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Background: There is a wealth of evidence to suggest that the Borderline Personality Disorder (BPD, or similar Emotionally Unstable Personality Disorder, EUPD) construct is harmful. We provide a commentary on the ideas expressed in the May Debate issue, highlighting both concerns and alternatives. Method: We bring together lived experience, clinical, and research expertise. This commentary was written collaboratively drawing on all these sources of evidence. Results: We outline evidence that the BPD construct is invalid, harmful, not necessary for effective treatment and a potential block to the development and evaluation of alternatives. Conclusions: We ask readers to consider these concerns, perspectives, and ideas.

Background We convened a two-round, modified Delphi panel to identify and reach consensus on additional potential quality indicators (QIs) for nursing home residents with dementia. Methods The study team identified 12 potential QIs for nursing home dementia care and treatment of behavioral disturbances based on review of the literature. All proposed QIs were readily available in administrative claims data. Panelists rated each QI on importance, usefulness, and feasibility (a total of 36 items) using a 9-point Likert scale. Data were collected using an online survey platform and virtual group discussion. We defined consensus as ≥70% of the panelists responding within a three-point range surrounding the median. A QI achieved relevance on a domain (importance, usefulness, feasibility) when the panel reached consensus and a median rating of 7-9. Results The study had a 100% response rate for both survey rounds. Twenty-four items achieved consensus, with 15 reaching relevance with a median >7. Three QIs (percent of long-stay residents with dementia prescribed APs, percent with physical restraint use, and percent with a positive behavioral symptom score) reached consensus at the highest median score (9) for importance. Only 2 of the 12 proposed QIs reached relevance on all three domains: percent of long-stay residents with dementia prescribed antipsychotics (APs) and percent prescribed benzodiazepines. Conclusions Of the proposed QIs, our panel of dementia care experts only reached consensus on two QIs: measuring long-stay resident prescriptions of APs and benzodiazepines. Challenges remain in identifying QIs that meet threshold of all three areas and accurately reflect quality nursing home dementia care.

BackgroundCognitive deficits affect a significant proportion of patients with bipolar disorder (BD). Problems with sustained attention have been found independent of mood state and the causes are unclear. We aimed to investigate whether physical parameters such as activity levels, sleep, and body mass index (BMI) may be contributing factors.MethodsForty-six patients with BD and 42 controls completed a battery of neuropsychological tests and wore a triaxial accelerometer for 21 days which collected information on physical activity, sleep, and circadian rhythm. Ex-Gaussian analyses were used to characterise reaction time distributions. We used hierarchical regression analyses to examine whether physical activity, BMI, circadian rhythm, and sleep predicted variance in the performance of cognitive tasks.ResultsNeither physical activity, BMI, nor circadian rhythm predicted significant variance on any of the cognitive tasks. However, the presence of a sleep abnormality significantly predicted a higher intra-individual variability of the reaction time distributions on the Attention Network Task.ConclusionsThis study suggests that there is an association between sleep abnormalities and cognition in BD, with little or no relationship with physical activity, BMI, and circadian rhythm.

BackgroundAn original cohort study found that over half of the individuals detained under Section 136 (S136) of the Mental Health Act 1983 were discharged home after assessment, and nearly half were intoxicated.AimsTo investigate whether the cohort was followed up by psychiatric services, characterise those repeatedly detained and assess whether substance use was related to these outcomes.MethodData were retrospectively collected from the notes of 242 individuals, who presented after S136 detention to a place of safety over a 6-month period, and were followed up for 1 year.ResultsAfter 1 year, 48% were in secondary care. Those with psychosis were the most likely to be admitted. Diagnoses of personality disorder or substance use were associated with multiple detentions; however, few were in contact with secondary services.ConclusionsCrisis and long-term care pathways for these groups need to be developed to reduce repeated and unnecessary police detention.

Emerging per- and polyfluorinated compounds (PFAS) compounds are of increasing interest for environmental monitoring, one being hexafluoropropylene oxide-dimer acid (HFPO-DA), commonly referred to as GenX. The following review describes existing liquid chromatography-mass spectrometry (LC-MS) methods used to analyze HFPO-DA, including sample preparation and method sensitivity relative to other PFAS. Analytical challenges are also described, in particular the significant formation of in-source fragmentation, dimer and dimer adducts which detract from [M−H](−) signal. Lastly, detected levels of HFPO-DA in environmental and biological samples are compared across the limited number of available field exposure studies, which found several μg/L concentrations in water samples taken near fluorochemical plant discharges.

Analysis of the brominated flame retardant hexabromocyclododecane (HBCDD) is characterized by the separation of its three predominant diastereomers. This analysis is typically performed using rever ...

Use of high-resolution mass spectrometry (HRMS) Q-TOF systems is discussed in this chapter, focusing on the innovative approaches of atmospheric pressure gas chromatography (APGC) and ion mobility separations (IMSs). Because of wide ranges of chemical/physical properties, pesticide coverage on HRMS systems is improved by introducing atmospheric pressure ion sources suitable for both liquid chromatography (LC) and gas chromatography (GC) inlets. An atmospheric pressure source enables relatively rapid switching with minimal hardware change or loss of vacuum, in addition to offering less in-source fragmentation than traditional GC–electron ionization (EI). Additionally, as the use of nontargeted screening relies on comprehensive sample coverage (i.e., generalized sample preparation and full spectral acquisition), instrumental techniques that both increase peak capacity of an analysis and improve mass separations greatly enhance identification capabilities. The implementation of both APGC and IMS to pesticide analyses addresses these aforementioned considerations and more, and their history, development, theory, and practical use are described.

BACKGROUND Cognitive Bias Modification (CBM) procedures have been used to train individuals to interpret ambiguous information in a negative or benign direction and have provided evidence that negative biases causally contribute to emotional vulnerability. METHOD Here we present the development and validation of a new form of CBM designed to manipulate the cognitive errors known to characterize both depression and anxiety. Our manipulation was designed to modify the biased cognitions identified by Beck's cognitive error categories (e.g. arbitrary inference, overgeneralisation) and typically targeted during therapy. RESULTS In a later test of spontaneous inferences, unselected (Experiment 1) and vulnerable participants (Experiment 2) who had generated positive alternatives rather than errors perceived novel hypothetical events, their causes and outcomes in a non-distorted manner. These groups were also less vulnerable to two different types of emotional stressor (video clips; and an imagined social situation). Furthermore participants' interpretation of their own performance on a problem-solving task was improved by the manipulation, despite actual performance showing no significant change. CONCLUSIONS These findings demonstrate that Cognitive Error Modification can promote positive inferences, reduce vulnerability to stress and improve self-perceptions of performance.

We assessed whether intentions and expectations formed in a hypothetical physical activity situation are different from those formed in a real situation; and whether the intentions and expectations of participants who are hypothetically given a free pass to attend a fitness class to better match their behaviour if they are administered a corrective entreaty (CE), than if they are not. In two separate studies, undergraduate university students were randomised into three groups: (a) Hypothetical (H); (b) Hypothetical with CE (HE) and (c) Real (R), and were asked to rate their intention and expectation to use a fitness pass. As hypothesised, significantly more participants expected that they would use the free fitness pass in the H group compared to the R group in both studies. Significantly fewer participants in the HE condition expected to use their free pass compared to the H group in Study 2. Also, significantly more corresponding expectation-behaviour relationships were found in the HE and R groups compared to the H group in both studies. Administering a CE influenced expectations formed in a hypothetical situation making them more similar to expectations formed in a real situation, and increased the specificity of tests of correspondence between expectation and behaviour.

Podocytes (glomerular visceral epithelial cells) release vesicles into urine. Podocyte vesicle-enriched fractions from normal and pathological human urine samples were prepared for proteomic analysis. An immunoadsorption method was applied and enrichment of podocyte vesicles was assessed. We identified 76 unique proteins. One protein, serum paraoxonase/arylesterase 1 (PON-1), was newly identified in normal human urine sample. We confirmed this result and showed PON-1 expression in normal human kidney. These results demonstrated the potential for using the urine samples enriched in podocyte vesicles as a starting material in studies aimed at discovery of biomarkers for diseases.

Transgenic mice carrying human Amyloid Precursor Protein mutations present amyloid plaque deposition in the brain upon aging. In this study, we characterized the changes of cortex proteome and endogenous Apolipoprotein E in these mice. Differential analysis of two-dimensional electrophoresis images revealed spots altered upon aging, transgene addition and plaque deposition. Alpha-synuclein and cytochrome oxidase polypeptide Va were up-regulated in transgenic mice. Upon aging, expression of ATP synthase alpha, alpha enolase, UMP-CMP kinase, and dihydropyrimidinase like-2 protein was modified. These proteins and their modification probably play a role in the amyloid aggregate formation in these mice.

Following any form of brain insult, proteins are released from damaged tissues into the cerebrospinal fluid (CSF). This body fluid is therefore an ideal sample to use in the search for biomarkers of neurodegenerative disorders and brain damage. In this study, we used human post-mortem CSF as a model of massive brain injury and cell death for the identification of such protein markers. Pooled post-mortem CSF samples were analyzed using a protocol that combined immunoaffinity depletion of abundant CSF proteins, off-gel electrophoresis, SDS-PAGE and protein identification by LC-MS/MS. A total of 299 proteins were identified, of which 172 proteins were not previously described to be present in CSF. Of these 172 proteins, more than 75% have been described as intracellular proteins suggesting that they were released from damaged cells. Immunoblots of a number of proteins were performed on individual post-mortem CSF samples and confirmed elevated concentrations in post-mortem CSF compared to ante-mortem CSF. Interestingly, among the proteins specifically identified in the post-mortem CSF, several have been previously described as biochemical markers of brain damage.

Nucleoli are plurifunctional nuclear domains involved in the regulation of several major cellular processes such as ribosome biogenesis, the biogenesis of non-ribosomal ribonucleoprotein complexes, cell cycle, and cellular aging. Until recently, the protein content of nucleoli was poorly described. Several proteomic analyses have been undertaken to discover the molecular bases of the biological roles fulfilled by nucleoli. These studies have led to the identification of more than 700 proteins. Extensive bibliographic and bioinformatic analyses allowed the classification of the identified proteins into functional groups and suggested potential functions of 150 human proteins previously uncharacterized. The combination of improvements in mass spectrometry technologies, the characterization of protein complexes, and data mining will assist in furthering our understanding of the role of nucleoli in different physiological and pathological cell states.

Early diagnosis and immediate therapeutic interventions are crucial factors to reduce the damage extent and the risk of death. Currently, the diagnosis of stroke relies on neurological assessment of the patient and neuro-imaging techniques including computed tomography and/or magnetic resonance imaging scan. An early diagnostic marker of stroke, ideally capable to discriminate ischemic from hemorrhagic stroke would considerably improve patient acute management. Using surface-enhanced laser desorption/ionization (SELDI) technology, we aimed at finding new early diagnostic plasmatic markers of stroke. Strong anionic exchange (SAX) SELDI profiles of plasma samples from 21 stroke patients were compared to 21 samples from healthy controls. Seven peaks appeared to be differentially expressed with significant p values (p < 0.05). Proteins were stripped from the SAX chips, separated on a one-dimensional electrophoresis (1-DE) gel and stained using mass spectrometry (MS)-compatible silver staining. Following in-gel tryptic digestion, the peptides were analyzed by MS. Four candidate proteins were identified as apolipoprotein CI (ApoC-I), apolipoprotein CIII (ApoC-III), serum amyloid A (SAA), and antithrombin-III fragment (AT-III fragment). Assessment of ApoC-I and ApoC-III levels in plasma samples using a sandwich enzyme-linked immunosorbent assay (ELISA) allowed to distinguish between hemorrhagic (n = 15) and ischemic (n = 16) stroke (p < 0.001). To the best of our knowledge, ApoC-I and ApoC-III are the first reported plasmatic biomarkers capable to accurately distinguish between ischemic and hemorrhagic stroke in a small number of patients. It requires further investigation in a large cohort of patients.

The definite diagnosis of Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, relies upon neuropathological data usually obtained at autopsy. In living patients, the diagnosis, based on suggestive clinical features and EEG abnormalities, can be aided by the detection of altered levels of isoforms of the 14-3-3 protein in the cerebrospinal fluid (CSF). However, the validity of this test has been recently challenged and the search for other, more reliable biomarkers for CJD remains highly desirable. The present study describes the identification of a new potential surrogate marker in the CSF of CJD-affected patients. A preliminary study employing surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) technology highlighted a protein at 13.4 kDa in a small group (n = 8) of CJD-affected patients. Further analysis aimed at identifying this protein using cationic exchange chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed it to be cystatin C. Additional immunoblot assays confirmed that the level of cystatin C was significantly increased (p

BackgroundIndividual placement and support (IPS) has been repeatedly demonstrated to be the most effective form of mental health vocational rehabilitation. Its no-discharge policy plus fixed caseloads, however, makes it expensive to provide.AimsTo test whether introducing a time limit for IPS would significantly alter its clinical effectiveness and consequently its potential cost-effectiveness.MethodReferrals to an IPS service were randomly allocated to either standard IPS or to time-limited IPS (IPS-LITE). IPS-LITE participants were referred back to their mental health teams if still unemployed at 9 months or after 4 months employment support. The primary outcome at 18 months was working for 1 day. Secondary outcomes comprised other vocational measures plus clinical and social functioning. The differential rates of discharge were used to calculate a notional increased capacity and to model potential rates and costs of employment.ResultsA total of 123 patients were randomised and data were collected on 120 patients at 18 months. The two groups (IPS-LITE = 62 and IPS = 61) were well matched at baseline. Rates of employment were equal at 18 months (IPS-LITE = 24 (41%) and IPS = 27 (46%)) at which time 57 (97%) had been discharged from the IPS-LITE service and 16 (28%) from IPS. Only 11 patients (4 IPS-LITE and 7 IPS) obtained their first employment after 9 months. There were no significant differences in any other outcomes. IPS-LITE discharges generated a potential capacity increase of 46.5% compared to 12.7% in IPS which would translate into 35.8 returns to work in IPS-LITE compared to 30.6 in IPS over an 18-month period if the rates remained constant.ConclusionsIPS-LITE is equally effective to IPS and only minimal extra employment is gained by persisting beyond 9 months. If released capacity is utilised with similar outcomes, IPS-LITE results in an increase by 17% in numbers gaining employment within 18 months compared to IPS and will increase with prolonged follow-up. IPS-LITE may be more cost-effective and should be actively considered as an alternative within public services.

The purpose of this study was to determine the prospective risk of intrauterine fetal death (IUFD) at ≥34 weeks' gestation for monochorionic and dichorionic twins receiving intensive antenatal fetal surveillance. The secondary objective was to calculate the incidence of prematurity-related neonatal morbidity/mortality rates that have been stratified by gestational week and chorionicity.A retrospective cohort study of all twins at ≥34 weeks' gestation who were delivered at the Medical University of South Carolina (1987-2010) was performed. Twins were cared for in a longstanding Twin Clinic with standardized treatment and surveillance protocols and supervised by a consistent Maternal-Fetal Medicine specialist. Gestational age-specific fetal/neonatal mortality rates and composite neonatal morbidity rates were compared by chorionicity. A generalized linear mixed model was used to identify variables that were associated with increased composite neonatal morbidity.Among 768 twin gestations (601 dichorionic and 167 monochorionic), only 1 dichorionic IUFD occurred. The prospective risk of IUFD at ≥34 weeks' gestation was 0.17% for dichorionic twins and 0% for monochorionic twins. Composite neonatal morbidity decreased with each gestational week (P.0001). Morbidity was increased by white race, gestational diabetes mellitus, and elective indication for delivery. The nadir of composite neonatal morbidity occurred at 36/0-36/6 weeks' gestation for monochorionic twins and 37/0-37/6 weeks' gestation for dichorionic twins.Our data do not support concern for an increased risk of stillbirth in uncomplicated intensively monitored monochorionic twins at ≥34 weeks' gestation. However, our data do show significantly increased rates of neonatal morbidity in late preterm monochorionic twins that cannot be justified by a corresponding reduction in the risk of stillbirth. We believe that our data support delivery of uncomplicated monochorionic twins at 37 weeks' gestation.

A classroom of diverse learners with diverse language backgrounds can be a great challenge for a classroom teacher. English Language Learners (ELL) present a particular challenge to teachers as they represent such a wide range of academic abilities, English language abilities, and academic background. Constructivism is widely touted as an approach to probe for children’s level of understanding and the ways in which that understanding can be taken to higher level thinking. Constructivism is a way of learning and thinking. It is how students make sense of the material and how they can be taught most effectively. Constructivism as an educational theory holds that teachers should take into account what students know. Teachers then build on this knowledge and allow students to put their knowledge into practice. This paper will explore how the theory of constructivism may benefit ELL students in an inclusive classroom.

Images obtained from high-throughput mass spectrometry (MS) contain information that remains hidden when looking at a single spectrum at a time. Image processing of liquid chromatography-MS datasets can be extremely useful for quality control, experimental monitoring and knowledge extraction. The importance of imaging in differential analysis of proteomic experiments has already been established through two-dimensional gels and can now be foreseen with MS images. We present MSight, a new software designed to construct and manipulate MS images, as well as to facilitate their analysis and comparison.

A 72-year-old man presented to his primary care physician witha1-monthhistoryof a lowerextremityulceration. Initially, he had noted a discrete area of warmth and erythema on the pretibial aspect of his right leg that did not blanch with pressure. He denied any recent history of trauma or travel. The area of erythema on his leg enlarged over the followingweeksdespiteoralamoxicillinclavulanatetherapy. Hismedicalhistoryrevealedautoimmunehepatitis,forwhich he had been placed on an oral regimen of prednisone (40 mg/d)andazathioprine(50mg/d)4monthsearlier.A large reticulated area of ulceration on his right lower extremity, withareasof fullnecrosis,wasobservedonphysical examination. The border was well defined, erythematous, bluish, and violaceous (Figure1). The results of a vasculitis workup (ie, serologic tests for antinuclear antibody, rheumatoid factor, and cardiolipin antibody; a cryoglobulin screen; and a cryofibrinogen screen) were negative. A biopsy specimen was obtained (Figure 2). What is your diagnosis?

Only few biological markers are currently available for the routine diagnosis of brain damage-related disorders including cerebrovascular, dementia, and other neurodegenerative diseases. In this study, post-mortem cerebrospinal fluid samples were used as a model of massive brain insult to identify new markers potentially relevant for neurodegeneration. The protein pattern of this sample was compared to the one of cerebrospinal fluid from healthy subjects by two-dimensional gel electrophoresis. Using gel imaging, N-terminal microsequencing, mass spectrometry, and immunodetection techniques, we identified 13 differentially expressed proteins. Most of these proteins have been previously reported to be somehow associated with brain destruction or with the molecular mechanisms underlying certain neurodegenerative conditions. These data indicate that the identified proteins indeed represent potential biomarkers of brain damage. We recently showed that H-FABP, a protein highly homologous to E-FABP and A-FABP identified in this study, is a potential marker of Creutzfeldt-Jakob disease and stroke.

Protein identification using automated data-dependent tandem mass spectrometry (MS/MS) is now a standard procedure. However, in many cases data-dependent acquisition becomes redundant acquisition as many different peptides from the same protein are fragmented, whilst only a few are needed for unambiguous identification. To increase the quality of information but decrease the amount of information, a nonredundant MS (nrMS) strategy has been developed. With nrMS, data analysis is an integral part of the overall MS acquisition and analysis, and not an endpoint as typically performed. In this nrMS workflow a matrix assisted laser desorption/ionization-time of flight-time of flight (MALDI-TOF/TOF) instrument is used. MS and restricted MS/MS data are searched and identified proteins are used to generate an "exclusion list", after in silico digestion. Peptide fragmentation is then restricted to only the most intense ions not present in the exclusion list. This process is repeated until all peaks are accounted for or the sample is consumed. Compared to nanoLC-MS/MS, nrMS yielded similar results for the analysis of six pooled two-dimensional electrophoresis (2-DE) spots. In comparison to standard data-dependent MALDI-MS/MS for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel band analysis, nrMS dramatically increased the number of identified proteins. It was also found that this new workflow significantly increased sequence coverage by identifying unexpected peptides, which can result from post-translational modifications.

Hydrophobic proteins are difficult to analyze by two-dimensional electrophoresis (2-DE) because of their intrinsic tendency to self-aggregate during the first dimension (isoelectric focusing, IEF) or the equilibration steps. This aggregation renders their redissolution for the second dimension uncertain and results in the reduction of the number and intensity of protein spots, and in undesirable vertical and horizontal streaks across gels. Trifluoroethanol (TFE) is traditionally used at high concentration to solubilize peptides and proteins for NMR studies. Depending upon its concentration, TFE strongly affects the three-dimensional structure of proteins. We report here a phase separation system based on TFE/CHCl(3), which is able to extract a number of intrinsic membrane proteins. The addition of TFE in the in-gel sample rehydration buffer to improve membrane protein IEF separation is also presented. The procedure using urea, thiourea, and sulfobetaine as chaotropic agents was modified by the addition of TFE and removing of sulfobetaine at an optimized concentration in the solubilization medium used for the first dimension. When using membrane fractions isolated from Escherichia coli, the intensity and the number of spots detected from 2-DE gels that used TFE in the solubilization medium were significantly increased. The majority of the proteins identified using peptide mass fingerprinting and tandem mass spectrometry (MS/MS) were intrinsic membrane proteins, proteins of beta barrel structure or transmembrane proteins.

The study of protein interactions using mass spectrometry (MS) for identification of the components of purified protein complexes is leading to the description of increasingly valuable data on protein function. Commonly proteins in a given complex are identified via MS analysis of in-gel digests of gel electrophoretically separated proteins. In this study, we have evaluated the use of an approach employing the digest of the whole protein complex to identify directly the proteins present in a purification of the CD4 receptor complex. We used a cysteinyl affinity capture method to reduce the complexity of the peptide mixture that was obtained from the tryptic digest of the whole protein complex to the rather limited mixture of only cysteine-containing peptides. Here we report the use of this approach with MS for identification of the CD4 receptor complex components CD4 and p56lck, along with several other proteins present in the detergent-solubilized fractions from the purification. We have been able to identify these proteins using peptide sequence data obtained from cysteine-containing peptides. With appropriate control experiments, we have demonstrated the specific nature of the CD4-p56lck interaction. In contrast, the other proteins identified are shown to arise from nonspecific interactions during the affinity chromatography purification suggesting a possible loss of specific interactions during the chromatography procedure. We found that the complexity of the mixture was reduced such that only 10% of the peptides derived from tryptic digest of the identified proteins were detected. This represents only one-third of the cysteine-containing peptides, however, suggesting that this approach does not enable detection of all individual proteins.

Twelve college-age students who had either a low grade point average or visual perceptual problems were provided a program of sensory integration activities to determine whether sensory integration therapy would affect their academic performance. Selected reading tests were administered to establish a pre-test baseline. The students were then given a sequenced program of sensory integration activities designed to stimulate the vestibular system. After a 14-week period, reading tests were again administered. Test results indicate a statistically significant improvement in reading skills and support the use of sensory integration therapy for individuals with difficulty learning at the college level.