Antagonism between co-infecting gastrointestinal nematodes: A meta-analysis of experimental infections in Sheep.

Gastrointestinal nematodes (GIN) have enormous global impacts in humans, wildlife and grazing livestock. Within grazing livestock, sheep are of particular global importance and the economics and sustainability of sheep production are greatly constrained by GIN infections. Natural infections are composed of co-infections with multiple species, and while some past work suggests species can interact negatively with one another within the same host, there is wide variation in reported patterns. Here, we undertook a systematic literature search and meta-analysis of experimental GIN co-infections of sheep to determine whether these experimental studies support the hypothesis of antagonistic interactions between different co-infecting GIN, and test whether aspects of parasite biology or experimental design influence the observed effects. A systematic search of the literature yielded 4848 studies, within which, we identified 19 experimental sheep studies comparing post-mortem worm counts across two co-infecting GIN species. Meta-analysis of 67 effects obtained from these studies provides strong evidence for interactions between GIN species. There was wide variation in the strength and direction of these interactions, but the global effect was significantly antagonistic. On average, there was a decrease in the number of worms of one species when a co-infecting species was also present, relative to a mono-infection with that species alone. This effect was dependent on the infectious dose and was rapidly lost after anthelmintic treatment, suggesting that live worms are required for the effect to occur. Individual parasite species varied in the extent to which they both exerted, and were subject to, these interspecies interactions, and these differences are more complex than simply co-localisation within the gastrointestinal tract. Antagonistic interactions between co-infecting GIN may feedback into their epidemiology as well as potentially affecting the clinical impacts of infection. Furthermore, the consequences of these interactions may be heightened when clinical interventions affect only one species within the co-infecting network. Whilst it was not possible to identify the causes of variation between GIN species in the impact of co-infection, these findings point to new avenues for epidemiological, clinical and mechanistic research on GIN co-infections.

Modelling bodyweight to avoid anthelmintic underdosing of goats in resources-limited settings.

Improved management of livestock in resource-limited settings can provide a means towards improved human nutrition and livelihoods. However, gastrointestinal nematodes (GIN) are a significant production-limiting factor. Anthelmintics play a role in GIN management; however, few anthelmintic classes are available in many low-middle-income countries. Utilising a limited range of classes may increase selection for anthelmintic resistance; therefore, strategies to reduce other selective pressures are of heightened importance. Avoiding anthelmintic underdosing is one such strategy, but it can be challenging without access to accurate bodyweight measurement. Many previous studies have used thoracic girth as a practical proxy for bodyweight in goats; however, they have rarely considered the potential impact of natural variation on therapeutic doses. Here, the relationship between bodyweight and thoracic girth was modelled using data from 820 goats from three Malawian biomes in two seasons, with the specific aim of avoiding underestimation of bodyweight. The internally cross-validated linear regression (∛Weight ~ 0.053 + 0.040*Girth, R2 = 0.92, rounded up to the nearest 5 kg) was validated against data from an additional 352 Malawian goats (1.4% of goats allocated an underdose and 10.2% allocated a dose > 200% of bodyweight). The equation was further externally validated using an historical dataset of 150 goats from Assam, India (2.7% of goats were allocated to an underdose and 24.8% allocated to a > 200% of bodyweight). These results suggest that a more globally generalisable approach may be feasible, provided the accuracy of the estimate is considered alongside the therapeutic index of the pharmaceutical.

Free-roaming dog population dynamics in Ranchi, India.

Rabies causes approximately 20,000 human deaths in India each year. Nearly all of these occur following dog bites. Large-scale, high-coverage dog rabies vaccination campaigns are the cornerstone of rabies elimination strategies in both human and dog populations, although this is particularly challenging to achieve in India as a large proportion of the dog population are free-roaming and unowned. Further, little is known about free-roaming dog ecology in India which makes defining optimum vaccination strategies difficult. In this study, data collected using a mobile phone application during three annual mass vaccination and neutering (surgical sterilisation of both males and females) campaigns of free-roaming dogs in Ranchi, India (during which a total of 43,847 vaccinations, 26,213 neuter surgeries and 28,172 re-sight observations were made) were interrogated, using two novel approaches to estimate the proportion of neutered dogs that were lost from the city (assumed due to mortality or migration) between campaign years. Analysis revealed high losses of neutered dogs each year, ranging from 25.3% (28.2-22.8) to 55.8% (57.0-54.6). We also estimated that the total population declined by 12.58% (9.89-15.03) over the three-year period. This demonstrates that there is a high turnover of free-roaming dogs and that despite neutering a large number of dogs in an annual sterilisation campaign, the decline in population size was modest over a three-year time period. These findings have significant implications for the planning of rabies vaccination campaigns and population management programmes as well as highlighting the need for further research into the demographics of free-roaming, unowned dogs in India.

A 4 year observation of gastrointestinal nematode egg counts, nemabiomes and the benzimidazole resistance genotypes of Teladorsagia circumcincta on a Scottish sheep farm.

Anthelmintic resistance threatens the sustainability of sheep production globally. Advice regarding strategies to reduce the development of anthelmintic resistance incorporates the outcomes of modelling exercises. Further understanding of gastrointestinal nematode species diversity, and population dynamics and genetics (which may vary between species) is required to refine these models; and field studies combining faecal egg outputs, species composition and resistance genetics are needed to calibrate them. In this study, faecal samples were taken from ewes and lambs on a commercial farm in south-eastern Scotland at approximately 3 t-4 week intervals between spring and autumn over a period of 4 years. Faecal egg counts were performed on these samples, and L3 were collected from pooled coprocultures. Deep amplicon sequencing was used to determine both the species composition of these L3 and the proportions of benzimidazole-resistant single nucleotide polymorphisms in the isotype-1 ß-tubulin locus of the predominant species, Teladorsagia circumcincta L3. Despite consistent management throughout the study, the results show variation in gastrointestinal nematode species composition with time and between age groups, that was potentially associated with weather conditions. The F200Y benzimidazole resistance mutation is close to genetic fixation in the T. circumcincta population on this farm. There was no evidence of variation in isotype-1 ß-tubulin single nucleotide polymorphisms frequency between age groups, and no genetic evidence of reversion to benzimidazole susceptibility, despite targeted benzimidazole usage. This study highlights the need to include speciation when investigating gastrointestinal nematode epidemiology and anthelmintic resistance, and serves as an example of how genetic data may be analysed alongside species diversity and faecal egg counts, when markers for other anthelmintic classes are identified.

Maternity Healthcare Chaplains and Perinatal Post-Mortem Support and Understanding in the United Kingdom and Ireland: An Exploratory Study.

Perinatal autopsy rates have declined significantly in recent decades. There is a lack of consensus concerning the potential religious influences for bereaved parents in their decision making process for post-mortem. This online study of British and Irish maternity healthcare chaplains explored their understanding of general and local perinatal post-mortem procedures and their experiences in the support of parents. Participants included Christian, Muslim and non-faith chaplains. No chaplain identified any religious prohibition to perinatal post-mortem. A majority of chaplains reported that they had been asked about post-mortem by parents; only a minority felt adequately prepared. A key recommendation is that following appropriate training chaplains may be well placed to support colleagues and parents during the decision making process.

Pollination and resource limitation as interacting constraints on almond fruit set.

Pollination and resource availability are factors determining reproductive success of plants, and in agriculture these factors influence yield of fruit-bearing crops. Our understanding of the importance of crop pollination is fast improving, but less is known about how the interaction between pollination and resources constrains fruit production. We conducted an experiment with almond trees (Prunus dulcis) to examine how the number of flowers, light availability and competition for resources affected nut (fruit) production on individual spurs (fruit-bearing structures) exposed to open-pollination or hand-pollination. We found a positive relationship between flower number and nut number on spurs with up to four flowers, but no further benefit after four flowers, suggesting a resource threshold expressed by individual spurs. Spurs with few flowers increased the conversion rate of flowers to nuts when supplemented with hand-pollination, but spurs with more flowers were more likely to achieve the threshold number of nuts even under open-pollination. Our experiment included a further treatment involving spraying whole trees with pollen. This treatment reduced nut production by spurs with many flowers and high light availability, suggesting competition is experienced by well-resourced spurs when resources need to be shared among developing nuts across the whole tree. Our study supports the hypothesis that excess flower production in fruit trees increases the potential for fruit production when pollinator and resource availability is variable (bet-hedging). Spurs with more flowers typically produce more nuts (within a limited range), but only if both resources and pollen supply increase with flower number. For almond growers, a focus on maintaining high flower numbers, especially in high light regions of the canopy, is the foundation for high levels of production. Strategies to lift flower number and light are complicated by trade-offs inherent in tree architecture and orchard design. However, fruit set would be lifted above that achieved by current practice by an increase in the pollination rate of flowers.

Implementation of high coverage mass rabies vaccination in rural Uganda using predominantly static point methodology.

Despite successful eradication programmes in many regions, rabies remains responsible for approximately 60,000 human deaths annually, and no country in Africa is rabies-free. Dogs are the principal reservoir of the virus in Africa and the World Health Organisation recommends that at least 70% of the dog population be vaccinated in order to break the transmission cycle. Most attempts at mass rabies vaccinations in Africa have failed to vaccinate high numbers of dogs at a high coverage. Successful studies have often used a door-to-door (DTD) approach, which is logistically challenging and expensive compared to a static point (SP) approach. Mission Rabies has successfully implemented a combined SP and DTD method in cities in India and Malawi. This campaign used a combined methodology in rural Uganda, starting with a SP campaign, followed by a DTD campaign, and then subsequent transect surveys to assess vaccination coverage. This was facilitated by the use of a smartphone application which recorded all vaccinations and survey responses along with their Global Positioning System location. A total of 4172 dogs were vaccinated in 7 days, attaining an estimated 88.4% coverage. This campaign is of particular note as 95.9% of the vaccinations were performed at SPs. The human-to-dog ratio was 4.9 with a mean dogs per house of 1.2. Most dogs were owned (93.7%). This demonstrates that high-number, high-coverage vaccination is achievable in rural Uganda and provides data that may refine future campaign approaches.

Fetal Dysmorphology-Still an Essential Art. Analysis of the Limitations of Microarray in a Fetal Population and a Look Toward the Genome Sequencing Era.

Cytogenomic microarray allows assessment of the genome at higher resolutions than traditional karyotyping. The objective of this study is to evaluate the utility of microarray in a routine fetal autopsy setting before the advent of routine fetal exome/genome sequencing and the issues these technologies may generate. A systematic review of fetal postmortems at 12-24 weeks gestation between January 2011 and December 2014 was undertaken. Cases where there was no consent for audit, research, or genetic testing were excluded as were cases referred to the Procurator Fiscal, stillbirths, and neonatal deaths. Copy number variations were detected in 16 cases. In addition, there was 1 case of uniparental disomy; not all of these were related to the phenotype. There were a number of cases with phenotypic abnormalities and normal array results. Five of these underwent directed mutation analysis-3 were positive. Genetic laboratory investigations such as microarray and Quantitative Fluorescent-Polymerase Chain Reaction may increase the diagnostic yield in the assessment of fetal dysmorphology. However, this study shows that genetic results not only require careful review given the potential uncertain significance but also require phenotypic assessment of the fetus by a competent fetal dysmorphologist to determine the likely causative effect of any detected anomaly. This best practice will also extend to next generation sequencing and interpretation of variants of unknown significance. Fetal medicine teams should ideally include specialists well versed in assessment of fetal anomaly to provide families with the best possible information about the cause of their pregnancy loss and their options for future pregnancies.

Effects of halogens on European air-quality.

Halogens (Cl, Br) have a profound influence on stratospheric ozone (O3). They (Cl, Br and I) have recently also been shown to impact the troposphere, notably by reducing the mixing ratios of O3 and OH. Their potential for impacting regional air-quality is less well understood. We explore the impact of halogens on regional pollutants (focussing on O3) with the European grid of the GEOS-Chem model (0.25° × 0.3125°). It has recently been updated to include a representation of halogen chemistry. We focus on the summer of 2015 during the ICOZA campaign at the Weybourne Atmospheric Observatory on the North Sea coast of the UK. Comparisons between these observations together with those from the UK air-quality network show that the model has some skill in representing the mixing ratios/concentration of pollutants during this period. Although the model has some success in simulating the Weybourne ClNO2 observations, it significantly underestimates ClNO2 observations reported at inland locations. It also underestimates mixing ratios of IO, OIO, I2 and BrO, but this may reflect the coastal nature of these observations. Model simulations, with and without halogens, highlight the processes by which halogens can impact O3. Throughout the domain O3 mixing ratios are reduced by halogens. In northern Europe this is due to a change in the background O3 advected into the region, whereas in southern Europe this is due to local chemistry driven by Mediterranean emissions. The proportion of hourly O3 above 50 nmol mol-1 in Europe is reduced from 46% to 18% by halogens. ClNO2 from N2O5 uptake onto sea-salt leads to increases in O3 mixing ratio, but these are smaller than the decreases caused by the bromine and iodine. 12% of ethane and 16% of acetone within the boundary layer is oxidised by Cl. Aerosol response to halogens is complex with small (∼10%) reductions in PM2.5 in most locations. A lack of observational constraints coupled to large uncertainties in emissions and chemical processing of halogens make these conclusions tentative at best. However, the results here point to the potential for halogen chemistry to influence air quality policy in Europe and other parts of the world.

[(11)C]Ascorbic and [(11)C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography.

Here we report the radiosynthesis of an endogenous redox pair, [(11)C]ascorbic acid ([(11)C]VitC) and [(11)C]dehydroascorbic acid ([(11)C]DHA), the reduced and oxidized forms of vitamin C, and their application to ROS sensing. These results provide the basis for in vivo detection of ROS using positron emission tomography (PET).

Reproductive performance of Thoroughbred mares in the Waikato region of New Zealand: 1. Descriptive analyses.

AIM: To describe the reproductive performance of a population of Thoroughbred mares on stud farms in the Waikato region of New Zealand. METHODS: A prospective cohort study was performed involving five stud farms in the Waikato region of New Zealand during three consecutive breeding seasons (2006-2008). A total of 1,482 individual mares contributed 2007 mare years and 3,402 oestrous cycles over the three breeding seasons. Mares were served by 87 individual stallions. RESULTS: The mean first-cycle pregnancy rate (FCPR) was 53.6%, the end-of-season pregnancy rate (SPR) was 85.3% and the foaling rate was 80.2%. There were significant differences amongst farms for FCPR (range 47.3-68.2%; p<0.01), SPR (range 81.4-92.6%; p<0.001) and foaling rate (range 77.8-90.1%; p<0.001). There were significant differences amongst stallions in their FCPR (range 38-74%; p<0.001) and SPR (range 72-97%; p<0.001).The proportion of pregnancies lost between day 14-16 and day 42 of gestation was 5.5% and the proportion of pregnancies lost between day 42 and term was 3.0%. Mares older than 14 years of age and barren mares had the highest pregnancy loss rates. Of all pregnancies diagnosed at 14-16 days, 12.9% were multiple pregnancies. The length of the breeding season was relatively short with 87.3% of services occurring in the 91-day period between 1 September and 30 November. CONCLUSIONS: The reproductive performance of Thoroughbred mares in the Waikato region of New Zealand was similar to that reported from other major Thoroughbred breeding countries. Although the per-cycle pregnancy rates in this study were lower than those reported in some studies, the foaling rate was similar to previous reports and this was achieved during a relatively short breeding season.

Reproductive performance of Thoroughbred mares in the Waikato region of New Zealand: 2. Multivariable analyses and sources of variation at the mare, stallion and stud farm level.

AIM: The objective of this study was to utilise multivariable statistical methods appropriate for clustered data to identify mare-related explanatory variables that significantly affected the reproductive performance of Thoroughbred mares in the Waikato region of New Zealand. In addition, we aimed to determine the relative contribution of the mare, stallion and stud farm to reproductive performance. METHODS: A prospective cohort study was performed involving five stud farms in the Waikato region of New Zealand during three consecutive breeding seasons (2006-2008). A total of 1,482 individual mares contributed 2007 mare years and 3,402 oestrous cycles over the three breeding seasons. Reproductive performance was measured using three parameters; (a) first-cycle pregnancy rate (FCPR), (b) end-of-season pregnancy rate (SPR), and (c) the start-of-mating to conception interval. RESULTS: When controlled for the effects of serving stallion, stud farm and year of study the only significant mare-related variables included in the final models of FCPR, SPR and conception interval were the age of the mare and her reproductive status (classified as dry or foaling). Advancing mare age significantly reduced reproductive performance regardless of reproductive status and foaling mares had significantly poorer reproductive outcomes compared with dry mares when controlled for age. For each additional increase in year of age, the FCPR was reduced by a factor of 0.94 (95% CI=0.92-0.96) and the SPR was reduced by a factor of 0.91 (95% CI=0.88-0.93). Mares older than 14 years of age took longer to conceive after the start-of-mating compared with younger mares. The daily hazard of conception for mares 14 years and older was 0.64 (95% CI=0.47-0.83) times less than mares younger than 9 years of age. Determining the relative contribution of the mare, stallion and stud farm to the FCPR indicated that 95.9% of the variation was at the mare level, 4.1% was at the stallion level and 0% was at the stud farm level. For the SPR the variance components indicated that 92.5% of the variation was at the mare level, 6.7% was at the stallion level and 0.8% was at the stud farm level. CONCLUSIONS: The reproductive performance of Thoroughbred mares in the Waikato region of New Zealand is influenced by two main mare-related factors; the age of the mare and her reproductive status (dry or foaling). The majority of variation in reproductive performance was associated with mare-level factors and the contribution of the stallion and stud farm was relatively minor.

Lung effects of inhaled corticosteroids in a rhesus monkey model of childhood asthma.

BACKGROUND: The risks for infants and young children receiving inhaled corticosteroid (ICS) therapy are largely unknown. Recent clinical studies indicate that ICS therapy in pre-school children with symptoms of asthma result in decreased symptoms without influencing the clinical disease course, but potentially affect postnatal growth and development. The current study employs a primate experimental model to identify the risks posed by ICS therapy. OBJECTIVE: To (1) establish whether ICS therapy in developing primate lungs reverses pulmonary pathobiology associated with allergic airway disease (AAD) and (2) define the impact of ICS on postnatal lung growth and development in primates. METHODS: Infant rhesus monkeys were exposed, from 1 through 6 months, to filtered air (FA) with house dust mite allergen and ozone using a protocol that produces AAD (AAD monkeys), or to FA alone (Control monkeys). From three through 6 months, the monkeys were treated daily with ICS (budesonide) or saline. RESULTS: Several AAD manifestations (airflow restrictions, lavage eosinophilia, basement membrane zone thickening, epithelial mucin composition) were reduced with ICS treatment, without adverse effects on body growth or adrenal function; however, airway branching abnormalities and intraepithelial innervation were not reduced. In addition, several indicators of postnatal lung growth and differentiation: vital capacity, inspiratory capacity, compliance, non-parenchymal lung volume and alveolarization, were increased in both AAD and Control monkeys that received ICS treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Incomplete prevention of pathobiological changes in the airways and disruption of postnatal growth and differentiation of airways and lung parenchyma in response to ICS pose risks for developing primate lungs. These responses also represent two mechanisms that could compromise ICS therapy's ability to alter clinical disease course in young children.

The development and evaluation of the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP©) for use by healthcare staff.

BACKGROUND: The early identification of malnutrition and nutrition risk through nutrition screening is common practice in adult clinical care but, in children, this has been hampered by the lack of an appropriate nutrition screening tool. The present study aimed to develop and evaluate a simple, child-specific nutrition screening tool for administration by non-nutrition healthcare professionals. METHODS: In a two-phase observational study, significant predictors of nutrition risk were identified using a structured questionnaire. These were then combined to produce a nutrition screening tool. For evaluation purposes, the reliability, sensitivity and specificity of the newly-developed Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP(©)) were estimated by comparing the classification of nutrition risk using the tool with that determined by a full nutritional assessment by a registered dietitian. RESULTS: A total of 122 children were recruited for development phase and a separate cohort of 238 children was recruited for the evaluation phase. Low percentile weight for age, reported weight loss, discrepancy between weight and height percentile and recently changed appetite were all identified as predictors of nutrition risk. These predictors, together with the expected nutrition risk of clinical diagnoses, were combined to produce STAMP(©). Evaluation of STAMP(©) demonstrated fair to moderate reliability in identifying nutrition risk compared to the nutrition risk classification determined by a registered dietitian (κ = 0.541; 95% confidence interval = 0.461-0.621). Sensitivity and specificity were estimated at 70% (51-84%) and 91% (86-94%), respectively. CONCLUSIONS: The present study describes the development and evaluation of a new nutrition screening tool specifically for use in a UK general paediatric inpatient population.

The atmospheric chemistry of trace gases and particulate matter emitted by different land uses in Borneo.

We report measurements of atmospheric composition over a tropical rainforest and over a nearby oil palm plantation in Sabah, Borneo. The primary vegetation in each of the two landscapes emits very different amounts and kinds of volatile organic compounds (VOCs), resulting in distinctive VOC fingerprints in the atmospheric boundary layer for both landscapes. VOCs over the Borneo rainforest are dominated by isoprene and its oxidation products, with a significant additional contribution from monoterpenes. Rather than consuming the main atmospheric oxidant, OH, these high concentrations of VOCs appear to maintain OH, as has been observed previously over Amazonia. The boundary-layer characteristics and mixing ratios of VOCs observed over the Borneo rainforest are different to those measured previously over Amazonia. Compared with the Bornean rainforest, air over the oil palm plantation contains much more isoprene, monoterpenes are relatively less important, and the flower scent, estragole, is prominent. Concentrations of nitrogen oxides are greater above the agro-industrial oil palm landscape than over the rainforest, and this leads to changes in some secondary pollutant mixing ratios (but not, currently, differences in ozone). Secondary organic aerosol over both landscapes shows a significant contribution from isoprene. Primary biological aerosol dominates the super-micrometre aerosol over the rainforest and is likely to be sensitive to land-use change, since the fungal source of the bioaerosol is closely linked to above-ground biodiversity.

Synergistic effects of osteonectin and brain-derived neurotrophic factor on axotomized retinal ganglion cells neurite outgrowth via the mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 pathways.

Our previous study identified osteonectin (ON) in a screen of factors made by Schwann cells (SCs) which promoted peripheral and central neurons survival and neuritogenesis, however, the mechanisms of ON promoting effects are largely unknown. In the present study, we investigated the effects of ON-deficient SC-conditioned medium (SCCM) and molecular mechanisms of ON, in regulating retinal ganglion cells (RGCs) survival and neurite outgrowth. Neonatal rat RGCs and SCs were purified by immunopanning technique. RGC survival and neuritogenesis reduced significantly when treated with either ON-null mice SCCM or ON-immunodepleted (IP) SCCM (P<0.05). In contrast to wild type SCCM, in the presence of a tyrosine kinase receptor (Trk) inhibitor (K252a), ON-null mice SCCM-induced neuritogenesis were further reduced by 24%. The Trk-mediated signaling pathways became more sensitive to K252a inhibition in the absence of ON. We also showed the synergistic effects of ON and brain-derived neurotrophic factor (BDNF) in promoting RGCs growth and the involvement of ON in two major neurotrophin-mediated signaling pathways, PI-3K-Akt and MAPK-Erk1/2. ON alone activated Akt phosphorylation and increased survival. Blockage of TrkB signalling pathway by TrkB-Fc chimera (BDNF scavenger) or K252a in ON-treated cultures reduced Akt-P level significantly. This suggests that ON induces BDNF synthesis and secretion from RGCs. The enhancement of neuritogenesis and Erk1/2 phosphorylation by ON in BDNF-treated cultures further demonstrate the signaling pathways responsible for the synergistic effect of ON on BDNF-induced neurite outgrowth. To the best of our knowledge, this is the first report showing the synergistic effects of ON on classical neurotrophins which participate in the same signalling pathways in regulating RGC neurite outgrowth.

A hematopoietic stromal lesion associated with fractionated radiotherapy (FxRT): time- and dose-effects.

Earlier, we reported that the local exposure of femoral bone marrow to a clinically-relevant course of fractionated radiotherapy [FxRT; 2.0 Gy (q24h x 5) --> 74 Gy] resulted in the delayed appearance of a stromal lesion which temporally appeared after exposures to a threshold dose of 20 Gy FxRT. To further define this threshold dose, the temporal recovery of blood-forming elements ("cobblestone area" forming colonies; CAFC(7-28d)) and the microenvironmental stroma (long-term bone marrow cultures; LTBMC) of the marrow was examined over a 17-week period following 10 and 30 Gy FxRT. After a subthreshold dose of 10 Gy, each of the 4 CAFC subpopulations were significantly dampened, with recovery initiated within a 6-week interval of 10 Gy of FxRT. Above the threshold dose (30 Gy FxRT), the CAFC subpopulations were again reduced to a level similar to that observed with 10 Gy FxRT. However, after exposures to 30 Gy FxRT, CAFC recovery was significantly well beyond the 6-week interval observed with a 10 Gy Dose of FxRT. Similarly, cell production in LTBMC prepared from marrow exposed to either 10 or 30 Gy FxRT was significantly dampened for at least 3 weeks following the FxRT. Moreover, while cell production in LTBMC derived from marrow exposed to 10 Gy was eventually restored to normal, the dampened cell production observed in LTBMC prepared after 30 Gy FxRT persisted for a period in excess of 17 weeks. Collectively, these observations provide additional support to our earlier observation suggesting that FxRT generates two forms of dose-dependent damage in the marrow: the first an early lesion arising in the blood-forming CAFC subpopulations; the second form, a delayed lesion that involves the persistent expression of a dysfunctional microenvironmental phenotype, appearing to disrupt the normal regulation of hematopoietic stem cell (HSC) proliferation and differentiation of the HSC during the recovery process.

Advice given in community pharmacies to patients with possible oral carcinoma.

We compared advice given by community pharmacy staff in Worcestershire to a proxy consulter on behalf of a patient with a longstanding oral ulcer, presumed to be an oral cancer. If patients seek advice in this way the quality of the advice given is dependent on whether the respondent is a pharmacist or a community pharmacy assistant.