography (MEG), we described an early parietal response in a cued-recall task. This response began within 100 milliseconds (ms) of the retrieval cue and lasted less than 400 ms. Spatially, the effect reached significance in all three anatomically defined left lateral parietal subregions included in the study. Here we present a multimodal analysis of both hemodynamic and electrophysiologic responses in the same cued-recall paradigm. Functional MRI (fMRI) was used to more precisely reveal the portion of the parietal cortex with the greatest response. The MEG data set was then reanalyzed to show the early MEG time course of the region identified by fMRI. We found that the hemodynamic response is greatest within the intraparietal sulcus. Further, the MEG pattern in this region shows a strong response during the first 300 ms following the cue to retrieve. Finally, when individual-dipole MEG activity is analyzed for the left cortical surface over the early 300-millisecond time window, significant recall-related activity is limited to a relatively small portion of the left hemisphere that overlaps the region identified by fMRI in the intraparietal sulcus.     

Meta-analysis of clinical risk factors for suicide among people presenting to emergency departments and general hospitals with suicidal thoughts and behaviours

Background

Suicidal thoughts and behaviours (STB) are a common reason for presentation to emergency departments and general hospitals. A meta-analysis of the strength of clinical risk factors for subsequent suicide might aid understanding of suicidal behaviour and help suicide prevention.

Methods

We conducted a meta-analysis of cohort and controlled studies on clinical risk factors and later suicide among people presenting to emergency departments and general hospitals with STB. Data were extracted from papers meeting inclusion criteria, published in Medline, PsycINFO, and Embase between 1 January 1960 and 10 October 2022 using papers located with the search terms ((suicide*).m_titl AND (emergency* OR accident and emergency OR casualty OR general hospital OR toxicology service).mp) or were indexed in PubMed and had titles located with the search terms (suicide* OR self-harm OR self-harm OR self-injury OR self-injury OR self-poisoning OR self-poisoning OR overdose OR para-suicide OR parasuicide [title/abstract]) AND (Emergency department OR emergency room OR Casualty OR general hospital OR toxicology OR accident and emergency [all fields]). Data about the association between clinical risk factors and suicide extracted from three or more studies were included in a random-effects meta-analysis of the odds of later death by suicide. The study was registered in PROSPERO and conducted according to MOOSE and PRISMA guidelines.

Results

Seventy-five studies reported on 741,624 people, of which 19,649 died by suicide (2.65%). Male sex (odds ratio (OR) = 1.99) and age (OR = 2.01) were the most consistently reported risk factors. The strongest associations with subsequent death by suicide related to violent self-harm methods at the hospital presentation, including: unspecified violent method (OR = 4.97), any violent method (OR = 4.57) and the specific violent methods of drowning (OR = 4.32), hanging (OR = 4.26), and use of firearms (OR = 10.08). Patients categorised as higher risk using suicide prediction scales or any other method that combined risk factors had moderately increased odds of suicide (OR = 2.58). Younger age, Black and Hispanic ethnicity, overdose, a diagnosis of adjustment disorder, and the absence of any psychiatric diagnosis were protective against suicide.

Conclusions

Most risk factors for suicide among people who have presented with STB are not strongly associated with later suicide. The strongest risk factors relate to self-harm methods. In the absence of clear indicators of future suicide, all people presenting with suicidality warrant a thorough assessment of their needs, and further research is needed before we can meaningfully categorise people with STB according to suicide risk.     

Modeling of under-detection of cases in disease surveillance

PURPOSE: Accurate epidemiological surveillance of leprosy is a matter of international public health concern. It often suffers, however, from potential problems of under-registration of reported cases, particularly in poorer and more socially deprived areas. Such problems also apply in the surveillance of many other communicable or transmissible diseases. We develop a Bayesian model for small-area disease rates that allows for censoring of case detection in suspect districts and can therefore be used to estimate under-reporting of cases in a given study region. METHODS: Such methods are applied to leprosy incidence in a municipality of Pernambuco State in North Eastern Brazil, using a social deprivation indicator as the basis for considering data from certain districts to be censored. The time period we consider was immediately prior to an extension of the coverage and efficacy of the control program and model predictions concerning under reporting can therefore be compared with more reliable data subsequently collected from the same region. RESULTS: The proposed method produces informative estimates of under detection of leprosy cases in the defined study region and these estimates compare well, both in size and in geographical location, with the numbers of cases subsequently detected. CONCLUSIONS: As illustrated by the application discussed in this article, the proposed model provides a general tool that may be used in spatial epidemiological surveillance situations where the available data is suspected to contain significant under-registrations of cases in certain geographical areas.     

Targeting the PI3K/mTOR Axis, Alone and in Combination with Autophagy Blockade, for the Treatment of Malignant Peripheral Nerve Sheath Tumors

There is a critical need for efficacious therapeutic strategies to improve the outcome of patients afflicted by malignant peripheral nerve sheath tumors (MPNST). Multiple lines of evidence suggest a role for deregulated phosphoinositide 3-kinase (PI3K)/mTOR signaling in MPNST, making this axis an attractive target for therapeutic manipulation. On the basis of previous observations obtained from in vitro experimentation, here we aimed to assess the effects of PI3K/mTOR blockade on MPNST growth in vivo. The anti-MPNST impact of XL765, a dual PI3K/mTOR inhibitor currently being evaluated in human cancer clinical trials, was tested in two human MPNST xenograft models (STS26T and MPNST724) and an experimental model of pulmonary metastasis (STS26T). XL765 abrogated human MPNST local and metastatic growth in severe combined immunodeficient mice. Notably, this therapeutic approach failed to induce apoptosis in MPNST cells but rather resulted in marked productive autophagy. Importantly, genetic and pharmacologic autophagy blockade reversed apoptotic resistance and resulted in significant PI3K/mTOR inhibition-induced MPNST cell death. The addition of the autophagy inhibitor, chloroquine, to the therapeutic regimen of MPNST xenografts after pretreatment with XL765 resulted in superior antitumor effects as compared with either agent alone. Together, preclinical studies described here expand our previous findings and suggest that PI3K/mTOR inhibition alone and (most importantly) in combination with autophagy blockade may comprise a novel and efficacious therapy for patients harboring MPNST. Mol Cancer Ther; 11(8); 1758-69. ?2012 AACR.     

The effects of peripheral message cues on clinicians' judgments about clients' psychological status

This research examined the influence of peripheral message cues on clinicians' judgment about the psychological status of clients. The elaboration likelihood model (ELM) of social persuasion suggests that peripheral message cues are likely to exert a greater influence on clinicians' judgments when a client's presentation meets some, but not all, diagnostic criteria for a disorder (i.e., when the presentation is ambiguous). Within this theoretical framework, we examined the effects of a peripheral message cue (level of irrelevant detail in the client's presentation) and presentation ambiguity on clinicians' judgments of need for treatment, illness severity, and distress. Consistent with predictions based on the ELM, for both obsessive-compulsive disorder and post-traumatic stress disorder presentations, high levels of irrelevant detail exerted a greater influence on clinicians' judgments of clients' need for treatment when presentation ambiguity was high than when it was low.