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Science fiction criticism has long attended the relationship between form and utopian thought. However, increased study of Latin American narratives has allowed for a return to foundational science fiction theories with renewed perspective. While critics have recognized the tendency of Latin American science fiction to slip between genres, a trend termed the “slipstream phenomenon,” there has been little analysis of its impact on utopian imagination. As a result, we miss one of the region's most unique contributions to broader science fiction traditions. In response, this article locates Samanta Schweblin's Kentukis (2018) within the legacies of cyberpunk and argues that the novel uses slipstream to establish and dismantle a series of classic utopian horizons by shifting its genre identity. In doing so, this work identifies a turn in recent Latin American science fiction that metacritically questions the ability of science fiction form itself to imagine a utopian horizon beyond global capitalism.

Peripheral neuropathies commonly affect quality of life of patients due to pain, sleep disturbances, and fatigue, although trials have not adequately explored these domains of care. The aim of this study was to assess the impact of nortriptyline, duloxetine, pregabalin, and mexiletine on pain, sleep, and fatigue in patients diagnosed with cryptogenic sensory polyneuropathy (CSPN).We implemented a Bayesian adaptive design to perform a 12-wk multisite, randomized, prospective, open-label comparative effectiveness study in 402 CSPN patients. Participants received either nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69). At prespecified analysis timepoints, secondary outcomes, Patient Reported Outcomes Measurement Information System (PROMIS) surveys including Short Form (SF)-12, pain interference, fatigue, and sleep disturbance, were collected.Mexiletine had the highest quit rate (58%) due to gastrointestinal side effects, while nortriptyline (38%) and duloxetine (38%) had the lowest quit rates. If tolerated for the full 12 wk of the study, mexiletine had the highest probability (90%) of positive outcomes for improvements in pain interference and fatigue. There was no significant difference among the medications for sleep disturbance or SF-12 scores. Adverse events and lack of efficacy were the two most common reasons for cessation of therapy.Physicians caring for patients with CSPN should consider mexiletine to address pain and fatigue, although nortriptyline and duloxetine are better medications to trial first since they are better tolerated. Future research should compare other commonly used medications for CSPN to determine evidence-based treatment strategies.

Muscular dystrophies are inherited disorders that are characterized by progressive muscle degeneration. These disorders are caused by mutation in the genes encoding structural elements within the muscle, which leads to increased vulnerability to mechanical stress and sarcolemma damage. Although myofibers have the capacity to regenerate, the newly formed myofibers still harbor the genetic mutation, which induces continuous cycles of muscle fiber death and regeneration. This repeated cycling is accompanied by an inflammatory response which eventually provokes excessive fibrotic deposition. The histopathological changes in skeletal muscle tissue are central to the disease pathogenesis. Analysis of muscle histopathology is the gold standard for monitoring muscle health and disease progression. However, manual, or semi-manual quantification methods are not only immensely tedious but can be subjective. Here, we present four image analysis pipelines built in CellProfiler which enable users without a background in computer vision or programming to quantitatively analyze biological images. These image analysis pipelines are designed to quantify skeletal muscle histopathological staining for membrane damage, the abundance and size distribution of regenerating muscle fibers, inflammation via quantification of CD68 + M1 macrophages, and collagen deposition. Additionally, we discuss methods to address common errors associated with the quantification of microscopy images. These automated tools can not only improve workflow efficiency but can provide a better understanding of the histopathological progression of muscular dystrophy.

Computational modeling can provide a mechanistic and quantitative framework for describing intracellular spatial heterogeneity of solutes such as oxygen partial pressure (pO2). This study develops and evaluates a finite-element model of oxygen-consuming mitochondrial bioenergetics using the COMSOL Multiphysics program. The model derives steady-state oxygen (O2) distributions from Fickian diffusion and Michaelis–Menten consumption kinetics in the mitochondria and cytoplasm. Intrinsic model parameters such as diffusivity and maximum consumption rate were estimated from previously published values for isolated and intact mitochondria. The model was compared with experimental data collected for the intracellular and mitochondrial pO2 levels in human cervical cancer cells (HeLa) in different respiratory states and under different levels of imposed pO2. Experimental pO2 gradients were measured using lifetime imaging of a Förster resonance energy transfer (FRET)-based O2 sensor, Myoglobin-mCherry, which offers in situ real-time and noninvasive measurements of subcellular pO2 in living cells. On the basis of these results, the model qualitatively predicted (1) the integrated experimental data from mitochondria under diverse experimental conditions, and (2) the impact of changes in one or more mitochondrial processes on overall bioenergetics.

Nucleophosmin 1 (NPM1) mutation is the primary genetic lesion in adult acute myeloid leukemia (AML). Typically, a nucleolar protein, NPM1 mutations cause cytoplasmic delocalization of NPM1(NPM1c+), triggering leukemogenesis. Interestingly, NPM1c+ mutation confers enhanced chemosensitivity. However, the mechanism underlying NPM1c+ mutation-induced oncogenesis or chemosensitivity remains unclear. We previously reported that, in response to genotoxic stimuli, NPM1 forms a platform for caspase-2 activation in the nucleolus. Caspase-2 is a pro-apoptotic protein and a known tumor suppressor. Our results indicate that nucleolar caspase-2 activation is specific to NPM1wt cells. In the NPM1c+ cells, caspase-2 activation is exclusively cytosolic, suggesting that caspase-2 is activated in the same sub-cellular compartment as NPM1 localization. Loss of caspase-2 rescued the increased sensitivity of NPM1c+ cells to apoptotic cell death. This is accompanied by reduced cleavage of the apoptotic substrate, caspase-3. Notably, caspase-2 deficient NPM1wt cells showed no significant difference in the percentage of apoptotic cell death or endogenous substrate cleavage compared to its caspase-2 wild-type counterpart. This suggests that caspase-2 may contribute to the chemosensitivity of NPM1c+ cells. Strikingly, in unstimulated cells, loss of caspase-2 leads to prolonged G1 arrest and progressive loss of cell viability. Immunophenotyping of NPM1c+ cells revealed a remarkable increase in the CD14+population representing monocyte/macrophage-like features, suggesting that loss of caspase-2 results in terminal differentiation. Exogenous expression of NPM1c+ in caspase-2 deficient NPM1wt cells impaired viability, confirming that NPM1c+ cells require caspase-2 for its growth and proliferation. Transcriptomic analysis revealed that loss of caspase-2 significantly downregulates pathways involved in stem cell pluripotency. In particular, FGF2, IGFR, WNT, LIF, and one of the core members of the self-renewal transcription factor, OCT 4, were downregulated in the absence of caspase-2 in NPM1c+ cells. This reveals a novel role for caspase-2 in maintaining NPM1c+ AML stemness. Taken together, our study shows that NPM1c+ mediated caspase-2 activation regulates AML cell death and survival cascades, a key determinant of chemosensitivity and leukemogenesis. Citation Format: Dharaniya Sakthivel, Alexandra Brown-Suedel, Francesca Keane, F. Kenneth McSherry, Chloe I. Charendoff, Kevin Dunne, Dexter Robichaux, Jonathan M. Flanagan, Lisa Bouchier-Hayes. The role of nucleophosmin1 mediated caspase2 activation in acute myeloid leukemia cell death and cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB035.

Curated by architect and industrial designer Emilio Ambasz, The Museum of Modern Art’s 1976 exhibition ‘The Taxi Project: Realistic Solutions for Today’ involved the development and display of five...

Background: oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. Methods: all available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki67 2wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. Findings: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki67 2wk (p2wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. Interpretation: our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. Funding: Cancer Research UK (CRUK/07/015).

Although biological iron-sulfur (Fe–S) clusters perform some of the most difficult redox reactions in Nature, they are thought to be composed exclusively of Fe2+ and Fe3+ ions, as well as mixed-valent pairs with average oxidation states of Fe2.5+. We herein show that Fe–S clusters formally composed of these valences can access a wider range of electronic configurations—in particular, those featuring low-valent Fe1+ centers. We demonstrate that CO binding to a synthetic [Fe4S4]0 cluster supported by N-heterocyclic carbene ligands induces generation of Fe1+ centers via intracluster electron transfer, wherein a neighboring pair of Fe2+ sites reduces the CO-bound site to a low-valent Fe1+ state. Similarly, CO binding to an [Fe4S4]+ cluster induces electron delocalization with a neighboring Fe site to form a mixed-valent Fe1.5+Fe2.5+ pair in which the CO-bound site adopts partial low-valent character. These low-valent configurations engender remarkable C–O bond activation without having to traverse highly negative and physiologically inaccessible Fe2+/Fe1+ redox couples.

In this secondary analysis of the Rural Engagement in Primary Care for Optimizing Weight Reduction (RE-POWER) randomized trial, the authors determined the effectiveness of weight-loss interventions in people with diabetes compared with those without diabetes living in rural areas.The RE-POWER study was a randomized trial designed to determine the effectiveness of nonpharmacological behavioral weight-loss interventions in rural participants with obesity, comparing the individual in-clinic visit model to in-person group sessions and phone group sessions over 24 months. In this secondary analysis, weight loss was compared in participants with and without diabetes. The effects of factors such as medications, insulin, and behavioral factors were compared.Participants with diabetes were less likely to lose weight during the study compared with those without diabetes up to 18 months (4.12% vs. 5.31%; net difference = 1.46%; 95% CI: 0.63%-2.28%). Participants with diabetes on insulin lost less weight than patients with diabetes not on insulin at 6 months (4.52% vs. 6.88%; net difference = 2.35%; 95% CI: 0.55%-4.16%). The group with diabetes had significantly lower changes in blood pressure and lipid parameters versus the group without diabetes.Patients with diabetes in rural areas were less likely to lose weight, and metabolic parameters were less responsive to weight loss, compared with patients without diabetes.

© 2021 Elsevier Ltd. All rights reserved., Children and young people have been deeply affected by the COVID-19 pandemic. Lockdowns and new ways of living have necessitated massive adjustments. Despite heroic efforts from teachers, there has been a huge impact on education, and children lost the psychosocial benefits of being in school. News coverage is incessant, and polarised narratives and opinions are amplified in social media echo-chambers. In this report, co-authored with an adolescent from our clinic, we discuss the psychological impact of the COVID-19 pandemic on children and young people with respiratory problems.

The following paper takes as its starting point a posed photograph of the members’ room space within the Architectural Association’s AA125 exhibition. The image is one of the only published traces ...

At the buried Atlantida deposit (Cu–Au–(Mo)) in the Atacama Desert of Chile, highly saline pockets of fine-grained material 10 cm–3 m in diameter were identified on the alluvial surface using remote sensing and detailed regolith mapping. The median salinity (NaCl dominant) of the saline pockets is 2.2% compared to background alluvial material with a median salinity of 0.01%. Their distribution along mapped fault structures and the highly saline nature of the material suggest they form as an expression of groundwater forced through fractures to the surface during seismic activity. A targeted geochemical survey, oriented parallel to the orientation of the structures (sample spacing 250 m along structural trend) specifically sampling saline pockets on relatively old surfaces, was performed over the deposit. Deionized water extraction of soluble salts and analysis by inductively coupled plasma mass spectrometry revealed strong correlations of increasing salinity and increasing concentrations of porphyry copper pathfinder elements. Elevated responses of Se, Mo, Re and Te normalized to a groundwater volume proxy are present directly over the Atlantida deposit. This suggests the rate of erosion and sedimentation is slow enough in the Atacama Desert to preserve surficial anomalies as saline pockets, formed by periodic seismically induced surface flooding of groundwater along faults extending to surface. Targeted sampling of saline pockets along structural trends using weak leach geochemistry in terrains dominated by transported cover can serve as a routine exploration method for the potential discovery of buried copper porphyries and other styles of mineralization in the Atacama Desert of Chile.

Domestic violence (DV) impacts women’s mental health. DV survivors need access to services that can effectively assure safety and healing. DV service providers are positioned to provide accommodations for survivors who are experiencing mental health disability in order for survivors to fully engage with and benefit from DV-related services. Using qualitative methods, 11 focus groups were conducted with staff (n = 45) and administrators (n = 17) from five DV advocacy agencies and shelters in a Midwest state of the US to assess service providers’ needs related to working with survivors with mental health disability. Participants shared their personal experiences and challenges of working with survivors who have mental health disability. Findings point to the need to further build capacity within agencies to respond to the complex mental health needs of survivors. These findings also indicate the need for DV agencies to effectively implement integrated trauma informed care models that promote healing when working with DV survivors who have mental health disability.

Domestic violence (DV) survivors are susceptible to traumatic and anoxic-hypoxic brain injury, collectively referred to as brain injury (BI). This study characterized: 1) provider perception of the...

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant’s DHA status at delivery is known as maternal–newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants (n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study.

BACKGROUND As the cost of clinical trials continues to rise, novel approaches are required to ensure ethical allocation of resources. Multisite trials have been increasingly utilized in phase 1 trials for rare diseases and in phase 2 and 3 trials to meet accrual needs. The benefits of multisite trials include easier patient recruitment, expanded generalizability, and more robust statistical analyses. However, there are several problems more likely to arise in multisite trials, including accrual inequality, protocol nonadherence, data entry mistakes, and data integration difficulties. OBJECTIVE The Biostatistics & Data Science department at the University of Kansas Medical Center developed a clinical trial management system (comprehensive research information system [CRIS]) specifically designed to streamline multisite clinical trial management. METHODS A National Institute of Child Health and Human Development–funded phase 3 trial, the ADORE (assessment of docosahexaenoic acid [DHA] on reducing early preterm birth) trial fully utilized CRIS to provide automated accrual reports, centralize data capture, automate trial completion reports, and streamline data harmonization. RESULTS Using the ADORE trial as an example, we describe the utility of CRIS in database design, regulatory compliance, training standardization, study management, and automated reporting. Our goal is to continue to build a CRIS through use in subsequent multisite trials. Reports generated to suit the needs of future studies will be available as templates. CONCLUSIONS The implementation of similar tools and systems could provide significant cost-saving and operational benefit to multisite trials. CLINICALTRIAL ClinicalTrials.gov NCT02626299; https://tinyurl.com/j6erphcj

BACKGROUND: The rate of AD for African Americans (AAs) is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress, and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs.OBJECTIVE: Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race.METHODS: We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound, and cognitive testing.RESULTS: While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less cerebrospinal fluid tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, race significantly modified the relationship between total tau, phospho-tau, and Trails B, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs.CONCLUSION: In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.

Founded in 2010 by Sydney-based artist and academic Sarah Breen Lovett, Expanded Architecture is a multidisciplinary curatorial project that has, across a number of iterations, incorporated film, p...

Post-operative atrial fibrillation (POAF) is a common, self-limiting complication following non-cardiac surgery. It is associated with other complications such as pneumonia and sepsis, increased hospital stay and in-hospital mortality. The aim of the study is to identify risk factors, morbidity and mortality associated with POAF. METHODS Retrospective cohort study of 571 consecutive patients who presented for colorectal surgery at The Canberra Hospital. Seventy-four patients were excluded due to history of atrial fibrillation and a further 124 patients were lost to follow-up at 1 year. Patient characteristics, intraoperative factors and post-operative outcomes were retrospectively collected. One-year mortality data were collected for 373 patients in the cohort. RESULTS A total of 497 patients were included, 33 (6.6%) developed POAF within 30 days of surgery. POAF is associated with ischaemic heart disease (24.2 versus 11.6%, P = 0.035), emergency (66.7 versus 34.1%, P = 0.0001) and open procedures (87.9 versus 70.9%, P = 0.036). There is a higher incidence of post-operative complications including pneumonia (24.2 versus 9.1%, P = 0.006), abdominal collection (21.2 versus 9.7%, P = 0.049) and sepsis (21.2 versus 7.5%, P

Exploring the interactions between liquid surfaces and their relationship to the figure of the fille fatale in dark genres of film and television, this paper suggests that the liquid surface not only disrupts our understanding of architecture as a static structural envelope, but also acts to destabilise the image of the innocent girl in science fiction and horror films and television. The discussion focuses on three relatively recent depictions of young girls who confront (or are forced to confront) the liquid surface: Mitsuko’s submersion in the water vessels of an apartment building in Dark Water (2002), Ofelia and the muddy interior of the tree in Pan’s Labyrinth (2006), and the watery floor of Eleven’s psychic state in Stranger Things (2016). Working with Jill Stoner’s understanding of minor architectures and their ability to deterritorialise both physical structures and structures of power, the paper asks to what extent the liquid surface encounters of Ofelia, Mitsuko and Eleven exist as reflections of each character’s experiences, or as currents of agency through which the fille fatale reshapes her world. In doing so the research considers the ways in which fictional liquid surfaces operate as a visual minor architecture that elicits a questioning of social and physical norms.

Chiral ionic liquids show promising applications in various different fields. A series of pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was prepared in good yields using an efficient, economic and simple pathway. The chirality was introduced using ( l )-lactate and ( l )-menthol derivatives. The resultant chiral compounds were characterized by both spectroscopy and polarimetry. We envision that these new chiral compounds can serve as effective reaction media and chiral catalysts for asymmetric reactions, which are presently being investigated in our lab.

The aim of this paper is to explore the impact of monetary policy decisions by the Reserve Bank of Australia on the Australian stock market. We find some evidence that equity prices are negatively impacted by unexpected changes in the target cash rate. The result is generally consistent with existing studies that use US data in the analysis. We show that the stock market does not react to raw changes in the target cash rate, the expected component of raw cash rate changes, and the release of the explanatory meeting minutes. [ABSTRACT FROM AUTHOR]

High schools in the United States are increasingly requiring their students to complete financial education prior to graduation. This study estimates the effects of these requirements on the credit report outcomes of 18- through 21-year-olds—young people just establishing their financial independence. We find that financial education requirements are associated with fewer defaults and higher credit scores among young adults, but this general finding masks important heterogeneity at the state level. We conclude that well-funded teacher preparation may be key to successfully implementing financial education programs.

RATIONALE Cigarette smoke (CS) is the major risk factor in development of chronic obstructive pulmonary disease (COPD). Interventions that can prevent and/or reverse disease are urgently needed. Hydrogen sulfide (H2S) is generated in mitochondria (mt) and crucial in maintaining mt respiration, suppressing oxidative stress/inflammation. Lung H2S levels are reduced after CS exposure. Lung inflammation, mitochondrial damage and oxidative injury are exacerbated as a result of inhibition/silencing of H2S enzymes, suggesting impairment of H2S synthesis/loss of bioavailability is detrimental in COPD and negatively impacts mitochondrial health. METHODS We have produced novel mt-targeted H2S donors (mtH2SD) AP39 and RT01 to investigate whether these molecules could suppress and/or reverse CS-induced inflammation and lung injury. To investigate suppression, mice were exposed to CS (or air) for 8 wks (with 1.0 mg/kg). To investigate reversal, mice were exposed to CS for 8 wks followed by either 4 wks rest or continued CS exposure, each with mtH2SD (1.0 mg/kg). Airway inflammation (BALF differential cell counts, IL-1β by ELISA) and lung function were assessed. RESULTS Lung H2S levels were reduced and inflammasome activity increased in response to CS exposure. mtH2SD significantly suppressed CS-induced alveolar destruction, fibrosis and improved lung function. mtH2SD treatment reversed CS-induced lung neutrophil, eosinophil and macrophage infiltration, loss of lung function, and partially reversed airway resistance in both models. CONCLUSIONS Targeting H2S to mitochondria may be a novel therapeutic approach to prevent and/or reverse mitochondria-driven inflammation and lung injury in COPD and related diseases.

To switch patients with ulcerative colitis (UC) from costlier 5-aminosalicylic acid compounds to sulfasalazine and assess (1) the cost savings, (2) the barriers to switching, and (3) adverse events (AEs) and adherence at 3 months after the drug switch.An open-label, pharmacist-administered drug switch program coordinated at an academic inflammatory bowel disease center.A clinical pharmacist contacted patients with UC who were prescreened by physicians and covered by specific insurers to enroll them in the drug switch program. Enrolled patients were followed for 3 months to assess AEs and medication adherence. Reasons for declining to participate were recorded.A total of 205 eligible patients were identified; only 14 enrolled, and 10 remained on sulfasalazine for the entire 3-month follow-up period. The enrollment rate was only 4.9%, yet a net cost savings of $22,828/3-month to the insurer was achieved (including program administration costs but excluding AE costs), with co-pays reduced by approximately $25 per month per patient. The rate of AEs on sulfasalazine (28.6%) was similar to that found in previous reports. Significant unanticipated barriers to switching were encountered, namely patient desire to not alter an existing effective drug regimen.A pharmacist-administered drug switch program in patients with UC was significantly more difficult than anticipated, with questionable achievement of cost savings. This experience suggests that future drug switches and studies should focus on patient preferences for drug switching, as this may have implications for switching from brand name to biosimilar drugs.

Research indicates that certain antihypertensive medications alter Alzheimer's disease (AD) biomarkers in Caucasians. The renin angiotensin system (RAS) regulates blood pressure (BP) in the body and the brain and may directly influence AD biomarkers, including amyloid-β (Aβ) neuropathology, cerebral blood flow (CBF), and inflammatory markers. This hypothesis is supported by studies, including ours, showing that antihypertensives targeting the RAS reduce the risk and slow the progression of AD in Caucasians. While mounting evidence supports a protective role of RAS medications in Caucasians, this mechanism has not been explored in African Americans. To assess the mechanism by which RAS medications modify the brain RAS, cerebrospinal fluid (CSF) Aβ, CBF, and inflammatory markers in African Americans, we are conducting an eight month, Phase Ib randomized, placebo controlled trial, enrolling 60 middle-aged (45-70 years), non-demented individuals, at risk for AD by virtue of a parental history. Participants include normotensive and treated hypertensives that have never been exposed to a RAS medication. Participants are randomized (1 : 1:1) by gender and BP medication use (yes/no) to one of three groups: placebo, or 20 mg, or 40 mg telmisartan (Micardis), to determine the dose required to penetrate the CNS. Our overarching hypothesis is that, compared to placebo, both doses of telmisartan will penetrate the CNS and produce salutary, dose dependent effects on the brain RAS as well as CSF Aβ, CBF, and CSF inflammatory markers in African Americans, over eight months. This manuscript describes the trial rationale and design.

Post-operative atrial fibrillation (POAF) is a common, self-limiting complication following non-cardiac surgery. It is associated with other complications such as pneumonia and sepsis, increased hospital stay and in-hospital mortality. The aim of the study is to identify risk factors, morbidity and mortality associated with POAF.Retrospective cohort study of 571 consecutive patients who presented for colorectal surgery at The Canberra Hospital. Seventy-four patients were excluded due to history of atrial fibrillation and a further 124 patients were lost to follow-up at 1 year. Patient characteristics, intraoperative factors and post-operative outcomes were retrospectively collected. One-year mortality data were collected for 373 patients in the cohort.A total of 497 patients were included, 33 (6.6%) developed POAF within 30 days of surgery. POAF is associated with ischaemic heart disease (24.2 versus 11.6%, P = 0.035), emergency (66.7 versus 34.1%, P = 0.0001) and open procedures (87.9 versus 70.9%, P = 0.036). There is a higher incidence of post-operative complications including pneumonia (24.2 versus 9.1%, P = 0.006), abdominal collection (21.2 versus 9.7%, P = 0.049) and sepsis (21.2 versus 7.5%, P 0.0001). POAF had a higher in-hospital mortality (9.1 versus 2.6%, P = 0.035) and 1-year mortality (33.3 versus 8.8%, P 0.0001).POAF is a common presentation following colorectal surgery and is associated with infective complications, reflecting an inflammatory process. Risk factors for POAF have been clearly identified in the literature; however, further studies need to be conducted on preventative strategies. There is a significantly higher 1-year mortality rate compared with the controls, the aetiology of which has not yet been widely reviewed.

Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple. Visceral malignancies most often arise in the colorectum and endometrium. Because a subset of patients with phenotypic MTS will have germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1, MTS is considered a phenotypic subtype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), in which inherited defects in DNA mismatch repair genes result in microsatellite instability. Pathologists have an important role in the early detection and initial diagnosis of MTS: identification of at-risk individuals allows appropriate screening and surveillance for visceral malignancies, thereby reducing morbidity and mortality. Herein, we describe the clinicopathologic features of MTS.

SUMMARY In recent years, a large body of data has surfaced reporting the therapeutic benefit of botulinum toxin injection in multiple conditions. The aim of this review is: to summarize the highest quality literature pertaining to clinical application of botulinum toxin in neuropathic pain conditions including postherpetic neuralgia, trigeminal neuralgia, diabetic polyneuropathy, post-traumatic neuralgia, carpal tunnel syndrome, complex regional pain syndrome, phantom limb and stump pain, and occipital neuralgia; to provide an overview of the clinical trials using botulinum toxin in adult spasticity; and to assign levels of evidence according to the American Academy of Neurology guidelines. In summary, there is level A evidence for established efficacy in postherpetic neuralgia and adult spasticity; level B evidence for probable efficacy in trigeminal neuralgia and post-traumatic neuralgia; level B evidence for probable lack of efficacy in carpal tunnel syndrome; level C evidence for possible efficacy in diabetic polyneuropathy; and level U (insufficient) evidence in complex regional pain syndrome, phantom limb and stump pain, and occipital neuralgia.