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PIWI-interacting RNAs (piRNA) suppress selfish genetic elements and are essential for germ cell biology in animals. They also play critical roles in regeneration in planaria, regulate gene expression in adult mammalian testes, and participate in antiviral defense in mosquitoes. Inspired by a recent workshop on PIWI proteins and piRNAs, this commentary aims to summarize fundamental aspects of piRNA biology, highlight recent advances, and discuss key outstanding questions. It is written by and for biochemists, geneticists, and evolutionary biologists, and represents our interdisciplinary perspective. This commentary highlights, from an interdisciplinary perspective, recent advances and key outstanding questions in the field of piRNA biology. [ABSTRACT FROM AUTHOR]

Objective: We performed a 1‐year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy‐number‐neutral Absence‐of‐Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non‐causative QF‐PCR result. Methods: After invasive diagnostics, whole exome parent‐offspring trio‐sequencing with exome‐wide CNV analysis was performed in pregnancies with fetal US anomalies and a non‐causative QF‐PCR result (WES‐CNV). On request, additional SNV‐analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV‐analysis afterward) was performed simultaneously (WES‐CNV/SNV) or as rapid SNV‐re‐analysis, following a normal CNV analysis. Results: In total, 415 prenatal samples were included. Following a non‐causative QF‐PCR result, WES‐CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES‐CNV analysis did not reveal a causative aberration, SNV‐re‐analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within 2 weeks after sampling. For SNV‐re‐analysis during pregnancy, turn‐around‐times (TATs) varied between one and 8 days. Conclusion: We show a highly efficient all‐in‐one WES‐based strategy, with short TATs, and the option of rapid SNV‐re‐analysis after a normal CNV result. Key points: What is already known about this topic?Exome sequencing has been implemented in prenatal diagnosis, but is usually offered for single nucleotide variant (SNV) analysis only, after a non‐causative copy number variant (CNV) result obtained with array analysis. What does this study add?This study shows the added value of an all‐in‐one strategy of simultaneously analyzing SNVs, CNVs and copy‐number‐neutral absence‐of‐heterozygosity in whole exome sequencing data for pregnancies with fetal ultrasound anomalies and a non‐causative QF‐PCR result. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study is to evaluate local tumour control rates, radiation side‐effects, visual preservation and disease‐free survival (DFS) of uveal melanoma (UM) patients treated with fractionated stereotactic radiotherapy (fSRT). Methods: A retrospective study of UM patients, who were treated with fSRT (N = 189), was performed by the Rotterdam Ocular Melanoma Study group (ROMS), the Netherlands, between 1999 and 2014 with a follow‐up of at least 5 years. Results: The 1‐, 3‐, 5‐, 10‐ and 15‐year local tumour control rates were as follows: 99.4%, 92.8%, 92.2%, 89.3% and 89.3%, respectively. Cataract (67.8%) was the most common side‐effect of fSRT followed by retinopathy (35.1%), maculopathy (23.8%), vitreous haemorrhage (20.1%), neovascular glaucoma (NVG) (20.0%) and optic neuropathy (12.4%). Patients with anterior located UMs developed cataract more frequently (p = 0.047, multivariable analysis). By multivariable analysis, significant factors for secondary enucleation were tumour recurrence (p < 0.001) and NVG (p < 0.001). In multivariable analysis, risk factors for a worse DFS were larger UM (p = 0.024) and tumours with subretinal fluid (SRF) at baseline (p = 0.038). The 5‐year DFS was 77.0% and the best corrected visual acuity decreased significantly after treatment. After 5 years, 22.0% of patients and after 10 years 17.6% of patients had a visual acuity of ≤0.3 logMAR. Conclusion: Fractionated stereotactic radiotherapy is a good treatment option for small‐, medium‐ and large‐sized tumours with 5‐year local tumour control of 92.2%. After 5 years, 22.0% of the patients had a good vision. Independently of tumour location, the visual acuity decreased significantly after treatment. Overall, the 5‐year DFS was 77.0%. [ABSTRACT FROM AUTHOR]

Background: KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro‐intestinal, cardiovascular, and neurological manifestations. Methods: Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well‐known clinical entities. Results: In an 8‐year‐old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30‐week‐old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction. Conclusion: The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth. [ABSTRACT FROM AUTHOR]

The SETD2‐related overgrowth syndrome is also called “Luscan‐Lumish syndrome” (OMIM 616831) with the clinical characteristics of intellectual disability, speech delay, macrocephaly, facial dysmorphism, and autism spectrum disorders. We report on two novel patients a 4.5‐year‐old boy and a 23‐year‐old female adolescent with a speech and language developmental delay, autism spectrum disorder and macrocephaly, who were both diagnosed with SETD2‐related overgrowth syndrome due to de novo frameshift mutations in the SETD2 gene. Features not previously described which were present in either one of our patients were nasal polyps, a large tongue with creases, a high pain threshold, constipation, and undescended testicles. These features may be related to the syndrome and may need special attention in future patients. Additionally, prevention of obesity should be an important point of attention for patients diagnosed with a SETD2‐related overgrowth syndrome. [ABSTRACT FROM AUTHOR]

Objectives To describe the progress being made in training for minimally invasive surgery ( MIS) in urology. Methods A group of experts in the field provided input to agree on recommendations for MIS training. A literature search was carried out to identify studies on MIS training, both in general and specifically for urological procedures. Results The literature search showed the rapidly developing options for e-learning, box and virtual training, and suggested that box training is a relatively cheap and effective means of improving laparoscopic skills. Development of non-technical skills is an integral part of surgical skills training and should be included in training curricula. The application of modular training in surgical procedures showed more rapid skills acquisition. Training curricula for MIS in urology are being developed in both the USA and Europe. Conclusion Training in MIS has shifted from 'see-one-do-one-teach-one' to a structured learning, from e-learning to skills laboratory and modular training settings. [ABSTRACT FROM AUTHOR]

Elderly men are more likely to be diagnosed with aggressive cancer, but are often inappropriately denied curative treatment. Biological rather than chronological age should be used to decide if a patient will profit from radical treatment. Therefore, every man aged >70 years should undergo a health assessment using a validated tool before making treatment decisions. Fit elderly men with intermediate- or high-risk disease should be offered standard curative local treatment in keeping with guidelines for younger men. Vulnerable and frail elderly men warrant geriatric intervention before treatment. In the case of vulnerable patients, this intervention may render them suitable for standard care. When considering radical prostatectomy outcomes a 'bifecta' of oncological control and continence is appropriate, as erectile dysfunction (although prevalent) has a much smaller impact on quality of life than in younger patients. Radiotherapy is an alternative to radical prostatectomy in men with a life expectancy of <10 years. Primary androgen-deprivation therapy is not associated with improved survival in localised prostate cancer and should only be used for symptom palliation. Further elderly-specific research is needed to guide prostate cancer care. [ABSTRACT FROM AUTHOR]

We aimed to study reproductive behaviour of couples opting for prenatal diagnosis ( PND) and pre-implantation genetic diagnosis ( PGD) for Huntington's disease ( HD). In the Netherlands, exclusion PND is available for persons at 50% risk, whereas exclusion PGD is not allowed. All 162 couples who underwent PND or PGD for HD between 1998 and 2008 and referrals for exclusion PGD to Belgium were included. Couples' reproductive information was collected until December 2010; 132 couples (81.5%) underwent PND in 262 pregnancies, 54 (33.3%) started PGD, and 25 used both. Sixteen percent of PND couples used exclusion PND and 6% used exclusion PGD. The outcomes were 76.5% of PND couples delivered ≥1 unaffected child(ren) after PND, and 44.4% of PGD couples delivered ≥1 PGD child(ren) (mean 2.5 cycles/couple). Couples opting for PGD secondarily (after a previous pregnancy) had more frequently terminated a pregnancy for HD (87.0%) compared with couples secondarily opting for PND (55.2%; p = 0.015). At-risk or HD expansion carrier males were underrepresented in the group of couples primarily opting for PGD (25%) and overrepresented in the secondary PGD group (64%). We conclude that couples reconsider their choices in every subsequent pregnancy based on their previous experience, personal beliefs and the gender of the at-risk partner. [ABSTRACT FROM AUTHOR]

This study aims to give an overview of the number of prenatal tests for Huntington's disease ( HD), test results, and pregnancy outcomes in the Netherlands between 1998 and 2008 and to compare them with available data from the period 1987 to 1997. A total of 126 couples underwent prenatal diagnosis ( PND) on 216 foetuses: 185 (86%) direct tests and 31 (14%) exclusion tests. In 9% of direct tests the risk for the foetus was 25%. Four at-risk parents (4%) carried intermediate alleles. Ninety-one foetuses had CAG expansions ≥36% or 50% risk haplotypes: 75 (82%) were terminated for HD, 12 (13%) were carried to term; four pregnancies were miscarried, terminated for other reasons or lost to follow-up. Unaffected pregnancies (122 foetuses) resulted in the birth of 112 children. The estimated uptake of PND was 22% of CAG expansion carriers (≥36 repeats) at reproductive age. PND was used by two new subgroups: carriers of intermediate alleles and 50% at-risk persons opting for a direct prenatal test of the foetus. A significant number of HD expansion or 50% risk pregnancies were continued. Speculations were made on causative factors contributing to these continuations. Further research on these couples' motives is needed. [ABSTRACT FROM AUTHOR]

van Rij MC, de Die-Smulders CEM, Bijlsma EK, de Wert GMWR, Geraedts JP, Roos RAC, Tibben A. Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntington's disease in the Netherlands. Individuals at 50% risk of Huntington's disease (HD) who prefer not to know their carrier status, might opt for exclusion prenatal diagnosis (ePND) or exclusion preimplantation genetic diagnosis (ePGD). This study aims to provide a better understanding of couples' motives for choosing ePND or ePND, and surveys couples' experiences in order to make recommendations for the improvement of counselling for exclusion testing. This qualitative retrospective interview study focussed on couples who underwent ePND or ePGD for HD in the period 1996-2010. Seventeen couples were included of which 13 had experienced ePND and 6 ePGD. Mean time-interval since exclusion-testing was 3.9 years. Couples' moral reservations regarding termination of pregnancy (TOP) or discarding healthy embryos were counterbalanced by the wish to protect their future child against HD. Seven couples had terminated a total of 11 pregnancies with a 50% HD risk, none showed regret. ePGD was used by couples who wanted to avoid (another) TOP. ePND and ePGD are acceptable reproductive options for a specific group of counsellees. To guarantee sound standards of care, it is imperative that candidate couples be given in-depth non-directive counselling about all possible scenarios, and adequate professional and psychological support prior to, during and after ePND/ePGD. [ABSTRACT FROM AUTHOR]

Limited knowledge is available on Phytophthora infestans populations in Sub-Saharan Africa (SSA). Therefore, and in response to recent severe late blight epidemics, P. infestans isolates from potato, tomato and Petunia × hybrida from eight SSA countries were characterized. Isolates were characterized with 'old' markers, including mating type (176 isolates), mitochondrial DNA haplotype (mtDNA) (281 isolates), glucose-6-phosphate isomerase ( Gpi) (70 isolates), restriction fragment length polymorphism analysis with probe RG-57 (49 isolates), and by metalaxyl sensitivity (64 isolates). Most isolates belonged to the US-1 genotype or its variants (US-1.10 and US-1.11). The exceptions were genotype KE-1 isolates (A1 mating type, mtDNA haplotype Ia, Gpi 90/100 and unique RG-57 genotype), identified in two fields in Kenya, which are related to genotypes previously identified in Rwanda (RW-1 and RW-2), Ecuador and Europe. Metalaxyl-resistant P. infestans isolates from potato were present in all the countries except Malawi, whereas all the isolates from tomato were sensitive. Genotyping of 176 isolates with seven simple sequence repeat (SSR) markers, including locus D13 that was difficult to score, revealed 79 multilocus genotypes (MLGs) in SSA. When this locus was excluded, 35 MLGs were identified. Genetic differentiation estimates between regional populations from SAA were significant when locus D13 was either excluded ( P = 0·05) or included ( P = 0·007), but population differentiation was only low to moderate ( FST = 0·044 and 0·053, respectively). [ABSTRACT FROM AUTHOR]

A description of the course "Developing a Career in Academic Surgery" being offered at the Association for Academic Surgery (AAS) in Australia and New Zealand is provided.

Background: Abdominal aortic aneurysm (AAA) is an important cause of mortality for the aged, a group that has been denied surgery in the past for fear of peri-operative mortality. Is this attitude still justified? Methods: Analysis of prospectively gathered data from a vascular database. Results: 10.9% of all open AAA operations were in patients older than 79 years with an 8% mortality cate compared to 3% for younger patients. For fit elderly patients with ASA scores less than 3, mortality was just under 4%. Renal failure and wound dehiscence were more common in the elderly. Conclusion: When endovascular repair is not possible in a fit elderly patient, open surgery can be performed with acceptable results. [ABSTRACT FROM AUTHOR]

Background: New Zealand, like Australia, has a widely dispersed population in towns at long distances from the main centres. We set out to estimate the in-hospital mortality rate for ruptured abdominal aortic aneurysms in New Zealand and identify factors associated with mortality. Methods: Data were gathered prospectively as part of the Vascular Society of New Zealand’s continuous audit programme of all member surgeons. Data collection was validated by random record audit. In-hospital mortality of ruptured abdominal aortic aneurysms, defined as death during hospital admission irrespective of cause, was determined for the period 1993–2005. Along with other performance indicators, differences in outcomes were assessed to take into account the trend over the time period, hospital size and number of non-operative admissions. Results: Of the 740 patients admitted with a mean age of 73.9 ± 8.5 years, 78% were men and 17.8% were declined an operation. The in-hospital mortality was 48.3% and the operative mortality was 37.8%. With univariate analysis increasing patient age, American Society of Anesthesiology score, hospital size and female sex were predictors of in-hospital mortality. Only age and American Society of Anesthesiology score were independent predictors of operative mortality. Women were less likely to have surgery. Conclusion: Over the past 13 years in-hospital mortality of ruptured abdominal aortic aneurysms in New Zealand remained unchanged. In provincial hospitals the operative outcomes were satisfactory, but the reported number not offered surgery was higher. [ABSTRACT FROM AUTHOR]

Open space preservation is an important aim of spatial planning. In the Netherlands, the recreational, ecological and historic values of open spaces between cities, the buffer zones, are recognised and thus receive ample attention from policy-makers. This paper focuses on Midden-Delfland, an open area in the metropolitan western part of the country. A specific combination of policy instruments and government regulation has made the preservation of open space in this area very successful even compared to other buffer zones. A quantitative analysis of the land-use changes and a more qualitative review of the applied policy instruments are presented here in an attempt to explain this success. The analysis can help planners in finding ways to effectively protect contested open areas. [ABSTRACT FROM AUTHOR]

The ATP-binding cassette A1 (ABCA1) protein regulates plasma high-density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low-HDL individuals and 102 high-HDL individuals. Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C-564T, G-407C, G-278C, and C-14T) identified the C-14T SNP and the TCCT haplotype to be over-represented in low-HDL individuals. The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels. [ABSTRACT FROM AUTHOR]

Gray leaf spot disease (GLS; caused by Cercospora zeae-maydis Tehon and Daniels) is among the major maize (Zea mays L.) production constraints in southern Africa. Maize is predominantly grown by small-scale farmers without fungicides; hence, there is need to develop GLS resistant hybrids. There is limited information about the mode of inheritance for GLS resistance in regionally adapted germplasm. This study was initiated to determine gene action controlling GLS resistance. Seventy-two hybrids were generated by mating 27 inbred lines in a North Carolina design II scheme. Experimental and check hybrids were evaluated in an 8 by 12 α-lattice design with two replications at three locations, during the 2004-2005 season. There was significant variation among the hybrids for GLS resistance and yield. Inbreds L13, L15, L18, L19, and L24, from A, N3, B, K, and SC heterotic groups, respectively, contributed high levels of resistance to hybrids. Both general combining ability (GCA) and specific combining ability (SCA) effects were highly significant (P < 0.01), but the predominance of GCA for GLS (86%) and yield (74%) indicated that additive effects were more important than nonadditive gene action in controlling both traits. Hybrids ranked similarly for GLS across environments, suggesting that few significant crossover genotype by environment interactions, which would cause problems in hybrid selection, were observed. Overall, results indicated that it would be readily possible to develop inbred lines with high GLS resistance from this germplasm. [ABSTRACT FROM AUTHOR]

The ability to predict who will develop perioperative complications remains difficult because the etiology of adverse events is multifactorial. This study examines the preoperative and postoperative ability of the surgeon to predict complications and assesses the significance of a change in prediction. This was a prospective study of 1013 patients. The surgeon assessed the risk of a major complication on a 100-mm visual analog scale (VAS) immediately before and after surgery. When the VAS score was changed, the surgeon was asked to document why. Patients were assessed up to 30 days postoperatively. Surgeons made a meaningful preoperative prediction of major complications (median score = 27mm vs. 19mm, p < 0.01), with an area under the receiver operating characteristic curve of 0.74 for mortality, 0.67 for major complications, and 0.63 for all complications. A change in the VAS score postoperatively was due to technical reasons in 74% of stated cases. An increased VAS score identified significantly more complications, but the improvement in the discrimination was small. When included in a multivariate model for predicting postoperative complications, the surgeon’s VAS score functioned as an independent predictive variable and improved the predictive ability, goodness of fit, and discrimination of the model. Clinical assessment of risk by the surgeon using a VAS score independently improves the prediction of perioperative complications. Including the unique contribution of the surgeon’s clinical assessment should be considered in models designed to predict the risk of surgery. [ABSTRACT FROM AUTHOR]

Background: Wound infection occurs when bacterial contamination overcomes the hosts’ defences against bacterial growth. Wound categories are a measurement of wound contamination. The American Society of Anesthesiologists (ASA) classification of physical status may be an effective indirect measurement of the hosts’ defence against infection. This study examines the association between the ASA score of physical status and wound infection. Methods: A retrospective review of a prospective study of antibiotic prophylaxis was carried out. Patients with a documented ASA score who received optimal prophylactic antibiotics were included. The anaesthetist scored the ASA classification of physical status in theatre. Other risk factors for wound infection were also documented. Patients were assessed up to 30 days postoperatively. Results: Of 1013 patients there were 483 with a documented ASA score. One hundred and one may not have received optimal prophylaxis, leaving a database of 382 patients. There were 36 wound infections (9.4%). Both the ASA classification of physical status ( P = 0.002) and the wound categories ( P = 0.034) significantly predicted wound infection. The duration of surgery, patient’s age, acuteness of surgery and the organ system being operated on did not predict wound infection. On logistic regression analysis the ASA score was the strongest predictor of wound infection. Conclusion: When effective prophylactic antibiotics were used the ASA classification of physical status was the most significant predictor of wound infection. [ABSTRACT FROM AUTHOR]

Background: Limited health resources necessitate prioritization for access to elective cholecystectomy in New Zealand. We aimed to develop and validate a patient questionnaire for determining the effect of gallstone disease on quality of life (QOL) and evaluate its potential role in appraising prioritization and outcomes from surgery. Methods: The Otago gallstones condition-specific questionnaire (CSQ) was designed based on review of published reports, structural equation modelling, input from experts and patient feedback. Fifty-four patients with symptomatic gallstone disease completed the CSQ including a single question asking about global condition impact, along with other QOL measures: the Gallstone Impact Checklist and the Short Form-36 Health Survey. Validity and reliability of the CSQ were assessed using standard psychometric criteria and patient acceptance was explored in a semistructured interview. Patients’ priority status for surgery was determined by two participating surgeons and resulting scores were correlated with the QOL measures. Results: Average CSQ completion time was 2.7 (range 1–5) min and patients found its content concise and comprehensive. Validity was supported through high correlations with the Gallstone Impact Checklist ( r = 0.74), the global condition impact ( r = 0.69) and related dimensions of the Short Form-36 Health Survey. CSQ questions showed satisfactory internal consistency (Cronbach’s α = 0.94) and reproducibility (ICC = 0.93, where ICC is intraclass coefficient). Of all the QOL measures, the CSQ was the most clinically relevant, showing the strongest relationship with surgeon-rated priority ( r = 0.62). Conclusions: Evidence is provided to support the validity of the CSQ for assessing the effect of gallstone disease on QOL. The CSQ could be particularly valuable in aiding priority decisions surgeons make and may be useful in tracking subsequent outcomes. [ABSTRACT FROM AUTHOR]

All trainees are required to keep a logbook as a record of the procedures they have carried out during their surgical training. However, the current logbook is only a record of work carried out and not of the outcome of the operations. It does not prepare the trainee for either a lifetime practice of surgical audit or for a lifetime of learning from the audit process. The logbook requirements of different training boards vary and consequently, trainees find the keeping of a logbook an inconsistent process with ill-defined learning objectives. The Royal Australasian College of Surgeons should define what needs to be collected, how data should be verified and how experience and learning should be reported, and should approve electronic databases that meet logbook standards. The choice of database software and format can then be left to the trainee. Although there are good examples of electronic logbooks being developed, there is, at present, no perfect logbook available. We recommend that all trainees, from the commencement of basic surgical training, should keep a logbook that contains the minimum and expanded datasets in addition to specific trainee data on supervision and learning. In addition to the current reporting format focused on procedural casemix and supervision level, quality/outcome reports and a record of learning are recommended. [ABSTRACT FROM AUTHOR]

Surgical audit is an important part of the process to measure performance, reduce clinical risk and improve quality of care. Recognizing this, the Royal Australasian College of Surgeons established a Surgical Audit Taskforce as a subcommittee of the Board of Continuing Professional Standards. This study aims to review the recommendations of the Taskforce for data collection and peer review. The minimum data for whole-practice, continuing audit have been defined. The method of data collection, devices and databases are personal choices for the individual surgeon. However, there are many benefits of developing an electronic surgical audit, and these include facilitating comparison and sharing of audit data between units. Surgical audits should not only report on work carried out but also ensure that outcomes include key performance indicators such as major complications, readmissions, reoperations, transfers, incident reports, complaints and mortalities. Effective clinical governance demands that issues raised by audit need to be documented and reported together with recommendations for improvement. Surgeons should be proactive in helping to find and implement solutions to the issues arising from surgical audit. [ABSTRACT FROM AUTHOR]

Objective The objectives of the study were to develop a population pharmacokinetic model for 11C-flumazenil at tracer concentrations, to assess the effects of patient-related covariates and to derive an optimal sampling protocol for clinical use. Methods A population pharmacokinetic model was developed using nonlinear mixed effects modelling (NONMEM) with data obtained from 51 patients with either depression or epilepsy. Each patient received ∼370 MBq (1–4 µg) of 11C-flumazenil. The effects of selected covariates (gender, weight, type of disease and age) were investigated. The model was validated using a bootstrap method. Finally, an optimal sampling design was established. Results The population pharmacokinetics of tracer quantities of 11C-flumazenil were best described by a two compartment model. Type of disease and weight were identified as significant covariates ( P < 0.002). Mean population pharmacokinetic parameters (percent coefficient of variation) were: CL 1530 mL min−1 (6.6%), V1 24.8 × 103 mL (3.8%), V2 27.3 × 103 mL (5.4%), and Q 2510 mL min−1 (6.5%). CL was 20% lower in patients with epilepsy, and the influence of weight on V1 was 0.55% kg−1. For the prediction of the AUC, a combination of two time points at t = 30 and 60 min post injection was considered optimal (bias −0.7% (95% CI −2.2 to 0.8%), precision 5.7% (95% CI 4.5–6.9%)). The optimal sampling strategy was cross-validated (observed AUC = 296 MBql−1 min−1 (95% CI 102–490), predicted AUC = 288 MBql−1 min−1 (95% CI 70–506)). Conclusions The population pharmacokinetics of tracer quantities of 11C-flumazenil are well described by a two-compartment model. Inclusion of weight and type of disease as covariates significantly improved the model. Furthermore, an optimal sampling procedure may increase the feasibility and applicability of 11C-flumazenil PET. [ABSTRACT FROM AUTHOR]

The purpose of this study was to lest the hypothesis that cost, as well as frequency of infection, could be used to demonstrate a difference in the performance of prophylactic antibiotics. In a prospective, randomized, double-blind study, 1003 patients undergoing abdominal surgery were given 1 g of intravenous ceftriaxone (R) or cefotaxime (C) at induction of anesthesia, and an additional 500 mg of metronidazole for colorectal surgery. Infection was checked for during the hospital stay and at 30 days postoperatively. The inpatient, outpatient, and community costs of infection were prospectively collected. The frequency of wound infection fur appendectomies when additional metronidazole was not administered was greater with cefotaxime (R 6%, C 18%, p ≤ 0.05), but the cost of infection was the same (average cost R &dollar;994 ± SD &dollar; 1101, C &dollar;878 ± &dollar;1318). For all other procedures, the frequency of wound infection was similar (R 8%, C 10%), but the cost was less with ceftriaxone (R &dollar;887 ± &dollar;1743, C &dollar;2995 ± &dollar;6592, P &lt: 0.05). Ceftriaxone decreased the frequency but not the cost of chest and urinary infection (frequency R 6%, C 11%, p < 0.02, cost R &dollar;1273 ± 2338, C &dollar;1615 ± 4083). Differences in both the frequency and cost of all infection are also presented. Ceftriaxone decreased either the frequency or the cost of different postoperative infections. The cost of infection can increase the discriminatory power of trials comparing antibiotic effectiveness. [ABSTRACT FROM AUTHOR]

Investigates the drug usage and withdrawal in surgical patients in Dunedin, New Zealand. Number of patients taking medicines unrelated to the surgery; Types of unrelated drugs administered; Risks in taking drugs unrelated to surgery.

Examines the incidence of acute colonic pseudo-obstruction cases among the total number of patients with acute colonic obstructions that were admitted at the Dunedin Hospital in New Zealand between 1988 and 1996. Potential etiological factors; Line of treatment used in the hospital; Hospital's experience with colonoscopic decompression.

Presents abstracts related to neurosurgery presented at the Royal Australasian College of Surgeons 1998 Annual Scientific Congress. 'Training in Neurosurgery in the Netherlands and Europe,' by H.A.M. van Alphen; 'Spinal Cord Dynamics,' by R. Jones and J. Pereira.

The ESF-EMBO conference on 'Antiviral RNAi: From Molecular Biology towards Applications' took place in June 2012 in Pultusk, Poland. It brought together scientists working at the interface of RNAi and virus infections in different organisms, covering the complete range from basic mechanisms of RNA silencing to RNAi-based antiviral therapy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses a case of a 10-year-old boy with Chinese descent presented with abdominal pain, wherein hispathology shows a normal appendix but the mass excised is conclusive of histiocystic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease.

The author reflects on the potential shortage of the surgical workforce in Australia in the future. He cites one study emphasizing that the shortage does affect surgeons' surgical practices as they are faced with higher workload than the usual. To address the issue, he considers the plan of forming student surgical interest society which is being pursued in the Wellington School of Medicine at the University of Otago. He also suggests surgeons to share their knowledge with medical students.

A reply to a letter to editor is presented in response to the study over the use of judgment analysis in modeling the estimation of risk by a surgeon.

A letter to the editor is presented that discusses the excision of sciatic notch dumb-bell tumors through lower midline abdominal incision and transgluteal incision.

Purpose The Otago Varicose Veins Condition-Specific Questionnaire (OCSQ) is a validated quality of life (QOL) tool for use in the pre-treatment setting. This follow-on study investigates how the OCSQ reflects changes in QOL following treatment, and how these changes relate to clinical and vascular laboratory outcomes. Methodology Patients with varicose veins undergoing pre-treatment assessment at the Otago Vascular Laboratory were recruited. The OCSQ was administered at the time of assessment and at 1, 3, 6, and 12 months post-treatment. A follow-up laboratory assessment was performed at 12 months. Pre and post-treatment QOL at each time point were compared. The relationships between QOL, patient demographics and laboratory measures were examined. Results Of the 218 patients, the average pre-treatment QOL score was 26.3% ± 17.3 (a higher score indicates a poorer QOL), and following treatment the scores improved at all time points (p < 0.05). The effect sizes were moderate to large, and the greatest QOL was seen at 3 months (11.3% ± 12.5). There was an association between longer prior disease duration and poorer QOL at 3 months (r = 0.31, p < 0.01), and between older age and poorer QOL at 12 months (r = 0.31, p < 0.01). Patients having treatment for recurrent disease showed lower levels of QOL than those with primary disease. Apart from the Venous Clinical Severity Score, no laboratory measure correlated with QOL. Conclusions The OCSQ is a useful tool in evaluating QOL following treatment for varicose veins. Changes in QOL are not well reflected in laboratory measures. Age, prior disease duration, and recurrent disease seem to limit the improvement in QOL following treatment. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Using Cost of Infection as a Tool to Demonstrate a Difference in Prophylactic Antibiotic Efficacy: A Prospective Randomized Comparison of the Pharmacoecomonic Effectiveness of Ceftriaxone and Cefotaxime Prophylaxis in Abdominal Surgery."