Measuring sarcopenia on pre-operative CT in older adults undergoing emergency laparotomy: a comparison of three different calculations.

INTRODUCTION: Sarcopenia is associated with outcomes in older-adults undergoing emergency surgery. Psoas major measurement is a surrogate marker of sarcopenia with multiple calculations existing normalising to body size and no consensus as to which is optimal. We compared three different psoas-major calculations to predict outcomes in older adults undergoing emergency laparotomy. METHODS: Consecutive over 65s were identified from the National Emergency Laparotomy Audit(NELA) database at a single centre between 2014 and 2018. Psoas major was measured at the L3 level and normalised to height (psoas muscle index, PMI), L3 vertebral body (psoas muscle:L3 ratio, PML3) or body surface area (psoas:body surface area, PBSA) and each correlated to outcomes. Outcome measures included inpatient, 30-day and 90-day mortality. A comparison of the three calculations was performed using the Mann-Whitney U, chi-squared, receiver operating characteristic curves (ROC) and binary logistic regression. RESULTS: Two hundred and sixty-four older adults underwent emergency laparotomy (median age, 75 years ((IQR, 70-81 years), 50% female)). Inpatient mortality was 19.6%, 30-day mortality was 15.1% and 90-day mortality was 18.5%. A total of 31.1% of males and 30% of females were sarcopenic (30.6% overall). A multivariate analysis confirmed each method of psoas major calculation (p < 0.0001) to be associated with mortality, as was ASA-grade (p < 0.0001). Area under the curve (AUC) was greatest for PML3 in predicting mortality (inpatient: PML3, 0.76; PMI, 0.71; PBSA, 0.70; 30-day: PML3, 0.74; PMI, 0.68; PBSA, 0.68; and 90-day: PML3, 0.78; PMI, 0.71; PBSA, 0.70). ASA-grade, P-POSSUM and PML3 were independently associated with mortality on multivariate analysis. ROC analysis of predictions from logistic regression models demonstrated PML3 to be more closely aligned to mortality than ASA or P-POSSUM (inpatient: AUC:PML3, 0.807; ASA, 0.783; P-POSSUM, 0.762; 30-day:AUC: PML3, 0.799; ASA, 0.784; P-POSSUM, 0.787; and 90-day: AUC:PML3, 0.805; ASA, 0.781; P-POSSUM, 0.756). CONCLUSIONS: Sarcopenia was present in 30.6% of older adults undergoing emergency surgery and is associated with a significantly increased mortality. PML3 is superior to PMI or PBSA and should be considered the method of calculation of choice. Additionally, PML3 compares favourably to ASA and P-POSSUM.

Documenting the absence of brucellosis in cattle, goats and dogs in a "One Health" interface in the Mnisi community, Limpopo, South Africa.

This study shows the absence of the world's most common bacterial zoonoses caused by Brucella abortus and Brucella melitensis in cattle, goats and dogs in an agro-pastoral community in South Africa, where heifer vaccination against brucellosis with the live Strain 19 vaccine is compulsory. The study site is bordering wildlife reserves with multiple wildlife species infected with brucellosis. The results showed a low seroprevalence (1.4%) in cattle. Seroprevalence in cattle decreased with age after 4 years in females, males were less positive than females and a tissue culture from a brucellin skin test-positive male was negative. The results indicate that Brucella seropositivity in cattle is due to S19 vaccination and not natural infections. This conclusion is reinforced by the absence of Brucella seropositivity in goats (1/593 positive result) and dogs (0/315), which can be seen as potential spillover hosts. Therefore, the close proximity of brucellosis-infected wildlife is not a threat to domestic animals in this controlled setting with vaccination, fencing and movement control.

Successful Therapist-Parent Coaching: How In Vivo Feedback Relates to Parent Engagement in Parent-Child Interaction Therapy.

Although behavioral parent training is considered efficacious treatment for childhood conduct problems, not all families benefit equally from treatment. Some parents take longer to change their behaviors and others ultimately drop out. Understanding how therapist behaviors impact parental engagement is necessary to improve treatment utilization. This study investigated how different techniques of therapist in vivo feedback (i.e., coaching) influenced parent attrition and skill acquisition in parent-child interaction therapy (PCIT). Participants included 51 parent-child dyads who participated in PCIT. Children (age: M = 5.03, SD = 1.65) were predominately minorities (63% White Hispanic, 16% African American or Black). Eight families discontinued treatment prematurely. Therapist coaching techniques during the first session of treatment were coded using the Therapist-Parent Interaction Coding System, and parent behaviors were coded with the Dyadic Parent-Child Interaction Coding System, Third Edition. Parents who received more responsive coaching acquired child-centered parenting skills more quickly. Therapists used fewer responsive techniques and more drills with families who dropped out of treatment. A composite of therapist behaviors accurately predicted treatment completion for 86% of families. Although group membership was correctly classified for the treatment completers, only 1 dropout was accurately predicted. Findings suggest that therapist in vivo feedback techniques may impact parents' success in PCIT and that responsive coaching may be particularly relevant.

Neurophysiological signals of ignoring and attending are separable and related to performance during sustained intersensory attention.

The ability to attend to an input selectively while ignoring distracting sensations is thought to depend on the coordination of two processes: enhancement of target signals and attenuation of distractor signals. This implies that attending and ignoring may be dissociable neural processes and that they make separable contributions to behavioral outcomes of attention. In this study, we tested these hypotheses in the context of sustained attention by measuring neurophysiological responses to attended and ignored stimuli in a noncued, continuous, audiovisual selective attention task. We compared these against responses during a passive control to quantify effects of attending and ignoring separately. In both sensory modalities, responses to ignored stimuli were attenuated relative to a passive control, whereas responses to attended stimuli were enhanced. The scalp topographies and brain activations of these modulatory effects were consistent with the sensory regions that process each modality. They also included parietal and prefrontal activations that suggest these effects arise from interactions between top-down and sensory cortices. Most importantly, we found that both attending and ignoring processes contributed to task accuracy and that these effects were not correlated--suggesting unique neural trajectories. This conclusion was supported by the novel observation that attending and ignoring differed in timing and in active cortical regions. The data provide direct evidence for the separable contributions of attending and ignoring to behavioral outcomes of attention control during sustained intersensory attention.

Unravelling the maternal evolutionary history of the African leopard (Panthera pardus pardus).

The African leopard (Panthera pardus pardus) has lost a significant proportion of its historical range, notably in north-western Africa and South Africa. Recent studies have explored the genetic diversity and population structure of African leopards across the continent. A notable genetic observation is the presence of two divergent mitochondrial lineages, PAR-I and PAR-II. Both lineages appeared to be distributed widely, with PAR-II frequently found in southern Africa. Until now, no study has attempted to date the emergence of either lineage, assess haplotype distribution, or explore their evolutionary histories in any detail. To investigate these underappreciated questions, we compiled the largest and most geographically representative leopard data set of the mitochondrial NADH-5 gene to date. We combined samples (n = 33) collected in an altitudinal transect across the Mpumalanga province of South Africa, where two populations of leopard are known to be in genetic contact, with previously published sequences of African leopard (n = 211). We estimate that the maternal PAR-I and PAR-II lineages diverged approximately 0.7051 (0.4477-0.9632) million years ago (Ma). Through spatial and demographic analyses, we show that while PAR-I underwent a mid-Pleistocene population expansion resulting in several closely related haplotypes with little geographic structure across much of its range, PAR-II remained at constant size and may even have declined slightly in the last 0.1 Ma. The higher genetic drift experienced within PAR-II drove a greater degree of structure with little haplotype sharing and unique haplotypes in central Africa, the Cape, KwaZulu-Natal and the South African Highveld. The phylogeographic structure of PAR-II, with its increasing frequency southward and its exclusive occurrence in south-eastern South Africa, suggests that this lineage may have been isolated in South Africa during the mid-Pleistocene. This hypothesis is supported by historical changes in paleoclimate that promoted intense aridification around the Limpopo Basin between 1.0-0.6 Ma, potentially reducing gene flow and promoting genetic drift. Interestingly, we ascertained that the two nuclear DNA populations identified by a previous study as East and West Mpumalanga correspond to PAR-I and PAR-II, respectively, and that they have come into secondary contact in the Lowveld region of South Africa. Our results suggest a subdivision of African leopard mtDNA into two clades, with one occurring almost exclusively in South Africa, and we identify the potential environmental drivers of this observed structure. We caution that our results are based on a single mtDNA locus, but it nevertheless provides a hypothesis that can be further tested with a dense sample of nuclear DNA data, preferably whole genomes. If our interpretation holds true, it would provide the first genetic explanation for the smaller observed size of leopards at the southernmost end of their range in Africa.

Pupillary dilations in a Target/Distractor visual task paradigm and attention deficit hyperactivity disorder (ADHD).

ADHD is a neurocognitive disorder characterized by attention difficulties, hyperactivity, and impulsivity, often persisting into adulthood with substantial personal and societal consequences. Despite the importance of neurophysiological assessment and treatment monitoring tests, their availability outside of research settings remains limited. Cognitive neuroscience investigations have identified distinct components associated with ADHD, including deficits in sustained attention, inefficient enhancement of attended Targets, and altered suppression of ignored Distractors. In this study, we examined pupil activity in control and ADHD subjects during a sustained visual attention task specifically designed to evaluate the mechanisms underlying Target enhancement and Distractor suppression. Our findings revealed some distinguishing factors between the two groups which we discuss in light of their neurobiological implications.

A single-cell atlas of IL-23 inhibition in cutaneous psoriasis distinguishes clinical response.

Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was strongly attenuated. In contrast, poorly responsive patients were distinguished by persistent activation of IL-17-producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade-responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of >90% of IL-17-induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.

Dynamic activation of frontal, parietal, and sensory regions underlying anticipatory visual spatial attention.

Although it is well established that multiple frontal, parietal, and occipital regions in humans are involved in anticipatory deployment of visual spatial attention, less is known about the electrophysiological signals in each region across multiple subsecond periods of attentional deployment. We used MEG measures of cortical stimulus-locked, signal-averaged (event-related field) activity during a task in which a symbolic cue directed covert attention to the relevant location on each trial. Direction-specific attention effects occurred in different cortical regions for each of multiple time periods during the delay between the cue and imperative stimulus. A sequence of activation from V1/V2 to extrastriate, parietal, and frontal regions occurred within 110 ms after cue, possibly related to extraction of cue meaning. Direction-specific activations ∼300 ms after cue in frontal eye field (FEF), lateral intraparietal area (LIP), and cuneus support early covert targeting of the cued location. This was followed by coactivation of a frontal-parietal system [superior frontal gyrus (SFG), middle frontal gyrus (MFG), LIP, anterior intraparietal sulcus (IPSa)] that may coordinate the transition from targeting the cued location to sustained deployment of attention to both space and feature in the last period. The last period involved direction-specific activity in parietal regions and both dorsal and ventral sensory regions [LIP, IPSa, ventral IPS, lateral occipital region, and fusiform gyrus], which was accompanied by activation that was not direction specific in right hemisphere frontal regions (FEF, SFG, MFG). Behavioral performance corresponded with the magnitude of attention-related activity in different brain regions at each time period during deployment. The results add to the emerging electrophysiological characterization of different cortical networks that operate during anticipatory deployment of visual spatial attention.

Sarcopenia estimation using psoas major enhances P-POSSUM mortality prediction in older patients undergoing emergency laparotomy: cross-sectional study.

INTRODUCTION: Emergency laparotomy is a considerable component of a colorectal surgeon's workload and conveys substantial morbidity and mortality, particularly in older patients. Frailty is associated with poorer surgical outcomes. Frailty and sarcopenia assessment using Computed Tomography (CT) calculation of psoas major area predicts outcomes in elective and emergency surgery. Current risk predictors do not incorporate frailty metrics. We investigated whether sarcopenia measurement enhanced mortality prediction in over-65 s who underwent emergency laparotomy and emergency colorectal resection. METHODS: An analysis of data collected prospectively during the National Emergency Laparotomy Audit (NELA) was conducted. Psoas major (PM) cross-sectional area was measured at the L3 level and a ratio of PM to L3 vertebral body area (PML3) was calculated. Outcome measures included inpatient, 30-day and 90-day mortality. Statistical analysis was conducted using Mann-Whitney, Chi-squared and receiver operating characteristics (ROC). Logistic regression was conducted using P-POSSUM variables with and without the addition of PML3. RESULTS: Nine-hundred and forty-four over-65 s underwent emergency laparotomy from three United Kingdom hospitals were included. Median age was 76 years (IQR 70-82 years). Inpatient mortality was 21.9%, 30-day mortality was 16.3% and 90-day mortality was 20.7%. PML3 less than 0.39 for males and 0.31 for females indicated significantly worse outcomes (inpatient mortality 68% vs 5.6%, 30-day mortality 50.6% vs 4.0%,90-day mortality 64% vs 5.2%, p < 0.0001). PML3 was independently associated with mortality in multivariate analysis (p < 0.0001). Addition of PML3 to P-POSSUM variables improved area under the curve (AUC) on ROC analysis for inpatient mortality (P-POSSUM:0.78 vs P-POSSUM + PML3:0.917), 30-day mortality(P-POSSUM:0.802 vs P-POSSUM + PML3: 0.91) and 90-day mortality (P-POSSUM:0.79 vs P-POSSUM + PML3: 0.91). CONCLUSION: PML3 is an accurate predictor of mortality in over-65 s undergoing emergency laparotomy. Addition of PML3 to POSSUM appears to improve mortality risk prediction.

Open Retroperitoneal Repair for Complex Abdominal Aortic Aneurysms.

BACKGROUND: Open surgical repair (OSR) of complex abdominal aortic aneurysms (CAAAs) can be challenging. We frequently utilize the retroperitoneal (RP) approach for such cases. We audited our outcomes with the aim of establishing the utility and safety of this approach. METHODS: Retrospective analysis was performed of all patients undergoing OSR of an unruptured CAAA via a RP approach in our center over a 7-year period. Data on repairs via a transperitoneal (TP) approach were collected to provide context. Demographic, operative, radiological, and biochemical data were collected. The primary outcome measure was 30-day/inpatient mortality. Secondary outcomes included the need for reoperation, incidence of postoperative chest infection, acute kidney injury (AKI) and length of stay (LOS). All patients received aortic clamping above at least one main renal artery. RESULTS: One hundred and three patients underwent OSR of an unruptured CAAA; 55 via a RP approach, 48 TP. The RP group demonstrated a more advanced pattern of disease with a larger median maximum diameter (65 vs. 61 mm, p= 0.013) and a more proximal extent. Consequently, the rate of supravisceral clamping was higher in RP repair (66 vs. 15%, p < 0.001). Despite this there were no differences in the observed early mortality (9.1 vs. 10%, NS); incidence of reoperation (10.9 vs. 12.5%, NS), chest infection (32.7 vs. 25%, NS), and AKI (52.7 vs. 45.8%, NS); or median LOS (10 vs. 12 days, NS) following RP and TP repair. CONCLUSION: OSR of CAAAs carries significant 30-day mortality. In patients unsuitable for fenestrated endovascular aortic repair or those desiring a durable long-term solution, OSR can be performed through the RP or TP approach. This study has demonstrated that in our unit RP repair facilitates treatment of more advanced AAA utilizing complex proximal clamp zones with similar perioperative morbidity and mortality compared with TP cases utilizing more distal clamping.

Adolescent smokers show decreased brain responses to pleasurable food images compared with nonsmokers.

INTRODUCTION: Nicotine acts on the mesocorticolimbic circuits of the brain leading to the release of dopamine. Repeated elevations of dopamine in the brain may cause smokers to become less sensitive to "natural reinforcers." To test the theory that adolescents with low nicotine exposure may already have decreased activation when exposed to a natural reinforcer, we looked at the effect of visual cues representing "pleasurable" food on light adolescent smokers compared with nonsmokers. METHODS: Twelve adolescent light smokers (aged 13-17 years, smoked 1-5 cigarettes/day) and 12 nonsmokers (aged 13-17 years, never smoked a cigarette) from the San Francisco Bay Area underwent functional magnetic resonance imaging scanning. During scanning, they viewed blocks of photographic images representing pleasurable foods (sweet, high fat, and salty foods) and control cues. RESULTS: Smokers reported smoking a mean of 3.6 cigarettes/day. There was no difference in body mass index between groups (24.1 vs. 24.0, respectively, p = .99). Food images elicited greater activations in nonsmokers in multiple areas including the insula (T = 4.38, p < .001), inferior frontal region (T = 5.12, p < .001), and rolandic operculum (T = 6.18, p < .001). There were no regions where smokers demonstrated greater blood oxygenation level-dependent activations compared with nonsmokers when viewing food versus neutral images. CONCLUSIONS: The finding of decreased activation to pleasurable food among adolescent light smokers supports the theory that these adolescents are displaying decreased sensitivity to at least one natural reinforcer. This also supports the theory that nicotine may affect the brain early in the trajectory of smoking, thus underscoring the need for early intervention among adolescent smokers.

Brucellosis in wildlife in Africa: a systematic review and meta-analysis.

This study aimed to consolidate current knowledge of wildlife brucellosis in Africa and to analyse available predictors of infection. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Information on species, test used, test results, area, rainfall, livestock and wildlife contact and year of study were extracted. This systematic review revealed 42 prevalence studies, nine disease control articles and six articles on epidemiology. Brucella abortus, Brucella melitensis, Brucella inopinata and Brucella suis were reported in wildlife. The prevalence studies revealed serological evidence of brucellosis in buffalo, antelope (positive in 14/28 species), carnivores (4/12) and other species (7/20) over the last five decades. Buffalo populations were more likely to be infected and had a higher seroprevalence than other species; the pooled seroprevalence was 13.7% (95% CI 10.3-17.3%) in buffalo, 7.1% (95% CI 1.1-15.5%) in carnivores and 2.1% (95% CI 0.1-4.9%) in antelope. Wildlife in high rainfall areas (≥ 800 mm) were more likely to be infected, and infected populations showed higher seroprevalence in high rainfall areas and in studies published after 2000. Domestic animal contact was associated with increased seroprevalence in antelope and carnivore species, but not in buffalo, supporting the hypothesis that buffalo may be a reservoir species.

Pre-operative psoas major measurement compared to P-POSSUM as a prognostic indicator in over-80s undergoing emergency laparotomy.

INTRODUCTION: Emergency laparotomy in patients over the age of 80 is associated with high morbidity and mortality. Accurate risk prediction in this patient population is desirable. Sarcopenia has been shown to be associated with outcome in multiple clinical settings and the psoas major muscle as measured on computed tomography (CT) imaging has been demonstrated as a marker of sarcopenia. We aim to assess the use of psoas major measurement on pre-operative CT as a prognostic indicator in over-80s undergoing emergency laparotomy and compare this measurement to P-POSSUM. METHODS: A retrospective interrogation of the prospectively collected National Emergency Laparotomy Database including all over-80s undergoing emergency laparotomy between January 2014 and September 2016 was conducted. Demographic, operative data and P-POSSUM data were collected and analysed. Computed tomography (CT) images were accessed and analysed, and cross-sectional areas of psoas major and the corresponding lumbar vertebral body at the level of the L3 inferior end plate were calculated. The ratio of psoas major-to-L3 cross-sectional area (PM:L3) was calculated for each patient. Mann-Whitney U test and receiver-operating characteristics (ROC) curves were used for statistical analysis. RESULTS: One hundred and three over-80s underwent emergency laparotomy. Male:female ratio was 60:43. Median age was 84 years (range 80-98 years). 30-day mortality was 19.4%.90-day mortality was 25.2%. Median PM:L3 ratio in patients who died as an inpatient was 0.3 and PM:L3 ratio in patients who survived to discharge was 0.52 (p < 0.0001). Median PM:L3 ratio in patient who died within 30 days post-op was 0.28 and 0.48 in those patients who survived to 30 days (p < 0.0001). Median PM:L3 ratio in patient who died within 90 days post-op was 0.28 and 0.51 in those patients who survived to 90 days (p < 0.0001). ROC analysis gave an area under the curve (AUC) of 0.85 for in-patient mortality, 0.86 for 30-day mortality, and 0.88 for 90-day mortality. ROC analysis for P-POSSUM in this data set demonstrated an AUC of 0.51 for in-patient mortality and 0.75 for 30- and 90-day mortality. CONCLUSION: CT imaging of the abdomen and pelvis is routinely used in over-80s prior to emergency laparotomy making PM:L3 calculation feasible for the majority of patients in this group. PM:L3 ratio is a useful prognostic indicator for prediction of mortality in patients over the age of 80. PM:L3 is superior to the P-POSSUM score in this series.

Sero-Epidemiological Study of Selected Zoonotic and Abortifacient Pathogens in Cattle at a Wildlife-Livestock Interface in South Africa.

A cross sectional sero-epidemiological study was conducted on cattle in a communal farming area adjacent to Kruger National Park at a wildlife-livestock interface in South Africa. A total of 184 cattle were screened for exposure to 5 abortifacient or zoonotic pathogens, namely Coxiella burnetii, Toxoplasma gondii, Chlamydophila abortus, Neospora caninum, and Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assays. In addition, the virus neutralization test was used to confirm the presence of antibodies to RVFV. The seroprevalence of C. burnetii, T. gondii, C. abortus, N. caninum, and RVFV antibodies was 38.0%, 32.6%, 20.7%, 1.6%, and 0.5%, respectively, and varied between locations (p < 0.001). Seroprevalence of C. burnetii and T. gondii was highly clustered by location (intraclass correlation coefficient [ICC] = 0.57), and that of C. abortus moderately so (ICC = 0.11). Seroprevalence was not associated with sex or age for any pathogen, except for C. abortus, for which seroprevalence was positively associated with age (p = 0.01). The predominant mixed infections were C. burnetii and T. gondii (15.2%) and C. burnetii, T. gondii, and C. abortus (13.0%). The serological detection of the five abortifacient pathogens in cattle indicates the potential for economic losses to livestock farmers, health impacts to domestic animals, transmission across the livestock-wildlife interface, and the risk of zoonotic transmission. This is the first documentation of T. gondii infection in cattle in South Africa, while exposure to C. burnetii, C. abortus, and N. caninum infections is being reported for the first time in cattle in a wildlife-livestock interface in the country.

Treatment of anxiety in older adolescents and young adults with autism spectrum disorders: A pilot study.

Anxiety disorders are commonly comorbid in adolescents and young adults with high-functioning autism. Cognitive-behavioral treatments (CBT) for anxiety, when adapted and expanded to target autism spectrum disorder (ASD) characteristics, may be beneficial, but there is minimal evidence to guide clinicians in their application. This multiple-baseline design study evaluated the initial efficacy of a CBT protocol adapted to address anxiety symptoms and adaptive functioning in this population. Anxiety and ASD symptoms were assessed for six participants at intake, after baseline, posttreatment, and at 1-month follow-up. Parent- and child-reported anxiety was also assessed during baseline and treatment. Visual inspection and reliable change index scores were used to evaluate change. All participants improved on clinician-rated measures of disorder severity, and gains were maintained at follow-up. Results were more equivocal for parent- and self-rated anxiety and parent-rated ASD, partly because of spontaneous changes during baseline.

Phase locking of single neuron activity to theta oscillations during working memory in monkey extrastriate visual cortex.

Working memory has been linked to elevated single neuron discharge in monkeys and to oscillatory changes in the human EEG, but the relation between these effects has remained largely unexplored. We addressed this question by measuring local field potentials and single unit activity simultaneously from multiple electrodes placed in extrastriate visual cortex while monkeys were performing a working memory task. We describe a significant enhancement in theta band energy during the delay period. Theta oscillations had a systematic effect on single neuron activity, with neurons emitting more action potentials near their preferred angle of each theta cycle. Sample-selective delay activity was enhanced if only action potentials emitted near the preferred theta angle were considered. Our results suggest that extrastriate visual cortex is involved in short-term maintenance of information and that theta oscillations provide a mechanism for structuring the recurrent interaction between neurons in different brain regions that underlie working memory.

A novel ANCOVA design for analysis of MEG data with application to a visual attention study.

Statistical inference from MEG-based distributed activation maps is well suited to the general linear modeling framework, a standard approach to the analysis of fMRI and PET neuroimaging studies. However, there are important differences from the other neuroimaging modalities related to how observations are created and fitted in GLM models, as well as how subsequent statistical inference is performed. In this paper, we demonstrate how MEG oscillatory components can be analyzed in this framework based on a custom ANCOVA model that takes into account baseline and inter-hemispheric effects, rather than a simpler ANOVA design. We present the methodology using as an example an MEG study of visual spatial attention, since the model design depends on the specific experiment and neuroscience hypotheses being tested. However, the techniques presented here can be readily adapted to accommodate other experimental paradigms. We create statistics that estimate the temporal evolution of attention effects on alpha power in several cortical regions. We present evidence for direction-specific attention effects on alpha activity in occipital and parietal regions and demonstrate the sub-second timing of these effects in each region. The results support a mechanism for anticipatory attentional deployment that dynamically modulates the local alpha synchrony in a network of parietal control and occipital sensory regions.

Deficit in a neural correlate of reality monitoring in schizophrenia patients.

Patients who suffer from the devastating psychiatric illness schizophrenia are plagued by hallucinations, bizarre behavior, and delusional ideas, such as believing that they are controlled by malevolent outside forces. A fundamental human cognitive operation that may contribute to these hallmark symptoms is the ability to maintain accurate and coherent self-referential processing over time, such as occurs during reality monitoring (distinguishing self-generated from externally perceived information). However, the neural bases for a disturbance in this operation in schizophrenia have not been fully explored. Using functional magnetic resonance imaging, we asked clinically stable schizophrenia patients to remember whether or not they had generated a target word during an earlier sentence completion task. We found that, during accurate performance of this self-referential source memory task, the schizophrenia subjects manifest a deficit in rostral medial prefrontal cortex (mPFC) activity--a brain region critically implicated in both the instantiation and the retrieval of self-referential information in healthy subjects. Impairment in rostral mPFC function likely plays a key role in the profound subjective disturbances that characterize schizophrenia and that are the aspect of the disorder most troubling to patients and to society at large.

Giant verrucous nodules in a patient with tuberculosis.

Sarcoidosis is a systemic inflammatory disorder characterized histologically by noncaseating granulomas in affected organs. Cutaneous manifestations of the disease such as papules, nodules, plaques, and ulcerations occur in approximately 25% of the patients. Sarcoidosis can present with multiple different morphologies including annular, psoriasiform, ichthyosiform, morpheaform, and verrucous. In this study, we report a 30-year-old African American man with a history of spinal tuberculosis as a child and slowly enlarging verrucous nodules that appeared at the age of 5 years. After an extensive infectious disease evaluation, the diagnosis of verrucous sarcoidosis was established with the presence of noncaseating granulomas and a completely negative workup for infectious etiologies.

Paradoxical effects of cost reduction measures in managed care systems for treatment of severe psoriasis.

BACKGROUND: Insurance companies vary widely in their coverage policies for severe psoriasis therapies. Unfortunately, coverage policies for psoriasis therapies do not necessarily follow current treatment paradigms, such that more expensive second or third line treatments may be more easily obtained than first line treatments. METHODS: We reviewed insurance policy bulletins, statements of coverage/medical necessity, and prior authorization forms for three large insurance carriers regarding psoriasis treatment with biologic agents and phototherapy. A cost comparison was performed to estimate total costs to patients and insurer under the current system as well as a hypothetical system in which co-pays and deductibles are eliminated. Additionally, we reviewed the total cost to an insurer for placing a patient on a trial of home phototherapy before approving use of expensive biologics. RESULTS: Requirements for coverage for phototherapy treatments are often the same, if not more stringent, than those for biologics. On an annual per patient basis, insurance companies pay an estimated $5, $76, and $23,408 for home phototherapy, office phototherapy, and biologics, respectively. The first year cost to patients, however, is estimated to be $2,590, $3,040, and $920 for home phototherapy, office phototherapy, and biologics, respectively. An initial 3-month trial of home phototherapy yields a graded annual cost savings to insurers of $21,610 to $2,110 per patient. DISCUSSION: The evolution of psoriasis treatment has resulted in a paradoxical situation in which the use of lower-cost psoriasis treatments, with longer safety track records, is discouraged relative to newer options. If co-pays, deductibles, and prior authorization requirements that discourage phototherapy were reduced or eliminated, more patients and physicians would likely choose phototherapy over biologics. This has the potential to reduce overall healthcare costs for psoriasis management.