Bayesian emulation and history matching of JUNE.

We analyze JUNE: a detailed model of COVID-19 transmission with high spatial and demographic resolution, developed as part of the RAMP initiative. JUNE requires substantial computational resources to evaluate, making model calibration and general uncertainty analysis extremely challenging. We describe and employ the uncertainty quantification approaches of Bayes linear emulation and history matching to mimic JUNE and to perform a global parameter search, hence identifying regions of parameter space that produce acceptable matches to observed data, and demonstrating the capability of such methods. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study.

OBJECTIVE: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). DESIGN: Prospective population-based study. SETTING: Hospital-based maternity units throughout A&NZ. POPULATION: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. METHODS: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed. MAIN OUTCOME MEASURES: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. RESULTS: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Maori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units. CONCLUSION: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes. TWEETABLE ABSTRACT: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.

Associations between complementary medicine utilisation and the use of contraceptive methods: Results of a national cross-sectional survey.

BACKGROUND AND PURPOSE: This study examines the relationship between the use of complementary medicine (CM) interventions or consultations with CM practitioners and women's choice of contraceptive method. MATERIALS AND METHODS: A secondary analysis of a cross-sectional survey of Australian Women aged 34-39 years from the Australian Longitudinal Study on Women's Health (ALSWH) was conducted. Associations between use of CM and contraception were analysed using Chi-squared tests and multivariate logistic regression. RESULTS: Based on the responses from the included women (n = 7299), women who consulted a naturopath/herbalist were less likely to use implant contraceptives (OR 0.56; 95% confidence interval (CI) 0.33; 0.95). Those consulting a chiropractor (OR 1.54; 95%CI 1.05; 2.25) or an osteopath (OR 2.16; 95% CI 1.32; 3.54) were more likely to use natural contraception. CONCLUSION: There may be a link between women's choice of contraceptive method and their use of CM, in particular, with CM practitioner consultations.

Monitoring and Modeling the Rapid Evolution of Earth's Newest Volcanic Island: Hunga Tonga Hunga Ha'apai (Tonga) Using High Spatial Resolution Satellite Observations.

We have monitored a newly erupted volcanic island in the Kingdom of Tonga, unofficially known as Hunga Tonga Hunga Ha'apai, by means of relatively frequent high spatial resolution (~50 cm) satellite observations. The new ~1.8 km2 island formed as a tuff cone over the course of a month-long hydromagmatic eruption in early 2015 in the Tonga-Kermadec volcanic arc. Such ash-dominated eruptions usually produce fragile subaerial landscapes that wash away rapidly due to marine erosion, as occurred nearby in 2009. Our measured rates of erosion are ~0.00256 km3/year from derived digital topographic models. Preliminary measurements of the topographic expression of the primary tuff cone over ~30 months suggest a lifetime of ~19 years (and potentially up to 42 years). The ability to measure details of a young island's landscape evolution using satellite remote sensing has not previously been possible at these spatial and temporal resolutions.

The characteristics of women who use hypnotherapy for intrapartum pain management: Preliminary insights from a nationally-representative sample of Australian women.

OBJECTIVES: This manuscript presents a preliminary examination of the characteristics of women who choose intrapartum hypnosis for pain management. DESIGN: Cross-sectional analysis of 2445 women (31-36 years) from a sub-study of the Australian Longitudinal Study on Women's Health (ALSWH), employing Fisher exact tests. SETTING: Australia. MAIN OUTCOME MEASURES: Use of intrapartum hypnosis, or hypnobirthing, for pain management during labour and birth. RESULTS: Women using hypnobirthing were more likely to have consulted with an acupuncturist or naturopath, or attended yoga/meditation classes during pregnancy (p<0.0001). Use of CM products such as herbal medicines, aromatherapy oils, homoeopathy, herbal teas or flower essences (p<0.001) was also more common amongst these women. Women choosing hypnotherapy for intrapartum pain management less commonly identified as feeling safer knowing that an obstetrician is providing their care (p<0.001), and were more likely to labour in a birth centre or in a community centre (i.e. at home). CONCLUSIONS: This analysis provides preliminary analysis into an as yet unexamined topic in contemporary maternity health service utilisation. The findings from this analysis may be useful for maternity health professionals and policy makers when responding to the needs of women choosing to use hypnotherapy for intrapartum pain management.

Women's attitudes towards the use of complementary and alternative medicine products during pregnancy.

The aim of this study was to analyse women's attitudes towards the use of complementary and alternative medicine (CAM) products during pregnancy. The study sample was obtained via the Australian Longitudinal Study on Women's Health or ALSWH. A response rate of 79.2% (n = 1,835) was attained. Women who use herbal medicines (34.5%, n = 588) view CAM as a preventative measure, are looking for something holistic and are concerned about evidence of clinical efficacy when considering the use of these products during pregnancy. Women who use aromatherapy (17.4%, n = 319) and homoeopathy (13.3%, n = 244) want more personal control over their body and are concerned more about their own personal experience of the efficacy of CAM than clinical evidence of efficacy. As CAM use in pregnancy appears to be increasingly commonplace, insights into women's attitudes towards CAM are valuable for maternity healthcare providers.

Safety and adequacy of percutaneous biopsies in pediatric orthotopic kidney transplantation.

BACKGROUND: The gold standard for investigating the cause of renal graft dysfunction is renal biopsy. However, as this procedure is invasive and has inherent risks, its safety must be established. OBJECTIVE: To determine the safety of percutaneous renal biopsy in pediatric orthotopic renal transplantation. METHODS: Percutaneous renal biopsies performed on pediatric orthotopic renal transplants in a single center between 1987 and 2010 were studied. Biopsy specimen adequacy and post-procedure complications were reviewed by prospectively collected data. RESULTS: A total of 54 ultrasound "real-time" guided biopsies in 25 patients were performed. Minimum specimen adequacy was achieved in 98% of biopsy specimens. No major complications were identified; 6% of patients developed minor complications-e.g., grade 3 macroscopic hematuria that did not require intervention. CONCLUSION: Percutaneous renal biopsies using "real-time" ultrasound guidance on pediatric orthotopic kidney transplants is safe.

Risk factors for peri-operative stroke complicating carotid endarterectomy: selective analysis of a prospective audit of 1000 consecutive operations.

BACKGROUND: The aim of the present study was to investigate the role of potential clinical risk factors in the causation of peri-operative stroke associated with carotid endarterectomy. With the change in carotid endarterectomy practice from the use of a shunt to high-dose thiopental for cerebral protection (a previously undocumented method), it was essential to identify accurately the causes of all perioperative strokes. METHODS: A prospective audit was undertaken of 1000 carotid endarterectomies in which the causes and pathology of all peri-operative strokes were documented. The roles of advanced age, female gender, hypertension, previous stroke, contralateral carotid stenosis >70%, and contralateral carotid occlusion as potential causes of peri-operative stroke were defined. Results were statistically analysed using odds ratio and Fisher's exact test. RESULTS: None of the potential risk factors was statistically significant for peri-operative stroke. Female gender was associated with a significant risk of peri-operative stroke due to operative site thrombosis. Complications at the endarterectomy site were the commonest cause of stroke. CONCLUSIONS: Prospective audit is a useful tool for identifying causes of peri-operative stroke and indicating the need for modifications to surgical clinical management which might improve outcomes for carotid endarterectomy.

Test conditions influence the response to a drug challenge in rodents.

These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.

Hyperbaric oxygenation treatment of acute paraplegia after resection of a thoracoabdominal aortic aneurysm.

Acute spinal cord ischemic injury after resection of thoracoabdominal aneurysm remains a relatively common and potentially devastating complication. The complete resolution of postoperative paraplegia after resection of a type II thoracoabdominal aneurysm, after treatment with hyperbaric oxygenation, is reported.

Hemodynamic ischemic stroke during carotid endarterectomy: an appraisal of risk and cerebral protection.

PURPOSE: The purpose of this study was to validate the commonly accepted indicators of risk of ischemic stroke that indicate the necessity for cerebral protection during carotid endarterectomy (CEA), and to examine the efficacy of high-dose thiopentone sodium (thiopental) as a cerebral protection method in patients who are at high risk of intraoperative ischemic stroke. METHOD: In a prospective study of 37 CEAs performed for symptomatic stenosis > 70%, functional and clinical indicators of risk of ischemic stroke during carotid cross-clamping were identified. Functional indicators of risk were the development of ischemic electro-encephalogram (EEG) changes and stump pressure < 25 mm Hg. Clinical indicators of risk were previous ischemic hemispheric stroke and severe bilateral disease. These indicators were correlated in all patients, some of whom had two or three coexisting indicators of risk. The EEG and stump pressure were monitored continuously during carotid occlusion in all operations. Carotid occlusion times were recorded. Intraluminal shunting was eliminated in favor of high-dose thiopental cerebral protection in all patients. Neurologic outcome was deemed to measure the efficacy of thiopental protection in patients who are identified to be at risk and, hence, in need of cerebral protection. The validity of the indicators used to identify risk of ischemic stroke during CEA was assessed. RESULTS: The absolute stroke risk was found to be 29.7% for the whole group (37 patients) and 57.9% in 19 patients who had commonly accepted indications for protective shunting. The correlation of ischemic EEG changes with stump pressure < 25 mm Hg was only 27.3%, whereas the expected correlation based on well-documented reports in the literature was 100%. The lack of correlation may have been related to the prevention of ischemic EEG changes by thiopental. There were no neurologic deficits in the series. CONCLUSIONS: The absence of neurologic deficit in the study indicated that thiopental protection was effective in preventing ischemic stroke in high-risk patients and safely replaced intraluminal shunting.

A mobile lesion in the carotid artery.

The case of a 68 year old woman with a sudden onset of visual loss in the left eye is reported. Carotid duplex scanning revealed a 50-75% stenosis of the left internal carotid artery, with a floating tail of clot extending into the lumen of the artery. Emergency carotid endarterectomy, removing the plaque with the attached thrombus, was performed.

Carotid endarterectomy without a shunt for symptomatic lesions associated with contralateral severe stenosis or occlusion.

PURPOSE: The purpose of this study was to assess the adequacy of thiopental protection against ischemic cerebral damage in patients undergoing carotid endarterectomy for symptomatic stenosis greater than 70% in association with contralateral stenosis greater than 70% or contralateral occlusion. METHODS: All patients (n=259) with severe bilateral carotid disease who underwent carotid endarterectomy for symptomatic stenosis greater than 70% were extracted from the database of an ongoing prospective carotid surgery study. Large-dose thiopental sodium without shunting was used for cerebral protection during endarterectomy. Asymmetric electroencephalogram changes during the operation, carotid occlusion time, stroke onset, and neuropathologic outcomes were analyzed. RESULTS: Three contralateral strokes occurred in the series, producing a cerebral morbidity/mortality rate of 1.2% (major 0.4%, minor 0.8%). Transient morbidity was 1.9% made of two reversible ischemic neurologic deficits and three transient ischemic attacks. New asymmetric electroencephalography changes were seen in 49 (19% patients, one of whom had transient deficit. Average occlusion time was 35 minutes. All strokes occurred within 24 hours of the procedure. Patients with previous stroke and and systemic hypertension seemed at greatest risk, and the contralateral hemisphere was the area at greatest risk. All transient deficits were ipsilateral and related to technical complications rather failed protection. CONCLUSIONS: Thiopental cerebral protection eliminates strokes caused by complications of shunting, prevents ischemic stroke during carotid occlusion for periods up to 67 minutes (average 35 minutes), allows meticulous management of the operative site, may modify or minimize clinical neurologic deficit, and in our experience has rendered intraluminal shunting obsolete.

Primary access surgery for long-term haemodialysis.

This paper assessed the efficacy of arterio-venous fistulae, vein grafts, and synthetic grafts for long-term haemodialysis. Over a selected 10 year period, 486 primary access sites were established and 182 revisions were necessary. Access procedures were assessed for primary survival, the success or otherwise of revision surgery, and long-term efficacy for haemodialysis. Significant differences were shown for long-term survival of fistulae over vein grafts and synthetic grafts. Successful revision surgery favoured fistulae over synthetic grafts. Arterio-venous fistulae offered the best prospect for effective long-term dialysis. Revision surgery with continued dialysis using the primary-access site was largely unsuccessful, secondary access reconstruction being required in 78.2% of all failures.

Thiopental sodium cerebral protection during carotid endarterectomy: perioperative disease and death.

PURPOSE: This study reports our experience with thiopental sodium (Pentothal) cerebral protection, without intraluminal shunting, during carotid endarterectomy. Only those complications that occurred during surgery or within 30 days of operation have been addressed. METHOD: A prospective, unselected, consecutive series of 621 carotid endarterectomies was done during a 7-year period, with electroencephalography-monitored, high-dose Pentothal for cerebral protection. RESULTS: Five ischemic strokes (0.8%), completion of two strokes-in-evolution (0.3%) and four strokes caused by cerebral hemorrhage (0.6%) occurred in 11 patients in the perioperative (30-day) period, for a combined cerebral morbidity-mortality rate of 1.7%. Four reversible ischemic neurologic deficits (0.6%) and two transient ischemic attacks (0.3%) in six patients produced a transient deficit rate of 0.9%. Symptomatic coronary artery disease coexisted in 37% of the patients but resulted in only five acute myocardial infarctions (0.7%), one of which was fatal (0.1%). Other perioperative complications in 10 patients (1.5%) were associated with the operative procedure. There were no complications directly attributable to the high-dose Pentothal. Prospective data collection has allowed definition of the disease and cause of all cerebral complications. CONCLUSION: The complications in this series have been related to surgical and clinical management problems rather than failure of cerebral protection. Cerebral protection with high-dose Pentothal under electroencephalographic control has been effective and complication free.

Aortic aneurysm surgery in the presence of a horseshoe kidney.

A review of three cases of aortic aneurysm in association with a horseshoe kidney is presented. Both the transperitoneal and retroperitoneal approaches to the aneurysm are detailed and the relative advantages and disadvantages outlined. The conventional approach of transection of the renal isthmus is not recommended because of the possibility of damage to the collecting system of the horseshoe kidney. The place of specialized investigations is outlined.

Superior mesenteric vein thrombosis.

Superior mesenteric venous occlusion may be difficult to recognize, but is important as it carries a better prognosis than superior mesenteric arterial occlusion, and may be amenable to surgical treatment. Three successful cases treated by thrombectomy have appeared in the literature. A case of successful superior mesenteric vein thrombectomy with bowel resection is reported.

Clinical features of vascular insufficiency in the limbs.

Drugs (nicotine, beta blockers) can exacerbate symptoms of vascular insufficiency. Vasodilators and anticoagulants have no place in the treatment of chronic insufficiency. Analgesics rarely, if ever, relieve ischaemic pain at rest. Ischaemic pain at rest and gangrene are absolute indications for surgical restoration of the circulation. Spasm is never the determining factor in acute insufficiency associated with trauma. Surgical restoration of circulation is essential in most cases of acute insufficiency. The knee joint should be preserved if possible in lower limb amputation, even if proximal vascular reconstruction is necessary. Surgery should not be denied on the basis of age or infirmity. Restoration of normal circulation in the limb is the best treatment for vascular insufficiency. Acute or chronic vascular insufficiency is eminently correctable in most cases. Advances in diagnosis, patient selection, anaesthesia, operative surgery and rehabilitation have rendered reconstructive procedures safe and successful. Early diagnosis and referral to a vascular unit with modern facilities offers a greater chance of salvage of life and limb than that possible in earlier decades. Many patients return to an independent life free of pain and requiring minimal ongoing care.