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.

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.

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.

Obsidian trade routes in the mayan area.

Obsidian from two sources in highland Guatemala has been found at 23 sites of the Classic Mayan civilization, mainly in the nonvolcanic lowlands to the north. The distribution, together with trade routes suggested by topography and documentary sources, suggests efficient waterborne transport and competition between sources for the lowland market.

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.

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.

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.

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.

Lateralized deficits and drug influences on the dichotic listening of schizophrenic patients.

Recall of dichotically presented digit strings was compared between normal controls and 18 chronic schizophrenic patients tested over 12 weeks on chlorpromazine, placebo, and chlorpromazine reinstatement. Patients were subgrouped according to (i) arousal as indexed by orienting responses in a tone-habituation sequence and (ii) paranoid diagnosis. Digits were of equal intensity or differed by 20 dB between the ears and were reported in any order or one ear before the other. Overall, patients performed as well as controls and withdrawal or reinstatement of drug did not reduce accuracy. Patient-control differences occurred when the louder digits were to be reported second and left-hemisphere inhibitory mechanisms were involved, especially when patients were on chlorpromazine. Some lateralized differences in serial position effects found only in patients were interpreted as reflecting left-hemisphere processing impairments. The more aroused patients showed poorer accuracy than the less aroused group due to reduced recall in the left ear. Paranoid patients had superior recall and showed less shifting of attention away from the right ear than nonparanoids. The results are discussed in the context of neurophysiological theories of brain disturbance in schizophrenia.

Phase I trial of carboplatin-cyclophosphamide and iproplatin-cyclophosphamide in advanced ovarian cancer: a Southwest Oncology Group study.

The Southwest Oncology Group has carried out a phase I clinical trial of carboplatin plus cyclophosphamide and iproplatin plus cyclophosphamide in 20 patients with stages III and IV ovarian cancer prior to initiating a phase III trial to compare these platinum analog-cyclophosphamide combinations with standard cisplatin-cyclophosphamide therapy. Myelosuppression proved the dose-limiting toxicity of both the carboplatin (300 mg/m2) plus cyclophosphamide (600 mg/m2) and iproplatin (180 mg/m2) plus cyclophosphamide (600 mg/m2) regimens. Evaluating up to six courses of therapy (repeated at 4-week intervals), the median nadir WBC and platelet counts associated with carboplatin-cyclophosphamide therapy were 1800 (range, 900-4000) and 69 000 per microliter, respectively, and those associated with iproplatin-cyclophosphamide therapy were 1400 (1100-1600) and 140 000 per microliter, respectively. Although the starting doses of carboplatin and iproplatin required a median decrease of 25%, the median doses of each administered through six courses of therapy were 300 and 180 mg/m2, respectively. Neither nephrotoxicity nor neuropathy were experienced by the patients, but mild to moderate nausea and vomiting occurred in more than 75% of those treated with either drug combination. Alopecia of mild to severe degree was observed in 40% of patients. Although the results of this phase I trial are still preliminary, we can recommend for future phase III trials 300 mg/m2 carboplatin and 180 mg/m2 iproplatin when combined with 600 mg/m2 cyclophosphamide repeated a 4-week intervals for six treatment courses.

External imaging techniques for quantitation of distribution of I-131 F(ab')2 fragments of monoclonal antibody in humans.

We have employed noninvasive, external counting techniques for quantitation of I-131 F(ab')2 fragment of mouse monoclonal antibody localized in metastatic lesions and surrounding liver tissue in humans. This method utilizes counts from diametrically opposed views of tumor deposits and surrounding normal tissue. Corrections were made for patient attenuation, lesion size, and surrounding tissue activity. The validity of this method was evaluated using a fillable, tissue-equivalent organ-scanning phantom with organs and tumors of selected size. Less than 10% error was found in quantitation of various activities of I-131 in a 4-cm-diam lesion. Tumor activity ranged from 0.001% to 0.018% of administered dose per cm3 of tissue compared with 0.000 12% to 0.0023% per cm3 of liver. In addition, the vascular clearance of total I-131 and protein-bound I-131 was found to follow a two-compartment model with mean half lives of 3.8 and 21.4 h for total I-131 and 3.9 and 24.4 h for protein-bound I-131.

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.

Pelvic displacement osteotomy for chronic hip dislocation in myelodysplasia.

Twelve children with lumbar-level myelodysplasia (average age, eight and three-quarter years) underwent twenty-one pelvic displacement osteotomies for subluxated or dislocated hips. Nineteen of the twenty-one hips remained reduced on three-year follow-up. Gains in gait pattern, ease of bracing, and reduced pelvic obliquity were noted. Active function about the hips was not improved, nor was there a decrease in the amount of bracing needed following the osteotomy. Pelvic displacement osteotomy can be utilized in selected cases as part of the over-all management of chronic hip dislocation in myelodysplasia.

Gains, losses and lateral differences in the hearing of schizophrenic patients.

Schizophrenic patients, whether newly admitted to hospital or institutionalized, exhibited ear differences in absolute threshold. Right ear thresholds were superior to left ear thresholds especially at frequencies above 2 kHz, but deteriorated in the course of the day or as a result of repeated testing. These effects were attributed to the dynamics of left hemisphere processes which in schizophrenia appear susceptible to inhibition and fatigue, effects that may be endocrine related. Relative to control subjects institutionalized schizophrenic patients showed superior hearing below 1 kHz and inferior hearing above 2 kHz.

Secondary radiation environments in heavy space vehicles and instruments.

Secondary radiations produced by the interactions of primary cosmic rays and trapped protons with spacecraft materials and detectors provides an important, and sometimes dominant, radiation environment for sensitive scientific instruments and biological systems. In this paper the success of a number of calculations in predicting a variety of effects will be examined. The calculation techniques include Monte Carlo transport codes and semi-empirical fragmentation calculations. Observations are based on flights of the Cosmic Radiation Environment and Activation Monitor at a number of inclinations and altitudes on Space Shuttle. The Shuttle experiments included an active cosmic-ray detector as well as metal activation foils and passive detector crystals of sodium iodide which were counted for induced radioactivity soon after return to earth. Results show that cosmic-ray secondaries increase the fluxes of particles of linear energy transfer less than 200 MeV/(gm cm-2), while the activation of the crystals is enhanced by about a factor of three due to secondary neutrons. Detailed spectra of induced radioactivity resulting from spallation products have been obtained. More than a hundred significant radioactive nuclides are included in the calculation and overall close agreement with the observations is obtained.

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.

Sequential complement changes after childhood acute nephritis.

A group of 29 children with acute nephritis have been studied in relation to complement changes during and after their illness. Eighty-two percent had evidence of a streptococcal aetiology. C3 levels were initially depressed in 96.5 percent, but by 12 months all children were normal clinically and had normal complement status. The role of complement is discussed in relation to acute nephritis.