Enigmatic fossil plants with three-dimensional, arborescent-growth architecture from the earliest Carboniferous of New Brunswick, Canada.

The evolution of arborescence in Devonian plants, followed by their architectural radiation in the Carboniferous, is a transition fundamental to Earth-system processes and ecological development. However, this evolutionary transition in trees is based on preserved trunks, of which only a few known specimens possess crowns. We describe Mississippian-aged (Tournaisian) trees with a unique three-dimensional crown morphology from New Brunswick, Canada. The trees were preserved by earthquake-induced, catastrophic burial of lake-margin vegetation. The tree architecture consists of an unbranched, 16-cm-diameter trunk with compound leaves arranged in spirals of ∼13 and compressed into ∼14 cm of vertical trunk length. Compound leaves in the upper ∼0.75 m of the trunk measure >1.75 m in length and preserve alternately arranged secondary laterals beginning at 0.5 m from the trunk; the area below the trunk bears only persistent leaf bases. The principal specimen lacks either apical or basal sections, although an apex is preserved in another. Apically, the leaves become less relaxed toward horizontal and are borne straight at an acute angle at the crown. The compact leaf organization and leaf length created a crown volume of >20-30 m3. This growth strategy likely maximized light interception and reduced resource competition from groundcover. From their growth morphology, canopy size, and volume, we propose that these fossils represent the earliest evidence of arborescent subcanopy-tiering. Moreover, although systematically unresolved, this specimen shows that Early Carboniferous vegetation was more complex than realized, signaling that it was a time of experimental, possibly transitional and varied, growth architectures.

Comparing preoperative fasting and ultrasound-measured intravascular volume status in elective surgery, enhanced recovery patients versus inpatient, urgent surgery patients and the ability of IVC collapsibility to predict post-induction hypotension.

Hypotension following induction of general anaesthesia has been shown to result in increased complications and mortality postoperatively. Patients admitted to the hospital undergoing urgent surgery are often fasted from fluids for significant periods compared to elective patients subject to Enhanced Recovery After Surgery protocols despite guidelines stating that a two-hour fast is sufficient. The aim of this prospective, observational study was to compare fasting times and intravascular volume status between elective surgery patients subject to enhanced recovery protocols and inpatient, urgent surgery patients and to assess differences in the incidence of post-induction hypotension. Fasting data was obtained by questionnaire in the preoperative area in addition to inferior vena cava collapsibility index, a non-invasive measure of intravascular volume. Blood pressure readings and drug administration for the ten minutes following induction were obtained from patients' charts. Inpatients undergoing urgent surgery were fasted significantly longer than enhanced recovery patients and had lower intravascular volume. However, no difference was found in the incidence of post-induction hypotension.

Venous Excess Ultrasound (VExUS Grading to Assess Perioperative Fluid Status for Noncardiac Surgeries: a Prospective Observational Pilot Study.

Objectives: Perioperative fluid administration impacts the rate of complications following surgery. VExUS grading system is a standardized point of care ultrasound (POCUS)-based, comprehensive method to assess volume status. VExUS could serve as a tool to guide fluid management, if validated perioperatively. The primary aim was to assess the success rate of obtaining required windows for VExUS grading , as well as the feasibility within a perioperative setting among noncardiac surgery. Further, this study describes the incidence of perioperative venous congestion and associations with 30-day postoperative complications. Methods: This observational study was conducted in non-critically ill adults undergoing noncardiac surgery. Patients were scanned preoperatively, in the post anesthesia care unit (PACU), and 24 hours postoperatively for venous congestion. Researchers retrospectively captured 30-day complications for multivariate analyses. Results: The cohort included 69 participants. Ninety-one percent of scans over all timepoints were successfully completed. Pre-operatively, 57 (83%) scans were Grade 0, and 11 (16%) were Grade 1. Venous congestion was observed in 29 (44%) patients in the PACU (n=66). 22 (33%) patients were Grade 1, while 7 (11%) were Grade 2. At 24 hours (n=63), 31 patients (49%) had venous congestion: 20 (32%) Grade 1 and 11 (17%) Grade 2. Of the pre-operative Grade 0, 28 (50%) had at least one postoperative scan with venous congestion. No patients were Grade 3 at any timepoint. The 30-day complication rate was 32% (n=22). Eleven (16%) patients developed acute kidney injury (AKI). There was no statistically significant association between VExUS grading and all-cause complications or AKI. Conclusion: This study demonstrates that perioperative VExUS scoring is a feasible tool among a variety of noncardiac surgeries. We highlight that venous congestion is common and increases postoperatively within non-ICU populations. Larger studies are needed to assess the relationship between VExUS grading and postoperative complications.

Perioperative colloid choice and bleeding in patients undergoing musculoskeletal surgery: An observational administrative database study.

BACKGROUND: The synthetic colloid hydroxyethyl starch (HES) received a black box warning, issued by the US Food and Drug Administration (FDA) in June 2013, in patients with sepsis, due to increased risk of bleeding, renal injury, and death. Risks of HES in populations undergoing noncardiac surgery are unclear. Here, we examine the association of colloid choice - human-derived albumin versus HES - with bleeding in musculoskeletal surgery. METHODS: Inpatient musculoskeletal surgical patients who received colloids on the day of surgery were included during a time period before the FDA warning on HES using the Premier Healthcare database. The exposure was type of colloids administered on the day of surgery: HES versus albumin. The primary outcome was major perioperative bleeding, measured on the 1st postoperative day through hospital discharge. The secondary outcomes included acute renal failure and postoperative length of stay >75th percentile. RESULTS: We identified 41,211 patients who received albumin (n = 12,803) and HES (n = 28,408) on the day of surgery. The propensity-weighted multivariable analysis demonstrated a reduced risk of major perioperative bleeding on the day after surgery following treatment with albumin versus HES (relative risk: 0.89 [95% confidence interval, 0.84-0.93]). No significant differences were observed in the secondary outcomes. CONCLUSION: When compared with albumin, treatment with HES on the day of musculoskeletal surgery was associated with an increased risk of major perioperative bleeding on subsequent days. Given that HES continues to be used as a colloid in multiple patient populations worldwide, further studies examining the safety of HES versus albumin solutions are needed.

Bleeding After Musculoskeletal Surgery in Hospitals That Switched From Hydroxyethyl Starch to Albumin Following a Food and Drug Administration Warning.

BACKGROUND: While US Food and Drug Administration (FDA) black box warnings are common, their impact on perioperative outcomes is unclear. Hydroxyethyl starch (HES) is associated with increased bleeding and kidney injury in patients with sepsis, leading to an FDA black box warning in 2013. Among patients undergoing musculoskeletal surgery in a subset of hospitals where colloid use changed from HES to albumin following the FDA warning, we examined the rate of major perioperative bleeding post- versus pre-FDA warning. METHODS: The authors of this article used a retrospective, quasi-experimental, repeated cross-sectional, interrupted time series study of patients undergoing musculoskeletal surgery in hospitals within the Premier Healthcare Database, in the year before and year after the 2013 FDA black box warning. We examined patients in 23 "switcher" hospitals (where the percentage of colloid recipients receiving HES exceeded 50% before the FDA warning and decreased by at least 25% in absolute terms after the FDA warning) and patients in 279 "nonswitcher" hospitals. Among patients having surgery in "switcher" and "nonswitcher" hospitals, we determined monthly rates of major perioperative bleeding during the 12 months after the FDA warning, compared to 12 months before the FDA warning. Among patients who received surgery in "switcher" hospitals, we conducted a propensity-weighted segmented regression analysis assessing differences-in-differences (DID), using patients in "nonswitcher" hospitals as a control group. RESULTS: Among 3078 patients treated at "switcher" hospitals (1892 patients treated pre-FDA warning versus 1186 patients treated post-FDA warning), demographic and clinical characteristics were well-balanced. Two hundred fifty-one (13.3%) received albumin pre-FDA warning, and 900 (75.9%) received albumin post-FDA warning. Among patients undergoing surgery in "switcher" hospitals during the pre-FDA warning period, 282 of 1892 (14.9%) experienced major bleeding during the hospitalization, compared to 149 of 1186 (12.6%) following the warning. In segmented regression, the adjusted ratio of slopes for major perioperative bleeding post- versus pre-FDA warning was 0.98 (95% confidence interval [CI], 0.93-1.04). In the DID estimate using "nonswitcher" hospitals as a control group, the ratio of ratios was 0.93 (95% CI, 0.46-1.86), indicating no significant difference. CONCLUSIONS: We identified a subset of hospitals where colloid use for musculoskeletal surgery changed following a 2013 FDA black box warning regarding HES use in sepsis. Among patients undergoing musculoskeletal surgery at these "switcher" hospitals, there was no significant decrease in the rate of major perioperative bleeding following the warning, possibly due to incomplete practice change. Evaluation of the impact of systemic changes in health care may contribute to the understanding of patient outcomes in perioperative medicine.

Causal inference in perioperative medicine observational research: part 1, a graphical introduction.

Graphical models have emerged as a tool to map out the interplay between multiple measured and unmeasured variables, and can help strengthen the case for a causal association between exposures and outcomes in observational studies. In Part 1 of this methods series, we will introduce the reader to graphical models for causal inference in perioperative medicine, and set the framework for Part 2 of the series involving advanced methods for causal inference.

Causal inference in perioperative medicine observational research: part 2, advanced methods.

Although RCTs represent the gold standard in clinical research, most clinical questions cannot be answered using this technique, because of ethical considerations, time, and cost. The goal of observational research in clinical medicine is to gain insight into the relationship between a clinical exposure and patient outcome, in the absence of evidence from RCTs. Observational research offers additional benefit when compared with data from RCTs: the conclusions are often more generalisable to a heterogenous population, which may be of greater value to everyday clinical practice. In Part 2 of this methods series, we will introduce the reader to several advanced methods for supporting the case for causality between an exposure and outcome, including: mediation analysis, natural experiments, and joint effects methods.

Seasonality and schizophrenia: a comprehensive overview of the seasonal pattern of hospital admissions and potential drivers.

Schizophrenia is a severe neuropsychiatric disorder with heterogeneous aetiology mostly affecting younger people and causing immense disability. Seasonal patterns may be observed in schizophrenia hospital admissions with possible association with changing climatic parameters and socio-demographic characteristics. This study critically reviewed studies that have assessed seasonal variations of hospital admissions for schizophrenia and/or explored an association with climate parameters and/or other potential factors. Following PRISMA guidelines, a systematic literature search was conducted using electronic databases (e.g. MEDLINE, Science Direct, PsycINFO, Pub Med) from inception to February 29, 2020. Thirty five papers were identified, of which only six (17.1%) examined evidence for a seasonal pattern or monthly excess of hospital admissions and the remaining twenty nine (82.9%) assessed climatic and socio-demographic attributes relating to the seasonal pattern or increased hospitalisation for schizophrenia. While most studies reported a summer peak in hospital admission rates, other studies reported a winter peak. Most of the evidence indicated that higher temperatures (> 28 °C) were positively correlated with schizophrenia admission rates. The individual effects of other climatic parameters (e.g. relative humidity, rainfall, atmospheric pressure, sunlight) were less frequently assessed. Males, people of 21-60 years old, and those married were more vulnerable to climatic variability specifically to higher temperatures. Further studies using large sample sizes, analysis of a wide range of interacting environmental variables and sophisticated statistical approaches are needed to better understand the underlying mechanisms involved. This will also provide more reliable statistical evidence that will help in the prevention and better management of cases.

Association of Schizophrenia Risk With Disordered Niacin Metabolism in an Indian Genome-wide Association Study.

Importance: Genome-wide association studies (GWASs) in European populations have identified more than 100 schizophrenia-associated loci. A schizophrenia GWAS in a unique Indian population offers novel findings. Objective: To discover and functionally evaluate genetic loci for schizophrenia in a GWAS of a unique Indian population. Design, Setting, and Participants: This GWAS included a sample of affected individuals, family members, and unrelated cases and controls. Three thousand ninety-two individuals were recruited and diagnostically ascertained via medical records, hospitals, clinics, and clinical networks in Chennai and surrounding regions. Affected participants fulfilled DSM-IV diagnostic criteria for schizophrenia. Unrelated control participants had no personal or family history of psychotic disorder. Recruitment, genotyping, and analysis occurred in consecutive phases beginning January 1, 2001. Recruitment was completed on February 28, 2018, and genotyping and analysis are ongoing. Main Outcomes and Measures: Associations of single-nucleotide polymorphisms and gene expression with schizophrenia. Results: The study population included 1321 participants with schizophrenia, 885 family controls, and 886 unrelated controls. Among participants with schizophrenia, mean (SD) age was 39.1 (11.4) years, and 52.7% were male. This sample demonstrated uniform ethnicity, a degree of inbreeding, and negligible rates of substance abuse. A novel genome-wide significant association was observed between schizophrenia and a chromosome 8q24.3 locus (rs10866912, allele A; odds ratio [OR], 1.27 [95% CI, 1.17-1.38]; P = 4.35 × 10-8) that attracted support in the schizophrenia Psychiatric Genomics Consortium 2 data (rs10866912, allele A; OR, 1.04 [95% CI, 1.02-1.06]; P = 7.56 × 10-4). This locus has undergone natural selection, with the risk allele A declining in frequency from India (approximately 72%) to Europe (approximately 43%). rs10866912 directly modifies the abundance of the nicotinate phosphoribosyltransferase gene (NAPRT1) transcript in brain cortex (normalized effect size, 0.79; 95% CI, 0.6-1.0; P = 5.8 × 10-13). NAPRT1 encodes a key enzyme for niacin metabolism. In Indian lymphoblastoid cell lines, (risk) allele A of rs10866912 was associated with NAPRT1 downregulation (AA: 0.74, n = 21; CC: 1.56, n = 17; P = .004). Preliminary zebrafish data further suggest that partial loss of function of NAPRT1 leads to abnormal brain development. Conclusions and Relevance: Bioinformatic analyses and cellular and zebrafish gene expression studies implicate NAPRT1 as a novel susceptibility gene. Given this gene's role in niacin metabolism and the evidence for niacin deficiency provoking schizophrenialike symptoms in neuropsychiatric diseases such as pellagra and Hartnup disease, these results suggest that the rs10866912 genotype and niacin status may have implications for schizophrenia susceptibility and treatment.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study.

OBJECTIVE: To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. DESIGN: Hospital based registry study. SETTING: Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. PARTICIPANTS: 69,265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. INTERVENTIONS: Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH2O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH2O. MAIN OUTCOME MEASURE: Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. RESULTS: Of the 69,265 enrolled patients 34,800 (50.2%) received protective ventilation and 34,465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH2O and median plateau pressures of 16 cmH2O or less were associated with the lowest risk of postoperative respiratory complications. CONCLUSIONS: Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH2O and a plateau pressure of 16 cmH2O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.

Dose-dependent Association between Intermediate-acting Neuromuscular-blocking Agents and Postoperative Respiratory Complications.

BACKGROUND: Duration of action increases with repeated administration of neuromuscular-blocking agents, and intraoperative use of high doses of neuromuscular-blocking agent may affect respiratory safety. METHODS: In a hospital-based registry study on 48,499 patients who received intermediate-acting neuromuscular-blocking agents, the authors tested the primary hypothesis that neuromuscular-blocking agents are dose dependently associated with the risk of postoperative respiratory complications. In the secondary analysis, the authors evaluated the association between neostigmine dose given for reversal of neuromuscular-blocking agents and respiratory complications. Post hoc, the authors evaluated the effects of appropriate neostigmine reversal (neostigmine ≤ 60 µg/kg after recovery of train-of-four count of 2) on respiratory complications. The authors controlled for patient-, anesthesia-, and surgical complexity-related risk factors. RESULTS: High doses of neuromuscular-blocking agents were associated with an increased risk of postoperative respiratory complications (n = 644) compared with low doses (n = 205) (odds ratio [OR], 1.28; 95% CI, 1.04 to 1.57). Neostigmine was associated with a dose-dependent increase in the risk of postoperative respiratory complications (OR, 1.51; 95% CI, 1.25 to 1.83). Post hoc analysis revealed that appropriate neostigmine reversal eliminated the dose-dependent association between neuromuscular-blocking agents and respiratory complications (for neuromuscular-blocking agent effects with appropriate reversal: OR, 0.98; 95% CI, 0.63 to 1.52). CONCLUSIONS: The use of neuromuscular-blocking agents was dose dependently associated with increased risk of postoperative respiratory complications. Neostigmine reversal was also associated with a dose-dependent increase in the risk of respiratory complications. However, the exploratory data analysis suggests that the proper use of neostigmine guided by neuromuscular transmission monitoring results can help eliminate postoperative respiratory complications associated with the use of neuromuscular-blocking agents.

Comparing schizophrenia symptoms in the Iban of Sarawak with other populations to elucidate clinical heterogeneity.

INTRODUCTION: The symptom profile of schizophrenia can vary between ethnic groups. We explored selected symptom variables previously reported to be characteristic of schizophrenia in the Iban of Sarawak in transethnic populations from Australia, India, and Sarawak, Malaysia. We tested site differences to confirm previous research, and to explore implications of differences across populations for future investigations. METHODS: We recruited schizophrenia samples in Australia (n = 609), India (n = 310) and Sarawak (n = 205) primarily for the purposes of genetic studies. We analyzed seven identified variables and their relationship to site using logistic regression, including: global delusions, bizarre delusions, thought broadcast/insertion/withdrawal delusions, global hallucinations, auditory hallucinations, disorganized behavior, and prodromal duration. RESULTS: We identified a distinct symptom profile in our Sarawak sample. Specifically, the Iban exhibit: low frequency of thought broadcast/insertion/withdrawal delusions, high frequency of auditory hallucinations and disorganized behavior, with a comparatively short prodrome when compared with Australian and Indian populations. DISCUSSION: Understanding between-site variation in symptom profile may complement future transethnic genetic studies, and provide important clues as to the nature of differing schizophrenia expression across ethnically distinct groups. A comprehensive approach to subtyping schizophrenia is warranted, utilizing comprehensively ascertained transethnic samples to inform both schizophrenia genetics and nosology.

Residual Paralysis: Does it Influence Outcome After Ambulatory Surgery?

Neuromuscular blocking agents are used to facilitate tracheal intubation in patients undergoing ambulatory surgery. The use of high-dose neuromuscular blocking agents to achieve muscle paralysis throughout the case carries an increased risk of residual post-operative neuromuscular blockade, which is associated with increased respiratory morbidity. Visually monitoring the train-of-four (TOF) fade is not sensitive enough to detect a TOF fade between 0.4 and 0.9. A ratio <0.9 indicates inadequate recovery. Quantitative neuromuscular transmission monitoring (e.g., acceleromyography) should be used to exclude residual neuromuscular blockade at the end of the case. Residual neuromuscular blockade needs to be reversed with neostigmine, but it's use must be guided by TOF monitoring results since deep block cannot be reversed, and neostigmine administration after complete recovery of the TOF-ratio can induce muscle weakness. The development and use of new selectively binding reversal agents (sugammadex and calabadion) warrants reevaluation of this area of clinical practice.

DSM-IV "criterion A" schizophrenia symptoms across ethnically different populations: evidence for differing psychotic symptom content or structural organization?

There is significant variation in the expression of schizophrenia across ethnically different populations, and the optimal structural and diagnostic representation of schizophrenia are contested. We contrasted both lifetime frequencies of DSM-IV criterion A (the core symptom criterion of the internationally recognized DSM classification system) symptoms and types/content of delusions and hallucinations in transethnic schizophrenia populations from Australia (n = 776), India (n = 504) and Sarawak, Malaysia (n = 259), to elucidate clinical heterogeneity. Differences in both criterion A symptom composition and symptom content were apparent. Indian individuals with schizophrenia reported negative symptoms more frequently than other sites, whereas individuals from Sarawak reported disorganized symptoms more frequently. Delusions of control and thought broadcast, insertion, or withdrawal were less frequent in Sarawak than Australia. Curiously, a subgroup of 20 Indian individuals with schizophrenia reported no lifetime delusions or hallucinations. These findings potentially challenge the long-held view in psychiatry that schizophrenia is fundamentally similar across cultural groups, with differences in only the content of psychotic symptoms, but equivalence in structural form.

Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia.

Schizophrenia is a severe debilitating brain disorder with a poorly understood aetiology. Among the diverse aetiological clues lies evidence for immune abnormalities in some individuals. The aim of this study was to investigate the frequency and specificity of autoantibodies directed against the brain in people with schizophrenia. Sera were screened for reactivity against human brain tissue (hippocampus and prefrontal cortex). Neuronal cell body and filamentous patterns of brain tissue staining were observed significantly more frequently in sera from schizophrenia patients (n=30) compared to controls (n=24). Sera that showed a neuronal cell body pattern of staining on hippocampus reacted strongly to an extracellular epitope of the M1 muscarinic acetylcholine receptor (m1AChR) in ELISA. Both cell body staining and elevated m1AChR reactivity correlated with higher symptom scores for poverty of speech. Sera showing a filamentous staining pattern predominantly targeted microfilaments, intermediate filaments or neurofilaments, particularly neurofilament medium (NFM), which is a dopamine receptor interacting protein. By ELISA, there was strongly elevated reactivity against NFM in a subset (15%) of schizophrenia patients (n=101) compared to healthy controls (n=55) or patients with multiple sclerosis (n=32). These results support the hypothesis that neurotransmitter receptors or molecules involved in regulation of neurotransmission are targets of autoantibodies in some people with schizophrenia.

Refining clinical phenotypes by contrasting ethnically different populations with schizophrenia from Australia, India and Sarawak.

We contrasted demographic and clinical characteristics in transethnic schizophrenia populations from Australia (n=821), India (n=520) and Sarawak, Malaysia (n=298) and proposed cultural explanations for identified site differences. From these we aimed to identify candidate variables free from significant cultural confounding that are hence suitable for inclusion in genetic analyses. We observed five phenomena: (1) more individuals were living alone in Australia than India or Sarawak; (2) drug use was lower in India than Australia or Sarawak; (3) duration of untreated psychosis (DUP) was longer in India than Australia or Sarawak; (4) the rate of schizoaffective disorder was lower in India than Australia or Sarawak; and (5) age at psychosis onset (AAO) was older in Sarawak than Australia or India. We suggest that site differences for living arrangements, drug use and DUP are culturally confounded. The schizoaffective site difference likely results from measurement bias. The AAO site difference, however, has no obvious cultural or measurement bias explanation. Therefore, this may be an ideal candidate for use in genetic studies, given that genetic variants affecting AAO have already been proposed.