Improving antibiotic use in hospitals: development of a digital antibiotic review tracking toolkit (DARTT) using the behaviour change wheel.

OBJECTIVE: To develop a theory-informed behaviour change intervention to promote appropriate hospital antibiotic use, guided by the Medical Research Council's complex interventions framework. METHODS: A phased approach was used, including triangulation of data from meta-ethnography and two qualitative studies. Central to intervention design was the generation of a robust theoretical basis using the Behaviour Change Wheel to identify relevant determinants of behaviour change and intervention components. Intervention content was guided by APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, and Equity) criteria and coded using a Behaviour Change Technique Taxonomy. Stakeholders were involved throughout. RESULTS: From numerous modifiable prescribing behaviours identified, active 'antibiotic time-out' was selected as the target behaviour to help clinicians safely initiate antibiotic reassessment. Prescribers' capability, opportunity, and motivation were potential drivers for changing this behaviour. The design process resulted in the selection of 25 behaviour change techniques subsequently translated into intervention content. Integral to this work was the development and refinement of a Digital Antibiotic Review Tracking Toolkit. CONCLUSION: This novel work demonstrates how the Behaviour Change Wheel can be used with the Medical Research Council framework to develop a theory-based behaviour change intervention targeting barriers to timely hospital antibiotic reassessment. Future research will evaluate the Antibiotic Toolkit's feasibility and effectiveness.

Blood Biomarkers from Research Use to Clinical Practice: What Must Be Done? A Report from the EU/US CTAD Task Force.

Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.

Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy.

There are growing numbers of adults with Duchenne Muscular Dystrophy living well into their fourth decade. These patients have complex medical needs that to date have not been addressed in the International standards of care. We sought to create a consensus based standard of care through a series of multi-disciplinary workshops with specialists from a wide range of clinical areas: Neurology, Cardiology, Respiratory Medicine, Gastroenterology, Endocrinology, Palliative Care Medicine, Rehabilitation, Renal, Anaesthetics and Clinical Psychology. Detailed reports of evidence reviewed and the consensus building process were produced following each workshop and condensed into this final document which was approved by all members of the Adult North Star Network including service users. The aim of this document is to provide a framework to improve clinical services and multi-disciplinary care for adults living with Duchenne Muscular Dystrophy.

Paid- and family-carers' views on supporting women with intellectual disability through breast screening.

The cancer needs of people with intellectual disabilities are increasingly being debated. This paper explores the views and experiences of paid- and family-carers when supporting women with intellectual disabilities through breast screening. An ethnographic approach was drawn on and purposive sampling methods were employed. One-to-one semi-structured interviews with 13 carers (10 paid-carers, three family-carers) were undertaken and supported by periods of focused observation on behaviour related to breast awareness and breast screening. Findings indicated that most women with intellectual disabilities needed some support but the quality and quantity of support depended upon both the woman's level of intellectual disability and who was supporting them. In terms of breast screening, the findings suggested that the women were potentially being let down at all the different stages of the breast screening process, from the arrival of the invitation letter to the experience of having a mammogram. The conclusion drawn was that there was evidence of equality of service provision but inequality of service delivery and uptake.

Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE).

CONTEXT: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes. METHODS: This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height. RESULTS: FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P < .05) and in moderately affected genotype group B women than either more severely affected groups null and A (P < .01) or the mildest group C (P < .001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life. CONCLUSIONS: Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

Evaluation of multiplex polymerase chain reaction utilising multiple targets in Mycobacterium tuberculosis direct test negative but culture positive cases: a potential method for enhancing the diagnosis of tuberculosis.

PURPOSE: To evaluate multiplex Polymerase Chain Reaction (MPCR) utilising multiple targets (IS6110, Protein b [Pab] and MPB64 genes) in Mycobacterium tuberculosis Direct Test (MTD) negative but culture positive cases and comparison of MPCR with Real-Time polymerase chain reaction (RT-PCR) for diagnosis of tuberculosis. MATERIALS AND METHODS: MPCR was carried out on 28 culture positive sputum samples. Out of 28 culture positive samples, 17 were originally reported, as MTD test negative and 11 were MTD test positive, respectively. The results of MPCR were compared with RT-PCR. To check the specificity of the tests, MPCR and RT-PCR were also evaluated with 16 non-tuberculous mycobacterial (NTM) isolates. RESULTS: Out of 28 culture positive sputum samples, MPCR was positive in all 28/28 samples, whereas RT-PCR was positive in 27/28 samples and MTD test was originally tested positive in six sputum samples and on repeating MTD testing, five more sputum samples were positive and thus total number of MTD positive were 11/28 sputum samples, respectively. All the tests were negative on evaluation with all the 16 NTMs, thus giving specificity of 100% to all the tests; sensitivity of MPCR, RT-PCR and MTD tests were 100%, 96.42% and 39.28%, respectively, in these specifically selected samples. CONCLUSIONS: MPCR may be an important tool in the rapid diagnosis of tuberculosis especially in disease endemic, resource limited countries.

First Report of Soybean Vein Necrosis Disease Caused by Soybean vein necrosis-associated virus in Wisconsin and Iowa.

Several viral diseases of soybean (Glycine max) have been identified in the north-central U.S. soybean production area, which includes Wisconsin and Iowa (2). Previously, Soybean vein necrosis disease (SVND) caused by Soybean vein necrosis-associated virus was reported in Arkansas, Tennessee, and other southern states (4). In September 2012, soybean plants with symptoms similar to those reported for SVND (4) were observed in fields across Wisconsin and Iowa. Symptoms included leaf-vein and leaf chlorosis, followed by necrosis of the leaf veins and eventually necrosis of the entire leaf. Six samples with symptoms indicative of SVNaV were collected from research plots located at the West Madison Agricultural Research Station located in Madison, WI. An additional three samples were collected from three locations in central Iowa. Total RNA extracted from each sample using the Trizol Plus RNA purification kit (Invitrogen, Carlsbad, CA) was used to generate complementary DNA (cDNA) using the iScript cDNA synthesis kit (Bio-Rad Laboratories, Hercules, CA) following the manufacturers' suggested protocols. The resulting cDNA was used as template in a PCR with SVNaV-specific primers, SVNaV-f1 and SVNaV-r1 (3). PCRs of two of the six Wisconsin samples and two Iowa samples were positive. Amplification products were not detected in the other five samples. The amplification products from the four strongly positive samples were purified using the Wizard SV Gel and PCR Purification Kit (Promega, Madison, WI) following the manufacturer's suggested protocol and were subjected to automated sequencing (University of Wisconsin Biotechnology Center or Iowa State University, DNA Sequencing Facilities). BLASTn (1) alignments of the 915-bp consensus sequence revealed 98% and >99% identity of the Wisconsin and Iowa samples, respectively, with the 'S' segment of the SVNaV 'TN' isolate (GenBank Accession No. GU722319.1). Samples from the same leaf tissue used above, were subjected to serological tests for SVNaV using antigen coated-indirect ELISA (3). Asymptomatic soybeans grown in the greenhouse were used as a source of leaves for negative controls. These tests confirmed the presence of SVNaV in eight symptomatic soybean leaflets collected in Wisconsin and Iowa. The asymptomatic control and one Iowa sample, which was also PCR-negative, were also negative by serological testing. Six additional samples from soybean fields in as many Wisconsin counties (Fond Du Lac, Grant, Green, Juneau, Richland, Rock) tested positive for SVNaV using specific primers that amplify the 'L' segment (4). The sequenced amplification products (297-bp) showed 99 to 100% homology to the L segment of the TN isolate (GU722317.1). To our knowledge, this is the first report of SVNaV associated with soybean and the first report of SVND in Wisconsin and Iowa. Considering that little is known about SVNaV, it is assumed that it is like other Tospoviruses and can cause significant yield loss (4). Soybean is a major cash crop for Wisconsin and Iowa, and infection by SVNaV could result in potential yield loss in years where epidemics begin early and at a high initial inoculum level. References: (1) S. F. Altschul et al. J. Mol. Biol. 215:403, 1990. (2) G. L. Hartman et al. Compendium of Soybean Diseases, 4th ed, 1999. (3) B. Khatabi et al. Eur. J. Plant Pathol. 133:783, 2012. (4) J. Zhou et al. Virus Genes 43:289, 2011.

Glucocorticoid treatment regimen and health outcomes in adults with congenital adrenal hyperplasia.

BACKGROUND: Adults with congenital adrenal hyperplasia (CAH) are treated with a wide variety of glucocorticoid treatment regimens. OBJECTIVE, DESIGN AND METHODS: To test whether drug dose and timing of glucocorticoid treatment regimen impacts on health outcomes. This was a cross-sectional study of 196 adult CAH patients in whom treatment and health outcomes were measured. Glucocorticoid dose was converted to prednisolone dose equivalent (PreDEq) using three published formulae. Associations between the type of glucocorticoid regimen and PreDEq with specific health outcome variables were tested using partial correlation and principal components analysis (PCA). RESULTS: Patients on dexamethasone had lower androgens and ACTH but greater insulin resistance compared with those receiving hydrocortisone or prednisolone. Dexamethasone dose and once daily administration were associated with insulin resistance. Partial correlation analysis adjusted for age and sex showed PreDEq weakly correlated (r < 0·2) with blood pressure and androstenedione. Mutation severity was associated with increased PreDEq (F(3,141)  = 4·4, P < 0·01). In PCA, 3 PCs were identified that explained 62% of the total variance (r(2) ) in observed variables. Regression analysis (age and sex adjusted) confirmed that PC2, reflecting disease control (androstenedione, 17-hydroxypregesterone and testosterone), and PC3, reflecting blood pressure and mutations (systolic and diastolic blood pressure and mutation severity), related directly to PreDEq (r(2)  = 23%, P < 0·001). CONCLUSIONS: In adults with congenital adrenal hyperplasia, dexamethasone use was associated with lower androgens but greater insulin resistance, and increasing glucocorticoid dose associated with increased blood pressure, poor disease control and mutation severity.

Blebbishields, the emergency program for cancer stem cells: sphere formation and tumorigenesis after apoptosis.

Caspases mediate apoptosis and have also been implicated in stem-cell biology. How caspases are linked to stem-cell biology is not known. Here, we show that the apoptotic blebs of cancer cells fuse together to form novel structures called 'blebbishields'. Blebbishields form spheres by fusion. Both blebbishield formation and sphere formation involve active caspases and N-linked glycosylation. Sphere formation is enhanced by acidic pH and is counteracted by inhibitors of proton pump, caspases, and cholesterol. The blebbishields from VEGFR2(High) cells are capable of enhanced sphere formation. Blebbishields express transiently downregulated stem-cell markers and the sphere-forming blebbishield-derived cells are tumorigenic. Our study demonstrates that the cancer stem cells can survive after apoptosis by blebbishield formation and subsequent sphere formation.

Treatment outcomes of a stage 1 cognitive-behavioral trial to reduce alcohol use among human immunodeficiency virus-infected out-patients in western Kenya.

AIMS: Dual epidemics of human immunodeficiency virus (HIV) and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. The purpose of this study was to test the preliminary efficacy of a culturally adapted six-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected out-patients in Eldoret, Kenya. DESIGN: Randomized clinical trial comparing CBT against a usual care assessment-only control. SETTING: A large HIV out-patient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration. PARTICIPANTS: Seventy-five HIV-infected out-patients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking. MEASUREMENTS: Percentage of drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Time line Follow back method. FINDINGS: There were 299 ineligible and 102 eligible out-patients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large [d=0.95, P=0.0002, mean difference=24.93, 95% confidence interval (CI): 12.43, 37.43 PDD; d=0.76, P=0.002, mean difference=2.88, 95% CI: 1.05, 4.70 DDD]. Randomized participants attended 93% of the six CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69% (CBT) and 38% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the United States. Treatment effect sizes were comparable to alcohol intervention studies conducted in the United States. CONCLUSIONS: Cognitive-behavioral therapy can be adapted successfully to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan out-patients.

Comparison of radiotherapy treatment plans for left-sided breast cancer patients based on three- and four-dimensional computed tomography imaging.

AIMS: The target volume for breast radiotherapy after conservative surgery for breast cancer may be affected by breathing motion. We investigated differences between conventional and four-dimensional computed tomography-based treatment planning and whether gating could improve dose volume parameters. MATERIALS AND METHODS: Ten patients with left-sided breast cancer and surgical clips at the excision site had conventional treatment planning computed tomography and four-dimensional computed tomography. Treatment plans using two tangential beams (6 MV X-rays) were optimised for target coverage and homogeneity using a field in field technique for the three-dimensional scan. This plan was applied directly to four-dimensional datasets representing individual phases of the breathing cycle and combinations thereof (average and maximum intensity projection). Optimised plans were generated for the maximum inhalation scan to study what could potentially be achieved in gated radiotherapy. RESULTS: Four-dimensional computed tomography with effective doses of around 10 mSv proved to be adequate for treatment planning in all patients. The average motion of the surgical clips was 3.7 mm (range 1.7-6.5mm), which was similar to the movement of the chest wall. With a margin of 7 mm for the whole breast to planning target volume, conventional three-dimensional computed tomography-based planning was found to adequately cover the target as seen on four-dimensional computed tomography without significant differences in normal tissue sparing. Improved sparing of the heart and lung could only be achieved by reducing the posterior margin of the target volume, which may be justified if four-dimensional computed tomography is used to determine the target and its motion. CONCLUSION: No significant benefit has been shown for the use of four-dimensional computed tomography-based planning if motion management is not implemented concurrently with a reduced posterior margin between clinical and planning target volumes.

Exploring spatial distributions of larval yellow perch Perca flavescens, bluegill Lepomis macrochirus and their prey in relation to wind.

The objectives of the present study were to determine if spatial differences existed between zooplankton, larval yellow perch Perca flavescens and bluegill Lepomis macrochirus (<13 mm total length, L(T)) in Pelican Lake (332 ha), NE, U.S.A. It was hypothesized that wind could act as a transport mechanism for larval fishes in this shallow lake, because strong winds are common at this geographic location. Potential spatial differences were explored, relating to zooplankton densities, size structure and densities of larval P. flavescens and L. macrochirus. Density differences (east v. west side of the lake) were detected for small- (two occasions), medium- (two occasions) and large-sized (one occasion) L. macrochirus larvae. No density differences were detected for small P. flavescens larvae; however, densities of medium- and large-sized P. flavescens were each higher on the west side of the lake on two occasions. There was no evidence that larval P. flavescens and L. macrochirus distributions were related to wind because they were not associated with large wind events. Likewise, large wind event days did not result in any detectable spatial differences of larval P. flavescens and L. macrochirus densities. There appeared to be no spatial mismatch between larval densities and associated prey in the years examined. Thus, wind was not apparently an influential mechanism for zooplankton and larval P. flavescens and L. macrochirus transport within Pelican Lake, and spatial differences in density may instead be related to vegetation and habitat complexities or spawning locations within this shallow lake.

Detection and variability of aster yellows phytoplasma titer in its insect vector, Macrosteles quadrilineatus (Hemiptera: Cicadellidae).

The aster yellows phytoplasma (AYp) is transmitted by the aster leafhopper, Macrosteles quadrilineatus Forbes, in a persistent and propagative manner. To study AYp replication and examine the variability of AYp titer in individual aster leafhoppers, we developed a quantitative real-time polymerase chain reaction assay to measure AYp concentration in insect DNA extracts. Absolute quantification of AYp DNA was achieved by comparing the amplification of unknown amounts of an AYp target gene sequence, elongation factor TU (tuf), from whole insect DNA extractions, to the amplification of a dilution series containing known quantities of the tuf gene sequence cloned into a plasmid. The capabilities and limitations of this method were assessed by conducting time course experiments that varied the incubation time of AYp in the aster leafhopper from 0 to 9 d after a 48 h acquisition access period on an AYp-infected plant. Average AYp titer was measured in 107 aster leafhoppers and, expressed as Log10 (copies/insect), ranged from 3.53 (+/- 0.07) to 6.26 (+/- 0.11) occurring at one and 7 d after the acquisition access period. AYp titers per insect and relative to an aster leafhopper chromosomal reference gene, cp6 wingless (cp6), increased approximately 100-fold in insects that acquired the AYp. High quantification cycle values obtained for aster leafhoppers not exposed to an AYp-infected plant were interpreted as background and used to define a limit of detection for the quantitative real-time polymerase chain reaction assay. This method will improve our ability to study biological factors governing AYp replication in the aster leafhopper and determine if AYp titer is associated with frequency of transmission.

Maxillofacial trauma and the GDP--specialty recognition and patterns of referral.

OBJECTIVE: To investigate New Zealand GDPs' awareness of maxillofacial trauma and to identify their associated referral patterns. DESIGN: Cross-sectional survey of a random sample of GDPs. METHOD: A nationwide postal questionnaire survey was sent to GDPs on the New Zealand Dental Register, maintained by the Dental Council of New Zealand. The questionnaire requested socio-demographic details, together with information on the availability of specialist services and their need for continuing professional development in oral and maxillofacial surgery (OMS). The questionnaire also asked the GDPs to indicate which specialty (plastic surgery, ear nose and throat (ENT) surgery, OMS and Other) they expected to manage--and to which specialty they would refer-seven types of maxillofacial injury. RESULTS: Some 377 GDPs responded (76.6%). The majority of GDPs expected OMS to manage maxillofacial trauma, except for facial lacerations and isolated nasal fractures which were expected to be managed by plastic surgery (83.0%) and ENT surgery (79.7%), respectively. Most GDPs (48.0% to 87.9%) referred maxillofacial trauma to OMS, except for isolated nasal fractures, for which there were similar proportions referred to ENT surgery and OMS (45.8% and 41.4%, respectively). Differences in awareness of and referral patterns for maxillofacial trauma were identified by dentist characteristics. Most GDPs (96.0%) felt there was a need for continuing professional development in OMS, and most (84.1%) preferred this to be in the form of lectures and seminars. CONCLUSION: The first-ever study of GDP referral patterns for maxillofacial trauma in New Zealand has revealed that most GDPs in New Zealand referred maxillofacial trauma appropriately to OMS.

Audiovisual interventions to reduce the use of general anaesthesia with paediatric patients during radiation therapy.

Clinical audiovisual interventions were implemented to avoid the use of general anaesthesia with children undergoing radiation therapy treatment. A retrospective audit and case study review was conducted to evaluate the utility of distraction interventions aimed at improving immobilisation and reducing separation anxiety for children aged between 2 and 6 years old who received radiation therapy. A simple, inexpensive audiovisual system was established using commercially available equipment. Paediatric patients could elect to (i) use a closed-circuit TV system that allowed them to see their carer(s); (ii) watch a DVD movie; or (iii) listen to carer(s) on a microphone during their treatment. Over a 2-year period (March 2007-May 2009), 37 paediatric patients aged 2-6 years received radiation therapy at the centre. Twenty-four children participated in audiovisual interventions, and 92% (n = 22) of these children did not require the use of general anaesthesia for some or all of their treatment. Case study review illustrates the utility and limitations of the system. The audit and case studies suggest that the audiovisual interventions provided supportive care and reduced the need to anaesthetise children undergoing radiation therapy treatment.

Systematic cultural adaptation of cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in western Kenya.

Two-thirds of those with HIV worldwide live in sub-Saharan Africa. Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence. In western Kenya, hazardous drinking was reported by HIV (53%) and general medicine (68%) outpatients. Cognitive behavioral treatment (CBT) has demonstrated strong efficacy to reduce alcohol use. This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Following adaptation and counselor training, five pilot groups were run (n = 27). Overall attendance was 77%. Percent days abstinent from alcohol (PDA) before session 1 was 52-100% (women) and 21-36% (men), and by session 6 was 96-100% (women) and 89-100% (men). PDA effect sizes (Cohen's d) between first and last CBT session were 2.32 (women) and 2.64 (men). Participants reported treatment satisfaction. Results indicate feasibility, acceptability and preliminary efficacy for CBT in Kenya.

Centre credentialing for Trans Tasman Radiation Oncology Group trial 06.02: multicentre feasibility study of accelerated partial breast irradiation.

INTRODUCTION: Inconsistencies in contouring target volumes for partial breast irradiation (PBI) may result in geographical misses and compromise treatment outcomes. The present study aimed to (1) determine the variability of the target volumes contoured and treatment plans generated by participating centres in credentialing for participation in a multicentre PBI trial; and (2) assess dosimetric changes when standardized target volumes were used. METHODS: The CT image sets of two de-identified patients post-breast conserving surgery were used. Contouring of the target volumes for the two cases was performed and a treatment plan as per protocol specifications was generated for each case by the seven participating centres. Planning of both cases was repeated by five centres using a set of standardized target volumes to evaluate resulting dosimetric changes in the treatment plans. RESULTS: The surgical cavity, the part of the planning target volume used for dose evaluation and ipsilateral whole breast volumes contoured by the centres varied by 25%, 16% and 21% (1 standard deviation), respectively. The dosimetric variations found when the standardized target volumes were used were smaller than those noted when centre-specific volumes were used. The volumes of the ipsilateral lungs receiving 30% of the prescribed dose and the volumes of the ipsilateral whole breasts receiving 95% and 50% of the prescribed dose were reduced in the treatment plans developed using the standardized target volumes. CONCLUSIONS: Given the impact of contouring on dose distributions, quality assurance procedures in clinical trials of PBI need to take into account both the technical approaches and the contouring.

A spreadsheet to determine the volume ratio for target and breast in partial breast irradiation.

The technical feasibility of Partial Breast Irradiation (PBI) using external beam radiotherapy depends on the ratio between the evaluation planning target volume (PTV_eval) and the whole breast volume ("PBI volume ratio" = PVR). We aimed to develop a simple method to determine PVR using measurements performed at the time of the planning CT scan. A PVR calculation tool was developed using a Microsoft Excel spreadsheet to determine the PTV from three orthogonal dimensions of the seroma cavity and a given margin on the CT scans. The breast volume is estimated from the separation and breast height in five equally spaced CT slices. The PTV_eval and whole breast volume were determined for 29 patients from two centres using the spreadsheet calculation tool and compared to volumes delineated on computerised treatment planning systems. Both the PTV_eval and whole breast volumes were underestimated by approximately 25% using the spreadsheet. The resulting PVRs were 1.05 +/- 0.35 (mean +/- 1SD) times larger than the ones determined from planning. Estimations of the PVR using the calculation tool were achievable in around 5 minutes at the time of CT scanning and allow a prompt decision on the suitability of the patients for PBI.

A soluble form of the Tomato spotted wilt virus (TSWV) glycoprotein G(N) (G(N)-S) inhibits transmission of TSWV by Frankliniella occidentalis.

Tomato spotted wilt virus (TSWV) is an economically important virus that is transmitted in a persistent propagative manner by its thrips vector, Frankliniella occidentalis. Previously, we found that a soluble form of the envelope glycoprotein G(N) (G(N)-S) specifically bound thrips midguts and reduced the amount of detectable virus inside midgut tissues. The aim of this research was to (i) determine if G(N)-S alters TSWV transmission by thrips and, if so, (ii) determine the duration of this effect. In one study, insects were given an acquisition access period (AAP) with G(N)-S mixed with purified virus and individual insects were assayed for transmission. We found that G(N)-S reduced the percent of transmitting adults by eightfold. In a second study, thrips were given an AAP on G(N)-S protein and then placed on TSWV-infected plant material. Individual insects were assayed for transmission over three time intervals of 2 to 3, 4 to 5, and 6 to 7 days post-adult eclosion. We observed a significant reduction in virus transmission that persisted to the same degree throughout the time course. Real-time reverse transcription polymerase chain reaction analysis of virus titer in individual insects revealed that the proportion of thrips infected with virus was reduced threefold when insects were preexposed to the G(N)-S protein as compared to no exposure to protein, and nontransmitters were not infected with virus. These results demonstrate that thrips transmission of a tospovirus can be reduced by exogenous viral glycoprotein.