Task-based measures of sensitivity to physical activity predict daily life pain and mood among people living with back pain.

BACKGROUND: Clinical interventions aim to improve the daily life experiences of patients. However, past research has highlighted important discrepancies between commonly used assessments (e.g. retrospective questionnaires) and patients' daily life experiences of pain. These gaps may contribute to flawed clinical decision-making and ineffective care. Recent work suggests that real-time, task-based clinical assessments may help reduce these discrepancies by adding predictive value in explaining daily life pain experiences. This study aimed to investigate these relationships by evaluating whether task-based measures of sensitivity to physical activity (SPA) predict daily life pain and mood, beyond traditional pain-related questionnaires. METHODS: Adults with back pain (<6-month onset) answered pain-related questionnaires and completed a standardized lifting task. SPA-Pain, SPA-Sensory and SPA-Mood were, respectively, assessed as task-evoked changes in pain intensity, pressure pain threshold (back, hands), situational catastrophizing. Over the next 9 days, daily life pain and mood were assessed using smartphone-based ecological momentary assessment (EMA-Pain and EMA-Mood, respectively) with stratified random sampling. Data analyses estimated fixed effects (b) using multilevel linear modelling with random intercepts. RESULTS: Median EMA completion per participant was 66.67% (n = 67 participants). After controlling for covariates, SPA-Pain was associated with EMA-Pain (b = 0.235, p = 0.002) and SPA-Psych approached significance with EMA-Mood (b = -0.159, p = 0.052). CONCLUSIONS: Task-based assessment of SPA helps explain daily life pain and mood among adults with back pain, beyond traditional questionnaires. Adding task-based assessment of SPA may achieve a more complete picture of pain and mood in daily life, offering clinicians better guidance when prescribing activity-based interventions that are designed to modify daily life behaviour, such as graded activity. SIGNIFICANCE: This study found that, among people with back pain, task-based measures of sensitivity to physical activity contribute additional predictive value for daily life pain and mood beyond self-report questionnaires. Findings suggest that real-time, task-based measures may help mitigate some of the shortcomings that are commonly associated with retrospective questionnaires.

Molecular confirmation of primary monophasic synovial sarcoma of the mandible: diagnosis and management.

Synovial sarcoma (SS) is a rare, high-grade, soft tissue malignancy that originates from pluripotent mesenchymal stem cells. Knox introduced the term 'synovial sarcoma', noting its histological similarity to synovial tissue. SS is seen most frequently in young and middle-aged adults with an equal sex distribution. Symptoms are non-specific and relate to the local effect of the mass. Currently, we know of no specific guidelines for the management of SS in the head and neck. We report a case of primary monophasic SS of the mandible in a 59-year-old male, and outline our diagnostic approach and management.

Airway Epithelial Cells Drive Airway Smooth Muscle Cell Phenotype Switching to the Proliferative and Pro-inflammatory Phenotype.

The increased mass of airway smooth muscle (ASM) in the airways of asthmatic patients may contribute to the pathology of this disease by increasing the capacity for airway narrowing. Evidence for the airway epithelium as a participant in ASM remodeling is accruing. To investigate mechanisms by which airway epithelial cells induce ASM cell (ASMC) proliferation, we have employed a co-culture model to explore markers of ASMC proliferative phenotype. Co-culture with epithelial cells led to incorporation of bromodeoxyuridine into ASMCs, indicating augmented proliferation and an associated increase in mRNA of the pro-proliferative co-transcription factor Elk1. Although the mitogen heparin-binding epidermal growth factor (HB-EGF) was augmented in the co-culture supernatant, the ASMC epidermal growth factor receptor (EGFR), an effector of HB-EGF induced proliferation, did not mediate epithelial-induced proliferation. The co-culture increased the expression of ASMC mRNA for the pro-inflammatory cytokines IL-6 and IL-8 as well as the pro-proliferative microRNA miR-210. The transcriptional repressor Max-binding protein (Mnt), a putative target of miR-210, was transcriptionally repressed in co-cultured ASMCs. Together, these data indicate that the airway epithelium-induced proliferative phenotype of ASMCs is not driven by EGFR signaling, but rather may be dependent on miR210 targeting of tumor suppressor Mnt.

Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis.

BACKGROUND: Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta-analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. METHODS: The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age- and sex-matched cohorts. RESULTS: Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta-analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2  = 0 per cent). CONCLUSION: BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

ANTECEDENTES: Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20-40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA. MÉTODOS: Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo. RESULTADOS: No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80-1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)). CONCLUSIÓN: Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.

The Efficacy of Prophylactic Negative Pressure Wound Therapy for Closed Incisions in Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Negative pressure wound therapy (NPWT) is a promising advance in the management of closed surgical incisions. NPWT application induces several effects locally within the wound including reduced lateral tension and improving lymphatic drainage. As a result, NPWT may improve wound healing and reduce surgical site complications. We aim to evaluate the efficacy of prophylactic application of NPWT in preventing surgical site complications for closed incisions in breast surgery. METHODS: This systematic review was reported according to PRISMA guidelines. The protocol was published in PROSPERO (CRD42018114625). Medline, Embase, CINAHL and Cochrane Library databases were searched for studies which compare the efficacy of NPWT versus non-NPWT dressings for closed incisions in breast surgery. Specific outcomes of interest were total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. RESULTS: Seven studies (1500 breast incisions in 904 patients) met the inclusion criteria. NPWT was associated with a significantly lower rate of total wound complications [odds ratio (OR) 0.36; 95% CI 0.19-069; P = 0.002], SSI (OR 0.45; 95% CI 0.24-0.86; P = 0.015), seroma (OR 0.28; 95% CI 0.13-0.59; P = 0.001), wound dehiscence (OR 0.49; 95% CI 0.32-0.72; P < 0.001) and wound necrosis (OR 0.38; 95% CI 0.19-0.78; P = 0.008). There was no significant difference in haematoma rate (OR 0.8; 95% CI 0.19-3.2; P = 0.75). Statistically significant heterogeneity existed for total wound complications, but no other outcomes. CONCLUSION: Compared with conventional non-NPWT dressings, prophylactic application of NPWT is associated with significantly fewer surgical site complications including SSI, seroma, wound dehiscence and wound necrosis for closed breast incisions.

Health literacy and the perception of risk in a breast cancer family history clinic.

BACKGROUND: Informed consent is an essential component of medical practice, and especially so in procedural based specialties which entail varying degrees of risk. Breast cancer is one of the most common cancers in women, and as such is the focus of extensive research and significant media attention. Despite this, considerable misperception exists regarding the risk of developing breast cancer. AIMS: This study aims to examine the accuracy of risk perception of women attending a breast cancer family history clinic, and to explore the relationship between risk perception accuracy and health literacy. METHODS: A cross-sectional study of women attending a breast cancer family history clinic (n = 86) was carried out, consisting of a patient survey and a validated health literacy assessment. Patients' perception of personal and population breast cancer risk was compared to actual risk as calculated by a validated risk assessment tool. RESULTS: Significant discordance between real and perceived risks was observed. The majority (83.7%) of women overestimated their personal lifetime risk of developing breast cancer, as well as that of other women of the same age (89.5%). Health literacy was considered potentially inadequate in 37.2% of patients; there was a correlation between low health literacy and increased risk perception inaccuracy across both personal ten-year (rs = 0.224, p = 0.039) and general ten-year population estimations. (rs = 0.267, p = 0.013). CONCLUSION: Inaccuracy in risk perception is highly prevalent in women attending a breast cancer family history clinic. Health literacy inadequacy is significantly associated with this inaccuracy.

Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment.

AIM: To evaluate the use the distance between the adjacent septal nuclei as a surrogate marker of septal area atrophy seen in Alzheimer's disease (AD). MATERIALS & METHODS: Interseptal distance (ISD) was measured, blind to clinical details, in 250 patients who underwent computed tomography (CT) of the brain at University Hospital of Wales. Clinical details including memory problem history were retrieved. An ISD cut-off value that discriminated those with and without memory symptoms was sought. ISD measurements were also made in 20 AD patients. To test both the method and the defined cut-off, measurements were then made in an independent cohort of 21 mild cognitive impairment (MCI) patients and 45 age-matched healthy controls, in a randomised and blinded fashion. RESULTS: ISD measurement was achieved in all patients. In 28 patients with memory symptoms, the mean ISD was 5.9 mm compared with 2.3 mm in those without overt symptoms (p=0.001). The optimum ISD cut-off value was 4 mm (sensitivity 85.7% and specificity 85.8%). All AD patients had an ISD of >4 mm (mean ISD= 6.1 mm). The mean ISD for MCI patients was 3.84 mm compared with 2.18 mm in age-matched healthy controls (p=0.001). Using a 4 mm cut-off correctly categorised 10 mild cognitive impairment patients (47.6%) and 38 healthy controls (84.4%). CONCLUSION: ISD is a simple and reliable surrogate measurement for septal area atrophy, applicable to CT and magnetic resonance imaging (MRI). It can be used to help select patients for further investigation.

Expectancies mediate the relationship between perceived injustice and return to work following whiplash injury: A 1-year prospective study.

BACKGROUND: Emerging evidence suggests that perceived injustice is a risk factor for work disability in individuals with whiplash injury. At present, however, little is known about the processes by which perceived injustice impacts on return to work. The purpose of this study was to examine whether expectancies mediated the relationship between perceived injustice and return to work in patients with whiplash injury. METHOD: One hundred and fifty-two individuals (81 men, 71 women) with a primary diagnosis of whiplash injury completed self-report measures of pain intensity, perceived injustice and return-to-work expectancies following admission to a rehabilitation programme. Work status was assessed 1 year after discharge. RESULTS: Consistent with previous research, high scores on a measure of perceived injustice were associated with prolonged work disability. Results indicated that high perceptions of injustice were associated with low return-to-work expectancies. Causal mediation analyses revealed that expectancies fully mediated the relationship between perceived injustice and return to work. CONCLUSION: The findings suggest that intervention techniques designed to target expectancies could improve return-to-work outcomes in patients with whiplash injury. Discussion addresses the processes by which expectancies might impact on return-to-work outcomes and the manner in which negative return-to-work expectancies might be modified through intervention. SIGNIFICANCE: The study confirms that expectancies are the mechanism through which perceived injustice impacts return to work following whiplash injury. The findings suggest that interventions designed to specifically target return-to-work expectancies might improve rehabilitation outcomes in patients with whiplash injury.

Risk assessment in paediatric glioma-Time to move on from the binary classification.

BACKGROUND: Paediatric glioma encompasses a wide range of entities with highly variable prognoses. Gliomas are grouped by histopathological features into high- and low-grade glioma but this classification until recently has not taken into account many emerging risk factors in this disease. A comprehensive risk classification has not been published for paediatric glioma despite many risk factors being established in this disease. METHODS: A comprehensive literature review was carried out identifying risk factors for paediatric low-grade and high-grade glioma. RESULTS: The most consistently described risk factors in high-grade glioma included midline location and extent of surgical resection. For patients with progressive unresectable low-grade glioma, age under 1, neurofibromatosis type I status and location were the most consistently prognostic. Molecular classification shows promise in accurately reassigning diagnosis for some gliomas. CONCLUSION: Risk profiling in paediatric glioma will require a focused multinational effort but will result in a more accurate and nuanced assessment of prognosis.

The metabolic impact of extracellular nitrite on aerobic metabolism of Paracoccus denitrificans.

Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite/FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite/FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH-dependent manner that is likely to be a result of both nitrite and free nitrous acid (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established Fhp to be involved in endowing nitrite/FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as nitric oxide from the internalisation of FNA.

Faster Cancer Treatment: Using timestamp data to improve patient journeys.

This paper presents a case study of research conducted to improve the delivery of treatment to high priority cancer patients. The authors present a modelling framework that uses time-stamp data collected by the North Shore Hospital IT systems as "business as usual", to describe the patient journey through the cancer-care process. A simulation process is developed that uses this data to estimate the service's performance under current operating practices, and enables "what-if" analysis to identify where changes to current practice can most effectively be applied, ensuring the investment of additional resource can be targeted at the steps of the patient pathway where it can result in the greatest improvement. The process is illustrated using the Breast Cancer stream as a case-study, for the initial study period (July 2013 to June 2014), with a follow-up analysis presented briefly for the 3 months from July to the end of September 2014.

When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.

BACKGROUND: The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up. METHODS: A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. RESULTS: 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.

Endocrine therapy adherence: a cross-sectional study of factors affecting adherence and discontinuation of therapy.

BACKGROUND/AIMS: Adjuvant endocrine therapy for at least 5 years improves oncological outcomes in oestrogen receptor-positive breast cancer. Adherence rates to prescribed endocrine therapy are low and the search for modifiable causes of this continues. The aim of this study was to assess adherence rates in an Irish cohort of breast cancer patients prescribed adjuvant endocrine therapy and to assess modifiable factors associated with suboptimal adherence. METHODS: A cross-sectional anonymous survey was performed on 261 patients currently prescribed endocrine therapy. Data were collected regarding demographics, treatment, social and emotional factors and medication side effects. Each patient completed a medication adherence score and provided information about discontinuation of therapy and reasons for same. RESULTS: Only 67.8 % of patients assessed demonstrated complete medication adherence on the medication adherence scale. Twenty-nine patients (10.9 %) permanently stopped taking their prescribed endocrine therapy. Suboptimal adherence was more likely in younger patients (p < 0.001), those in employment (p = 0.005), those who experienced side effects (p = 0.006), those who perceived themselves to have low levels of emotional support (p < 0.001) and those who use the internet to read about their illness (p = 0.003). CONCLUSIONS: Endocrine therapy adherence is suboptimal in almost one-third of patients in our cohort. Appropriate assessment and management of side effects and negative emotions, combined with direction of patients to accurate internet sources of information, could help improve endocrine therapy adherence in women with early-stage breast cancer.

Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities.

Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically normal older adults, we tested whether the relationship between structural connectivity (via diffusion imaging tractography) and functional connectivity (via resting-state functional MRI) of the posterior cingulate cortex (PCC) and medial prefrontal frontal cortex (MPFC) of the DN was altered in the presence of white matter hyperintensities (WMH). A significant correlation was observed between microstructural properties of the cingulum bundle and MPFC-PCC functional connectivity in individuals with low WMH load, but not with high WMH load. No correlation was observed between PCC-MPFC functional connectivity and microstructure of the inferior longitudinal fasciculus, a tract not passing through the PCC or MPFC. Decoupling of connectivity, measured as the absolute difference between structural and functional connectivity, in the high WMH group was related to poorer executive functioning and memory performance. These results suggest that such decoupling may reflect reorganization of functional networks in response to global white matter pathology and may provide an early marker of clinically relevant network alterations.

An experimental investigation of the effect of a justice violation on pain experience and expression among individuals with high and low just world beliefs.

BACKGROUND: Perceptions of injustice are linked with poorer physical and psychological outcomes in the context of pain and injury. Violations of injustice can arise out of violations of just world belief (JWB). However, no study has yet examined whether JWB moderates the effect of justice violation on pain experience. METHODS: The current study examined the effect of an experimental justice violation on acute pain outcomes and whether JWB moderated this effect. Participants completed the JWB scale and then engaged in two cold pressor tasks (CPT). Half the participants were told that the second CPT immersion was part of standard protocol; the other half were told that the painful procedure had to be repeated due to experimenter negligence. Participants provided report of pain intensity following each CPT immersion. Video records of participants undergoing the CPT were coded for presence and duration of pain behaviour. RESULTS: Exposure to the justice violation resulted in elevated pain intensity from the first to the second immersion only among participants with high JWB. For participants with low JWB and participants in the control condition, there was no significant difference in pain intensity across immersions. Control participants showed a decrease in pain behaviour from the first to the second immersion. In the negligence/ justice violation condition, reductions in pain behaviour were observed only among participants with low JWB. CONCLUSIONS: Our results indicate that individuals with high JWB may show particularly adverse reactions in response to justice violations in the context of acute pain experience.

Neural processing of sensory and emotional-communicative information associated with the perception of vicarious pain.

The specific neural processes underlying vicarious pain perception are not fully understood. In this functional imaging study, 20 participants viewed pain-evoking or neutral images displaying either sensory or emotional-communicative information. The pain images displayed nociceptive agents applied to the hand or the foot (sensory information) or facial expressions of pain (emotional-communicative information) and were matched with their neutral counterparts. Combining pain-evoking and neutral images showed that body limbs elicited greater activity in sensory motor regions, whereas midline frontal and parietal cortices and the amygdala responded more strongly to faces. The pain-evoking images elicited greater activity than their neutral counterparts in the bilateral inferior frontal gyrus (IFG), the left inferior parietal lobule (IPL) and the bilateral extrastriate body area. However, greater pain-related activity was observed in the rostral IPL when images depicted a hand or foot compared to a facial expression of pain, suggesting a more specific involvement in the coding of somato-motor information. Posterior probability maps enabling Bayesian inferences further showed that the anterior IFG (BA 45 and 47) was the only region showing no intrinsic probability of activation by the neutral images, consistent with a role in the extraction of the meaning of pain-related visual cues. Finally, inter-individual empathy traits correlated with responses in the supracallosal mid/anterior cingulate cortex and the anterior insula when pain-evoking images of body limbs or facial expressions were presented, suggesting that these regions regulated the observer's affective-motivational response independent from the channels from which vicarious pain is perceived.

Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum.

PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.

Impacts of climate, host and landscape factors on Culicoides species in Scotland.

Culicoides biting midges (Diptera: Ceratopogonidae) vector a wide variety of internationally important arboviral pathogens of livestock and represent a widespread biting nuisance. This study investigated the influence of landscape, host and remotely-sensed climate factors on local abundance of livestock-associated species in Scotland, within a hierarchical generalized linear model framework. The Culicoides obsoletus group and the Culicoides pulicaris group accounted for 56% and 41%, respectively, of adult females trapped. Culicoides impunctatus Goetghebuer and C. pulicaris s.s. Linnaeus were the most abundant and widespread species in the C. pulicaris group (accounting for 29% and 10%, respectively, of females trapped). Abundance models performed well for C. impunctatus, Culicoides deltus Edwards and Culicoides punctatus Meigen (adjusted R(2) : 0.59-0.70), but not for C. pulicaris s.s. (adjusted R(2) : 0.36) and the C. obsoletus group (adjusted R(2) : 0.08). Local-scale abundance patterns were best explained by models combining host, landscape and climate factors. The abundance of C. impunctatus was negatively associated with cattle density, but positively associated with pasture cover, consistent with this species' preference in the larval stage for lightly grazed, wet rush pasture. Predicted abundances of this species varied widely among farms even over short distances (less than a few km). Modelling approaches that may facilitate the more accurate prediction of local abundance patterns for a wider range of Culicoides species are discussed.