PATIENT DOSE ASSESSMENT AND OPTIMISATION OF PELVIC RADIOGRAPHY WITH COMPUTED RADIOGRAPHY SYSTEMS.

Digital radiography systems can reduce radiation dose, this capability was harnessed to explore dose and image quality (IQ) optimisation strategies. Entrance surface dose (ESD), effective dose (ED) and organ doses were determined by the indirect method for patients undergoing pelvic anteroposterior X-ray examinations with computed radiography systems. The IQ of patients' radiographs was assessed in terms of signal-to-noise ratio (SNR). An anthropomorphic phantom was exposed with varying tube potential (kVp), tube current-time product (mAs), and focus-to-detector distance (FDD) to determine phantom-entrance dose for the optimisation studies. SNR of each phantom radiograph was determined. Patients' mean ESD of 2.38 ± 0.60 mGy, ED of 0.25 ± 0.07 mSv and SNR of 8.5 ± 2.2 were obtained. After optimisation, entrance dose was reduced by 29.2% with 5 cm increment in FDD, and 5 kVp reduction in tube potential. kVp and/or mAs reduction with an increment in FDD reduced entrance dose without adversely compromising radiographic-IQ.

Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis.

Cleft palate is a common birth defect that frequently occurs in human congenital malformations caused by mutations in components of the Sonic Hedgehog (S HH) signaling cascade. Shh is expressed in dynamic, spatiotemporal domains within epithelial rugae and plays a key role in driving epithelial-mesenchymal interactions that are central to development of the secondary palate. However, the gene regulatory networks downstream of Hedgehog (Hh) signaling are incompletely characterized. Here, we show that ectopic Hh signaling in the palatal mesenchyme disrupts oral-nasal patterning of the neural crest cell-derived ectomesenchyme of the palatal shelves, leading to defective palatine bone formation and fully penetrant cleft palate. We show that a series of Fox transcription factors, including the novel direct target Foxl1, function downstream of Hh signaling in the secondary palate. Furthermore, we demonstrate that Wnt/bone morphogenetic protein (BMP) antagonists, in particular Sostdc1, are positively regulated by Hh signaling, concomitant with downregulation of key regulators of osteogenesis and BMP signaling effectors. Our data demonstrate that ectopic Hh-Smo signaling downregulates Wnt/BMP pathways, at least in part by upregulating Sostdc1, resulting in cleft palate and defective osteogenesis.

Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013.

INTRODUCTION: Recent evidence indicates that the choice of intravenous fluids may affect outcomes in critically ill patients. METHODS: We recorded the administration of resuscitation fluids in patients admitted to Australian and New Zealand adult intensive care units (ICUs) for a 24-h period at 6 time points between 2007 and 2013. Changes in patterns of fluid use over this period were determined using regression analyses. RESULTS: Of the 2825 patients admitted to the 61 ICUs on the 6 study days, 754 (26.7%) patients received fluid resuscitation. Of those receiving fluid resuscitation, the proportion of patients receiving crystalloid significantly increased from 28.9% (41/142) in 2007 to 50.5% (48/95) in 2013 (adjusted odds ratio (OR) 2.93; 95% confidence intervals (CI) 1.35-6.33; p = 0.006); of these, the proportion of patients receiving buffered salt solutions significantly increased from 4.9% (7/142) in 2007 to 31.6% (30/95) in 2013 (OR 7.00; 95% CI 2.14-22.92; p = 0.001). The use of colloids significantly decreased from 59.9% (85/142) in 2007 to 42.1% (40/95) in 2013 (adjusted OR 0.34; 95% CI 0.16-0.74; p = 0.007) due to a significant decrease in the proportion of patients receiving gelatin; 28.9% (41/142) to 2.1% (2/95) (OR 0.10; 95% CI 0.03-0.29; p ≤ 0.001). CONCLUSION: Fluid resuscitation practice in Australia and New Zealand adult ICUs has changed over the 6-year study period. Crystalloid use increased primarily due to an increase in the use of buffered salt solutions while overall the use of colloid has decreased.

A review of current statistical methodologies for in-storage sampling and surveillance in the grains industry.

Effective, statistically robust sampling and surveillance strategies form an integral component of large agricultural industries such as the grains industry. Intensive in-storage sampling is essential for pest detection, integrated pest management (IPM), to determine grain quality and to satisfy importing nation's biosecurity concerns, while surveillance over broad geographic regions ensures that biosecurity risks can be excluded, monitored, eradicated or contained within an area. In the grains industry, a number of qualitative and quantitative methodologies for surveillance and in-storage sampling have been considered. Primarily, research has focussed on developing statistical methodologies for in-storage sampling strategies concentrating on detection of pest insects within a grain bulk; however, the need for effective and statistically defensible surveillance strategies has also been recognised. Interestingly, although surveillance and in-storage sampling have typically been considered independently, many techniques and concepts are common between the two fields of research. This review aims to consider the development of statistically based in-storage sampling and surveillance strategies and to identify methods that may be useful for both surveillance and in-storage sampling. We discuss the utility of new quantitative and qualitative approaches, such as Bayesian statistics, fault trees and more traditional probabilistic methods and show how these methods may be used in both surveillance and in-storage sampling systems.

Predicting survival in malignant mesothelioma.

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs. Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis. Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2-1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1-1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0-198), 177 (48-350), 221 (97-504), 238 (108-502) and 301 (134-611) days; ~4 weeks of this apparent improvement can be attributed to earlier diagnosis. With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.

The utility of procalcitonin in diagnosis of H1N1 influenza in intensive care patients.

Procalcitonin (PCT) has been reported to differentiate between bacterial and viral causes of respiratory tract infections. We aimed to assess its ability to discriminate between viral and bacterial infection during the H1N1 pandemic of 2009. The design of this study was a retrospective single centre case series review. Subjects were 17 adult patients admitted to the intensive care unit with suspected or confirmed isolated H1N1 influenza infection, from whom a PCT level was assessed within 24 hours of admission. All patients were admitted during the H1N1 pandemic in Queensland from 6 July 2009 to 2 August 2009. The relationship between PCT levels and H1N1 status was measured by a Wilcoxon rank sum test. Patients were proven to have isolated H1N1 infection as judged by Polymerase Chain Reaction, with no bacterial super-infection. Of this number, 37% had a PCT <1 microg/l, and 63% of patients had an indeterminate PCT between 1 and 10 microg/l. The demographics of all 17 patients were mean age 48.2 years (SD 13.6 years); 59% female; mean Acute Physiological and Chronic Health Evaluation II score 20.3 (SD 5.8); mean intensive care unit 477.5 hours (SD 330.0 hours); 82% of cases required mechanical ventilation; 24% of cases required extracorporeal membrane oxygenation and 94% of cases were alive at intensive care unit discharge. PCT was neither sensitive nor specific in determining isolated H1N1 infection in this series of patients. The use of PCT to assist in isolation triage of patients suspected of infection with H1N1 influenza in the intensive care unit should be made with caution. A larger study may be required.

Pharmacological versus non-pharmacological antipyretic treatments in febrile critically ill adult patients: a systematic review and meta-analysis.

OBJECTIVES: Fever is common in critically ill patients and there are myriad of antipyretic and cooling treatments used. A systematic review was undertaken of the safety and efficacy of methods used to reduce fever. METHODS: Medline, EMBASE, CINAHL and Cochrane Database of Systematic Reviews were searched for randomised control trials (RCTs) of head-to-head and versus placebo/no treatment comparisons of pharmacological and/or non-pharmacological treatments for reducing fever in critically ill adult patients. Primary outcomes were reduction of fever and haemodynamic effects of treatments. RESULTS: 11 of 48 trials reviewed were included. The studies analysed were separated into common antipyretic treatment groups for comparison. Our main findings include, newer versus conventional external cooling therapies where newer external cooling methods (intravascular cooling and hydrogel cooling system) were better at reducing the fever burden than conventional methods (surface cooling) (MD, -8.00, 95% CI=-12.54, -3.47, P<0.001), with a trend for higher mortality for newer methods (RR, 1.42; 95% CI, 0.99-2.03; P=0.06). In the group comparison of the effectiveness of pharmacological antipyretic treatments, reduction on core body temperature favoured continuous antipyretic infusions rather than bolus doses (MD, 0.30, 95% CI 0.09, 0.51, P=0.005). For aggressive versus permissive antipyretic treatments, a reduction in mean daily temperatures favoured the aggressive group (MD, -1.09, 95% CI -1.37, -0.81, P<0.001) with a trend towards higher mortality for aggressive treatment (RR, 6.05, 95% CI 0.78, 46.95, P=0.09). CONCLUSION: Additional studies are needed to explore and clarify the role of antipyretic treatments in febrile critically ill adult patients.

The effect of dexmedetomidine on agitation during weaning of mechanical ventilation in critically ill patients.

Ventilated patients receiving opioids and/or benzodiazepines are at high risk of developing agitation, particularly upon weaning towards extubation. This is often associated with an increased intubation time and length of stay in the intensive care unit and may cause long-term morbidity. Anxiety, fear and agitation are amongst the most common non-pulmonary causes of failure to liberate from mechanical ventilation. This prospective, open-label observational study examined 28 ventilated adult patients in the intensive care unit (30 episodes) requiring opioids and/or sedatives for >24 hours, who developed agitation and/or delirium upon weaning from sedation and failed to achieve successful extubation with conventional management. Patients were ventilated for a median (interquartile range) of 115 [87 to 263] hours prior to enrolment. Dexmedetomidine infusion was commenced at 0.4 microg/kg/hour for two hours, after which concurrent sedative therapy was preferentially weaned and titrated to obtain target Motor Activity Assessment Score score of 2 to 4. The median (range) maximum dose and infusion time of dexmedetomidine was 0.7 microg/kg/hour (0.4 to 1.0) and 62 hours (24 to 252) respectively. The number of episodes at target Motor Activity Assessment Score score at zero, six and 12 hours after commencement of dexmedetomidine were 7/30 (23.3%), 28/30 (93.3%) and 26/30 (86.7%), respectively (P < 0.001 for 6 and 12 vs. 0 hours). Excluding unrelated clinical deterioration, 22 episodes (73.3%) achieved successful weaning from ventilation with a median (interquartile range) ventilation time of 70 (28 to 96) hours after dexmedetomidine infusion. Dexmedetomidine achieved rapid resolution of agitation and facilitated ventilatory weaning after failure of conventional therapy. Its role as first-line therapy in ventilated, agitated patients warrants further investigation.

3,3',5,5'-Tetra-nitro-biphen-yl.

The title compound, C(12)H(6)N(4)O(8), is a biphenyl system that was synthesized as a building block for a new series of anti-malarial compounds. The aromatic rings are oriented at a dihedral angle of 45.5 (2)°, and inter-molecular short O⋯O contacts form a chain along the b axis. The strength of the inter-actions involved in this chain cause one of the rings to be slightly distorted, with the torsion angle between the nitro groups being 23.4 (2)°, whereas, in the other ring, both nitro systems are parallel, forming an angle of 9.6 (2)° with the plane of the aromatic ring to which they are bound. Furthermore, the three ring C atoms around the ring-ring linkage belong to a plane inclined by 4.5 (1)° in relation to the plane containing the other three C atoms, i.e. (NO(2)-)C-C-C(NO(2)). This distortion of the ring causes uncommonly short intermolecular O⋯O [3.038 (2) Å] and O⋯C [3.000 (4) and 3.214 (1) Å] contacts.

Effect of a triaxial nuclear shape on proton tunneling: the decay and structure of 145Tm.

Gamma rays deexciting states in the proton emitter 145Tm were observed using the recoil-decay tagging method. The 145Tm ground-state rotational band was found to exhibit the properties expected for an h{11/2} proton decoupled band. In addition, coincidences between protons feeding the 2{+} state in 144Er and the 2{+}-->0{+} gamma-ray transition were detected, the first measurement of this kind, leading to a more precise value for the 2{+} excitation energy of 329(1) keV. Calculations with the particle-rotor model and the core quasiparticle coupling model indicate that the properties of the pi{11/2} band and the proton-decay rates in 145Tm are consistent with the presence of triaxiality with an asymmetry parameter gamma approximately 20 degrees .

Conversion electron cascades in 254(102)No.

The spectrum of prompt conversion electrons emitted by excited 254No nuclei has been measured, revealing discrete lines arising from transitions within the ground state band. A striking feature is a broad distribution that peaks near 100 keV and comprises high multiplicity electron cascades, probably originating from M1 transitions within rotational bands built on high K states.

Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: the importance of survival as a clinical trial end point.

PURPOSE: The combination of paclitaxel and carboplatin for the treatment of advanced transitional-cell carcinoma (TCC) of the urothelium has promising activity and acceptable toxicity. The purpose of this trial was to evaluate the efficacy of this regimen in a cooperative group setting. PATIENTS AND METHODS: Twenty-nine patients with advanced TCC were treated every 21 days with paclitaxel 200 mg/m(2), administered as a 3-hour infusion, followed by carboplatin dosed to an area under the curve of 5. Prior systemic adjuvant or neoadjuvant platinum-based therapy was not permitted unless completed at least 1 year before enrollment. Patients were evaluated for response every three cycles, and follow-up was conducted to determine survival. RESULTS: Twenty-nine patients were enrolled and were assessable. Four (14%) had received prior adjuvant or neoadjuvant therapy. Node-only disease was present in 24%, and 76% of patients had extranodal disease. The median number of cycles received was five. Grade 4 toxicity consisted primarily of neutropenia (38% of patients). Neurologic toxicity was noted in 16 patients (grade 1 in four patients, grade 2 in five patients, grade 3 in six patients, and grade 4 in one patient). Six partial responses and no complete responses were noted, for a response proportion of 20.7% (95% confidence interval, 8% to 40%). Median progression-free survival time was 4 months, and overall survival time was 9 months. CONCLUSION: The combination of paclitaxel and carboplatin for the treatment of advanced TCC is reasonably well tolerated. However, a response proportion considerably lower than that previously reported was noted. In addition, the median survival time of 9 months was less than the survival time previously reported for patients treated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin. Although our results may reflect enrollment of patients with poor prognostic features, they also call into question the utility of this regimen.

Observations and predictions of secondary neutrons on Space Shuttle and aircraft.

The Cosmic Radiation Effects and Activation Monitor has flown on six Shuttle flights between September 1991 and February 1995 covering the full range of inclinations as well as altitudes between 220 and 570 km, while a version has flown at supersonic altitudes on Concorde between 1988 and 1992 and at subsonic altitudes on a SAS Boeing 767 between May and August 1993. The Shuttle flights have included passive packages in addition to the active cosmic ray monitor which comprises an array of pin diodes. These are positioned at a number of locations to investigate the influence of shielding and local materials. Use of both metal activation foils and scintillator crystals enables neutron fluences to be inferred from the induced radioactivity which is observed on return to Earth. Supporting radiation transport calculations are performed to predict secondary neutron spectra and the energy deposition due to nuclear reactions in silicon pin diodes and the induced radioactivity in the various scintillator crystals. The wide variety of orbital and atmospheric locations enables investigation of the influence of shielding on cosmic ray, trapped proton and solar flare proton spectra.

Health and safety (consultation with employees) regulations 1996.

The Health and Safety Commission (HSC) introduced the Health and Safety (Consultation with Employees) Regulations 1996 (HSCER) on 1st October, 1996. The HSCER 'top up' the existing Safety Representatives and Safety Committees Regulations 1997 (SRSCR). The HSCER require employers to consult with all employees, not just those covered by representatives appointed by recognised trade unions, on matters relating to health and safety. Employers have the choice of consulting whether directly with employees or via elected representatives.

The role of epineurotomy in the operative treatment of carpal tunnel syndrome.

We conducted a prospective, randomized study to evaluate the effect of epineurotomy on the outcome of operative treatment of established median-nerve compression in the carpal canal. Fifty hands (forty-four patients) were randomized into two groups: one group had a release of the transverse carpal ligament alone, and the other had a release and adjuvant epineurotomy of the median nerve. The groups were similar with regard to age, gender, duration of symptoms, and preoperative physical findings. All patients had electrophysiological evidence of sensory delays and fibrillations on preoperative testing. All of the operative procedures were performed by the same surgeon. The patients were evaluated preoperatively and at one year postoperatively. The follow-up examination revealed no detectable differences between the two groups with regard to symptoms, objective findings, or electrophysiological findings. This suggests that epineurotomy of the median nerve offers no benefit compared with sectioning of the transverse carpal ligament alone.

Phase 1 trial of intraperitoneal AD-32 in gynecologic malignancies.

AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.