The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease.

Patients with chronic kidney disease (CKD) have an enhanced risk of cardiovascular (CV) morbidity and mortality when compared with age- and gender-matched individuals with normal kidney function. Trimethlyamine N-oxide (TMAO) is a gut-derived amine oxide that has been implicated in the causation of CV diseases. Plasma TMAO is cleared by the kidney, and TMAO levels are elevated in CKD. Experimental studies have identified pathogenic mechanisms by which TMAO may contribute to CV disease through dysregulation of lipid metabolism, enhanced macrophage foam cell formation, and platelet dysfunction. Safe and well-tolerated therapeutic interventions such as pre- and probiotics, which modify the gut microbiome, offer the opportunity for interventional studies. This review examines the pathogenicity of TMAO, its value as a biomarker, and its potential as a therapeutic target in the context of CKD.

Evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs.

BACKGROUND: Cardiovascular side effects associated with cyclooxygenase-2 inhibitor drugs dominate clinical concern. Cyclooxygenase-2 is expressed in the renal medulla where inhibition causes fluid retention and increased blood pressure. However, the mechanisms linking cyclooxygenase-2 inhibition and cardiovascular events are unknown and no biomarkers have been identified. METHODS AND RESULTS: Transcriptome analysis of wild-type and cyclooxygenase-2(-/-) mouse tissues revealed 1 gene altered in the heart and aorta, but >1000 genes altered in the renal medulla, including those regulating the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and monomethyl-l-arginine. Cyclo-oxygenase-2(-/-) mice had increased plasma levels of ADMA and monomethyl-l-arginine and reduced endothelial nitric oxide responses. These genes and methylarginines were not similarly altered in mice lacking prostacyclin receptors. Wild-type mice or human volunteers taking cyclooxygenase-2 inhibitors also showed increased plasma ADMA. Endothelial nitric oxide is cardio-protective, reducing thrombosis and atherosclerosis. Consequently, increased ADMA is associated with cardiovascular disease. Thus, our study identifies ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction with nonsteroidal anti-inflammatory drug usage. CONCLUSIONS: We identify the endogenous endothelial nitric oxide synthase inhibitor ADMA as a biomarker and mechanistic bridge between renal cyclooxygenase-2 inhibition and systemic vascular dysfunction.

Eocene cooling linked to early flow across the Tasmanian Gateway.

The warmest global temperatures of the past 85 million years occurred during a prolonged greenhouse episode known as the Early Eocene Climatic Optimum (52-50 Ma). The Early Eocene Climatic Optimum terminated with a long-term cooling trend that culminated in continental-scale glaciation of Antarctica from 34 Ma onward. Whereas early studies attributed the Eocene transition from greenhouse to icehouse climates to the tectonic opening of Southern Ocean gateways, more recent investigations invoked a dominant role of declining atmospheric greenhouse gas concentrations (e.g., CO2). However, the scarcity of field data has prevented empirical evaluation of these hypotheses. We present marine microfossil and organic geochemical records spanning the early-to-middle Eocene transition from the Wilkes Land Margin, East Antarctica. Dinoflagellate biogeography and sea surface temperature paleothermometry reveal that the earliest throughflow of a westbound Antarctic Counter Current began ~49-50 Ma through a southern opening of the Tasmanian Gateway. This early opening occurs in conjunction with the simultaneous onset of regional surface water and continental cooling (2-4 °C), evidenced by biomarker- and pollen-based paleothermometry. We interpret that the westbound flowing current flow across the Tasmanian Gateway resulted in cooling of Antarctic surface waters and coasts, which was conveyed to global intermediate waters through invigorated deep convection in southern high latitudes. Although atmospheric CO2 forcing alone would provide a more uniform middle Eocene cooling, the opening of the Tasmanian Gateway better explains Southern Ocean surface water and global deep ocean cooling in the apparent absence of (sub-) equatorial cooling.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function.

LGI1 Encephalitis and IgG4-Related Disease: Rare Conditions Collide.

OBJECTIVES: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis and IgG4-related disease (IgG4RD) have traditionally been regarded as 2 distinct disease entities. METHODS: We detail the presentation, investigations, and management of a patient who showed typical signs and symptoms of LGI1 encephalitis and also found to possess pancreatic changes and a serum profile in keeping with IgG4RD. RESULTS: Serum and CSF analyses at presentation showed a significant hyponatraemia (117 mmol/L), elevated IgG4 concentration (1.73 g/L), and the presence of LGI1 antibodies. MRI revealed symmetrical diffuse T2-weighted hyperintensity and mild swelling throughout both medial temporal lobes. CT of the chest, abdomen and pelvis revealed an edematous, bulky pancreas with loss of lobulation, typical for IgG4RD. A glucocorticoid weaning regimen was commenced, facilitated by 2 rituximab infusions, with the patient showing an effective treatment response. HLA testing confirmed the presence of HLA DRB1 and HLA DQB1 risk alleles. DISCUSSION: This case suggests that there may be shared mechanisms between LGI1 encephalitis and IgG4RD, supported by common risk HLA associations and treatment strategies/responses. To our knowledge, this represents the first instance that LGI1 encephalitis and IgG4RD have been reported in the same patient and emphasizes the continued development of our understanding of the wide range of IgG4-mediated conditions.

Gender Differences in Experiences and Expectations of Hemodialysis in a Frail and Seriously Unwell Patient Population.

Introduction: Surprisingly few studies have explored the experiences of seriously unwell people with kidney disease on hemodialysis therapy: we conducted a mixed-methods study to investigate gender differences in illness experience, symptom burden, treatment considerations or expectations in this cohort. Methods: Seriously unwell people on hemodialysis (1-year mortality risk of >20%) at 3 hospital-based units were invited to take part in a structured interview or to complete the same questions independently via a questionnaire. A total of 54 people took part (36 males, 18 females); data analysis was undertaken using a thematic approach. Results: "Desire to keep living" is the most important and basic thought process when starting dialysis. Fear also predominates influencing risk assessment and decision-making. Once fear is managed, there are physical, social, practical and emotional issues to rationalize, but choice only seems possible if shared decision-making is part of the consultation.Gender differences were seen in perceived hopes and expectations of treatment. Males were more likely to prioritize achievement of physical goals, with females prioritizing a wish to feel well. Both genders reported significantly higher symptom scores than their health care provider perceived, however this difference was more marked in females. Dialysis regret existed in >50% of participants and 6 out of 54 (11%) stated that they would have chosen no dialysis at all. Females were more likely to report feeling depressed (P = 0.001). Conclusion: Different genders approach treatment decisions and prioritize treatment expectations differently. Recognizing this will allow personalized care plans to be developed and improve the experiences of seriously unwell people with kidney disease.

Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008-2020).

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC. Materials and methods: Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures. Results: The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%). Conclusion: In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration.

Development of a Novel Rolling-Circle Amplification Technique to Detect Banana streak virus that also Discriminates Between Integrated and Episomal Virus Sequences.

Banana plants are hosts to a large number of Banana streak virus (BSV) species. However, diagnostic methods for BSV are inadequate because of the considerable genetic and serological diversity among BSV isolates and the presence of integrated BSV sequences in some banana cultivars which leads to false positives. In this study, a sequence-nonspecific, rolling-circle amplification (RCA) technique was developed and shown to overcome these limitations for the detection and subsequent characterization of BSV isolates infecting banana. This technique was shown to discriminate between integrated and episomal BSV DNA, specifically detecting the latter in several banana cultivars known to contain episomal or integrated sequences of Banana streak Mysore virus (BSMyV), Banana streak OL virus (BSOLV), and Banana streak GF virus (BSGFV). Using RCA, the presence of BSMyV and BSOLV was confirmed in Australia, while BSOLV, BSGFV, Banana streak Uganda I virus (BSUgIV), Banana streak Uganda L virus (BSUgLV), and Banana streak Uganda M virus (BSUgMV) were detected in Uganda. This is the first confirmed report of episomally-derived BSUglV, BSUgLV, and BSUgMV in Uganda. As well as its ability to detect BSV, RCA was shown to detect two other pararetroviruses, Sugarcane bacilliform virus in sugarcane and Cauliflower mosaic virus in turnip.

Perceptions of Illness Severity, Treatment Goals, and Life Expectancy: The ePISTLE Study.

INTRODUCTION: A better understanding of factors influencing perceived life expectancy (PLE), interactions between patient prognostic beliefs, experiences of illness, and treatment behavior is urgently needed. METHODS: Case-notes at 3 hemodialysis units were screened: patients with ≥20% 1-year mortality risk were included. Patients and their health care professionals (HCPs) were invited to complete a structured interview or mixed-methods questionnaire. Four hundred eleven patient notes were screened. Seventy-seven eligible patients were approached and 51 were included. RESULTS: Patients predicted significantly higher life expectancies than HCPs (P < 0.0001). Documented cognitive impairment, gender, or increasing age did not affect 1- or 5-year PLE. PLE influenced priorities of care: one-fifth of patients who estimated themselves to have >95% 1-year survival preferred "care focusing on relieving pain and discomfort," compared with nearly three-quarters of those reporting a ≤50% chance of 1-year survival. Twenty of 51 (39%) patients believed transplantation was an option for them, despite only 4 being waitlisted at the time of the interview. Patients who thought they were transplant candidates were significantly more confident they would be alive at 1 and 5 years and to want resuscitation attempted. Cognitive impairment had no effect on perceived transplant candidacy. A high symptom burden was present and underrecognized by HCPs. High symptom burden was associated with significantly lower PLE at both 1 and 5 years, increased anxiety/depression scores, and treatment choices more likely to prioritize relief of suffering. CONCLUSION: There is a disparity between patient PLE and those of their HCPs. Severity of symptom burden and beliefs regarding PLE or transplant candidacy affect patient treatment preferences.

Effects of a 1-year randomized controlled trial of resistance training on lower limb bone and muscle structure and function in older men.

SUMMARY: A 1-year randomized controlled trial of resistance training compared with a control group was undertaken in 143 men aged 55-80 years. Although hip bone mineral density, lean body mass, and function increased in both groups, lean body mass and function but not bone density increased more in the resistance group. INTRODUCTION: Previous studies have demonstrated a positive effect of resistance training on bone mineral density (BMD) in postmenopausal women, but the effect in men is unclear. The aim was to examine the effect of a 1-year resistance training program on bone and lean body mass in 143 men aged 55-80 years, randomized to either resistance training or active control. METHODS: Resistance exercises were selected to provide loading at the hips. Measurements were taken at 0, 6, and 12 months for BMD (whole body, hip, and spine), lean body mass, strength, and functional fitness. RESULTS: The intervention showed a significant increase in total hip BMD for both groups at 12 months (active control, 1,014-1,050 mg/cm(2); resistance, 1,045-1,054 mg/cm(2), p < 0.05) with no increased effect of resistance training compared to active control. However, compared to the active control group, the resistance group increased their lean body mass (active control, 0.1 +/- 2.1%; resistance, 1.5 +/- 2.7%, p < 0.05), fitness (active control, 4.6 +/- 11.1%; resistance, 13.0 +/- 13.4%, p < 0.05), and lower limb muscle strength (active control, 14.3 +/- 16.8%; resistance, 39.4 +/- 30.87%, p < 0.05). CONCLUSIONS: In contrast to previous findings in older women, in older men, a resistance training program does not increase hip bone mass more than walking 30 min three times a week.

Memristive GAN in Analog.

Generative Adversarial Network (GAN) requires extensive computing resources making its implementation in edge devices with conventional microprocessor hardware a slow and difficult, if not impossible task. In this paper, we propose to accelerate these intensive neural computations using memristive neural networks in analog domain. The implementation of Analog Memristive Deep Convolutional GAN (AM-DCGAN) using Generator as deconvolutional and Discriminator as convolutional memristive neural network is presented. The system is simulated at circuit level with 1.7 million memristor devices taking into account memristor non-idealities, device and circuit parameters. The design is modular with crossbar arrays having a minimum average power consumption per neural computation of 47nW. The design exclusively uses the principles of neural network dropouts resulting in regularization and lowering the power consumption. The SPICE level simulation of GAN is performed with 0.18 µm CMOS technology and WOx memristive devices with RON = 40 kΩ and ROFF = 250 kΩ, threshold voltage 0.8 V and write voltage at 1.0 V.

Recently published papers: renal support in acute kidney injury - is low dose the new high dose?

Despite 21st century definitions, the management of acute kidney injury remains steadfastly rooted in the 20th century with treatment being principally supportive. Protection from potential causative agents is an essential part of management and to that end protection against contrast-induced nephropathy has received yet more attention. When optimization of volume status, haemodynamic parameters, electrolyte and acid-base disturbances have failed we turn to renal replacement therapy. The time 'bought' on renal support gives a period for renal recovery but although renal replacement therapy is widely employed, many management issues remain unanswered, including the timing, duration and the dose of treatment. In contrast to respiratory support for acute lung injury, for example, there is a paucity of large randomized studies addressing these fundamental issues. We describe some recent studies focusing on these issues with the hope that they may lead to better treatment for our patients.

Plasma lipoprotein beta-amyloid in subjects with Alzheimer's disease or mild cognitive impairment.

BACKGROUND: Plasma amyloid beta-peptide (Abeta) can compromise the blood-brain barrier, contributing to cerebrovascular alterations and amyloid angiopathy in Alzheimer's disease (AD). The objectives of this study were to investigate the distribution of lipoprotein-bound plasma-Abeta isoforms. METHODS: This involved a case-control study of subjects with AD or amnestic mild cognitive impairment (MCI) versus controls. Lipoprotein Abeta distribution was determined in fasted plasma. For assessment of chylomicron homeostasis in the postabsorptive state, subjects were bled 4 h after a low-fat meal. The main outcome measures were plasma lipoprotein Abeta isoform distribution and lipid homeostasis. RESULTS: We found the majority of plasma Abeta to be associated with triglyceride-rich lipoproteins (TRLs) encompassing chylomicrons, VLDL and IDL. For all lipoprotein groups, Abeta1-40 was the predominant isoform, accounting for approximately 50% of the total. Thereafter, equivalent amounts of the isoforms 1-42, 2-40, 1-38, 1-37 and 1-39 were found. Abeta1-37, Abeta1-38 and Abeta2-40 isoforms were significantly enriched within the TRL fraction of AD/MCI subjects and similar trends were observed for isoforms Abeta1-39, Abeta1-40 and Abeta1-42. Lipoprotein-Abeta was inversely associated with plasma total- and LDL cholesterol. AD/MCI subjects were not dyslipidaemic, however, there was evidence of accumulation of chylomicrons in the postabsorptive state. CONCLUSIONS: Our data show that Abeta was found to be associated with plasma lipoproteins, especially those enriched with triglyceride. We find that Abeta may be increased in normolipidaemic AD subjects, commensurate with possible disturbances in postprandial lipoprotein homeostasis.

Fasting and glucose induced thermogenesis in response to three ambient temperatures: a randomized crossover trial in the metabolic syndrome.

BACKGROUND/OBJECTIVES: Cold exposure increases thermogenesis and could improve insulin sensitivity. We hypothesized a blunted response in the metabolic syndrome (MetS). SUBJECTS/METHODS: Twenty older adults 59 ± 10.4 years (with MetS, MetS+, n = 9; without MetS, MetS-, n = 11) completed a randomized crossover design of 3.5 h exposures to 20, 25 and 27 °C on three visits. After an hour's rest at the desired temperature, resting metabolic rate (RMR), respiratory quotient (RQ), forearm to fingertip gradients (FFG), and in the ear temperature (IET) were measured over 30 min. An oral glucose tolerance test followed, and serial measurements were continued for 2 h. Venous blood was sampled for clinical chemistry, irisin, and fibroblast growth factor 21(FGF21). A mixed model ANCOVA adjusted data for age, gender, fat mass, fat-free mass and seasonality. RESULTS: There was a significant MetS×temperature interaction where adjusted RMR was significantly higher in MetS+ compared to MetS- by 12% at 20 °C and by 6% at 25 °C, but similar at 27 °C. FFG increased and IET decreased with decreasing temperature to the same extent in both groups. Fasting irisin and FGF21 did not vary with temperature but the former was significantly higher in MetS-. Adjusted postprandial RQ and insulin to glucose ratios were significantly higher at 20 °C relative to 25 °C. Partial correlation analysis of differences between 27 and 20 °C indicated significant positive relationships between fasting as well as postprandial RQ and the respective changes in irisin and FGF21. CONCLUSIONS: There could be an upward shift of the TNZ in MetS+, but this needs reevaluation.

Identification and molecular characterization of Taro bacilliform virus and Taro bacilliform CH virus from East Africa.

Taro (Colocasia esculenta) and tannia (Xanthosoma sp.) are important root crops cultivated mainly by small-scale farmers in sub-Saharan Africa and the South Pacific. Viruses are known to be one of the most important constraints to production, with infections resulting in severe yield reduction. In 2014 and 2015, surveys were conducted in Ethiopia, Kenya, Tanzania and Uganda to determine the identity of viruses infecting taro in East Africa. Screening of 392 samples collected from the region using degenerate badnavirus primers revealed an incidence of 58-74% among the four countries surveyed, with sequence analysis identifying both Taro bacilliform virus (TaBV) and Taro bacilliform CH virus (TaBCHV). TaBCHV was identified from all four countries while TaBV was identified in all except Ethiopia. Full-length sequences from representative TaBV and TaBCHV isolates showed that the genome organization of TaBV isolates from East Africa was consistent with previous reports while TaBCHV isolates from East Africa were found to encode only four ORFs, distinct from a previous report from China. Phylogenetic analysis showed that all East African TaBV isolates form a single subgroup within known TaBV isolates, while TaBCHV isolates form at least two distinct subgroups. To the authors' knowledge, this is the first report describing the occurrence and genome organization of TaBV and TaBCHV isolates from East Africa and the first full-length sequence of the two viruses from tannia.

Forearm to fingertip skin temperature gradients in the thermoneutral zone were significantly related to resting metabolic rate: potential implications for nutrition research.

BACKGROUND: Resting metabolic rate (RMR) should be measured in the thermoneutral zone (TNZ). Forearm to fingertip skin temperature gradients (FFG) could serve as an objective measure of this pre-condition. SUBJECTS/METHODS: Eighty-six adult Australians were studied at 25 °C in a temperature-controlled chamber. Measurements of overnight fasted RMR, respiratory quotient (RQ) and FFG were complemented by clinical biochemistry. McAuley's Index of insulin sensitivity (McA_ISI) and presence of metabolic syndrome was determined. Physical activity was estimated from the short version of the International Physical Activity Questionnaire. Fat mass (FM) and fat-free mass (FFM) were obtained from dual-energy x-ray absorptiometry. Twenty-nine participants were assessed for changes in RMR (ΔRMR), RQ (ΔRQ) and FFG (ΔFFG) following a 6-month free-living period. Multiple linear regression analyses of RMR and RQ on FFG, and of ΔRMR and ΔRQ on ΔFFG were conducted after controlling for 12 known determinants of energy metabolism. RESULTS: There were wide between-subject variations in unadjusted FFG ranging from -4.25 to +7.8 °C. The final parsimonious model for cross-sectional observations of RMR included age, FM, FFM, McA_ISI and FFG (ß=63 kJ/d (95% confidence interval (CI): 14.2, 112.1, P=0.012)). However, FFG was unrelated to RQ.In the longitudinal cohort, adjusted ΔRMR significantly associated only with ΔFFG (ß=100 kJ/d (95% CI: 10.3, 189.1; P=0.030)), and adjusted ΔRQ associated with ΔFFG (-0.003 (95% CI: -0.005, 0.0002, P=0.038)), age and McA_ISI. CONCLUSIONS: Sizeable between-subject variations in FFG at 25 °C were associated with RMR and RQ. Monitoring FFG may serve as an objective assessment of the TNZ during RMR measurements.

The effect of chronic consumption of red wine polyphenols on vascular function in postmenopausal women.

OBJECTIVE: To elucidate whether the chronic consumption of dealcoholised red wine (DRW) (polyphenol-rich component) and/or red wine (RW) improves vascular function in hypercholesterolaemic postmenopausal women. DESIGN, SUBJECTS AND INTERVENTION: A randomised parallel-arm study. Forty-five hypercholesterolaemic postmenopausal women were randomised into either water, DRW or RW group for 6 weeks following a 4 week washout. Fasting measures of central haemodynamic parameters, arterial wave reflection and endothelial nitric oxide were taken at 0 and 6 weeks. SETTING: Clinic in the School of Public Health, Curtin University. RESULTS: There were no significant between group differences in arterial stiffness as measured by augmentation index (AIx) and augmentation pressure (AP). However, a significant within group decrease in AIx (-9%, P=0.02) and AP (-12%, P=0.02) was observed following DRW consumption. No significant changes were observed in central haemodynamic parameters and endothelial nitric oxide levels following DRW and RW consumption, compared to water. CONCLUSIONS: Neither the chronic consumption of DRW nor RW improved markers of arterial stiffness, compared to control. However, the significant within group improvements in these indices following the consumption of DRW cannot be overlooked and warrant further investigation.

Delirium in critically ill military patients following trauma: A cohort analysis.

Critically ill military trauma patients have been found to have a high incidence of psychological morbidity following their Intensive Care Unit (ICU) experience, including recall of significant auditory and visual hallucinations. It follows that this may be attributable to delirium, which has not been previously described in a young, previously fit population following trauma. The case-notes of 85 male patients (mean age 26 years), admitted to a single UK ICU following military trauma, were retrospectively assessed for delirium using DSM-IV criteria. Of the 993 ICU days assessed, 13.4% were delirium-positive, with just over half of patients (51.8%) experiencing at least one day of delirium. On delirium-positive days, 69.2% received a documented intervention, with the majority of interventions (66.4%) being pharmacological, commonly with a sedative or anti-psychotic. Presence of delirium was significantly associated with severity of injury, assessed by Injury Severity Score (OR 1.037, 95% CI 1.003-1.072, p = 0.031). Duration of ICU stay was significantly increased, from 4 to 8 days (p < 0.005), as was the duration of mechanical ventilation (for the 84.7% of patients who were ventilated) from 7 to 13 days (p < 0.005). Delirium is common in military trauma patients, despite their young age and premorbid fitness. A review of longer-term psychological outcomes should be considered.

Evidence of preferential pairing of chromosomes at meiosis in aneuploid yeast.

Meiotic pairing in homothallic S. cerevisiae was studied by tetrad analysis, using strains that were trisomic or tetrasomic for chromosomes. I. The disomic segregants of these strains produce tetrasomic spore colonies that can be distinguished by their phenotype. Results indicated the existence of preferential pairing and nonrandom assortment of chromosomes at meisosis I. The frequency of crossing over is apparently normal in at least some regions when nonpreferred pairing occurs.