iCanADAPT Early protocol: randomised controlled trial (RCT) of clinician supervised transdiagnostic internet-delivered cognitive behaviour therapy (iCBT) for depression and/or anxiety in early stage cancer survivors -vs- treatment as usual.

BACKGROUND: This RCT with two parallel arms will evaluate the efficacy of an internet-delivered transdiagnostic cognitive behavioural therapy (iCBT) intervention for the treatment of clinical depression and/or anxiety in early stage cancer survivors. METHODS/DESIGN: Early stage cancer survivors will be recruited via the research arm of a not-for-profit clinical research unit and randomised to an intervention (iCBT) group or a 'treatment as usual' (TAU) control group. The minimum sample size for each group is 45 people (assuming effect size > 0.6, power of 80%, and alpha at .05), but 10% more will be recruited to account for attrition. A solitary or cumulative diagnosis(es) of Major Depressive Episode (current), Generalised Anxiety Disorder, Illness Anxiety Disorder, Panic Disorder, Agoraphobia, and/or Adjustment disorder will be determined using modules from the Anxiety Disorders Interview Schedule for DSM-5. Depression and anxiety levels with be measured via the total score of the Hospital Anxiety and Depression scale (HADS-T), the primary outcome measure. Secondary measures will include the Kessler 10 to measure general distress, the Fear of Cancer Recurrence Inventory (FCRI) to measure the specific fear of cancer recurrence and the Functional Assessment of Cancer Therapy, General Version 4 (FACT-G) for self-report of physical, social, emotional and functional well-being. iCBT participants will complete the measures before lessons 1 and 5, at post-treatment and at 3-month follow-up. The TAU group will complete similar measures at weeks 1, 8 and 16 of the waiting period. Program efficacy will be determined using intent-to-treat mixed models. Maintenance of gains will be assessed at 3-month follow-up. Mediation analyses using PROCESS will be used to examine the association between change in depressive and anxious symptoms over time and changes in FCRI and FACT-G QOL in separate analysis. DISCUSSION: This is the first RCT looking at iCBT specifically for clinical depression and/or anxiety in a cancer population. Findings will help to direct the role of iCBT in streamlined psycho-social care pathways. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616000231448, registered 19th February 2016 ( www.anzctr.org.au ). This trial protocol is in compliance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.

e-TC: Development and pilot testing of a web-based intervention to reduce anxiety and depression in survivors of testicular cancer.

e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study.

Heterogeneity of HIV incidence: a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control.

OBJECTIVES: To describe HIV heterogeneity in rural Uganda using incidence data collected between January 2012 and December 2014 among fishing cohort (FC) and in an adjacent rural general population cohort (GPC). METHODS: In the FC, eligible HIV high-risk adults aged 18+ years were enrolled, followed and HIV tested every 3 months. Demographic and sexual behaviour data were also collected. The GPC, approximately 47 km away from the FC, was followed through annual surveys, and sociodemographic and behavioural data collected. A subset of GPC with comparable risk profiles to the FC was selected. We presented sociodemographic and risk profiles and also computed stratified HIV incidence. Cox regression was used to assess factors associated with HIV incidence. RESULTS: Overall HIV incidence was higher in the FC than in the 'high-risk' GPC, 6.04 and 0.56 per 100 person years at risk, respectively, with a rate ratio (RR) of 10.83 (95% CI 6.11 to 19.76). This was higher among those aged 18-24 years, unmarried and those with more than two sex partners in the past year, RR of 15.44, 22.99 and 19.29, respectively. In the FC, factors associated with high incidence in multivariate analysis were duration in the community and unprotected sex. The factors in the GPC were ethnicity, marital status and duration in the community. CONCLUSIONS: We have observed a substantial heterogeneity in HIV incidence. The high incidence in fishing communities is contributing greatly to the overall HIV burden in Uganda, and thus urgent combination prevention efforts are needed towards national goal to reduce HIV epidemic.

Physical symptoms, coping styles and quality of life in recurrent ovarian cancer: a prospective population-based study over the last year of life.

OBJECTIVE: The aim of this study was to describe the trajectory of physical symptoms, coping styles and quality of life (QoL) and the relationship between coping and QoL over the last year of life in women with recurrent ovarian cancer. METHODS: The patient cohort were women recruited to the Australian Ovarian Cancer Study who subsequently experienced recurrent, invasive ovarian cancer and completed at least one psychosocial assessment (optimism, minimisation, hopelessness/helplessness, QoL) during the last year of life (n=217). RESULTS: QoL declined sharply from six months before death. Lack of energy was the most prevalent symptom over three measurement periods (67-92%) and also the most severe. Anorexia (36-55%), abdominal swelling (33-58%), nausea (26-47%) and pain (26-43%) all increased in prevalence and severity towards the end of life. Higher optimism (p=0.009), higher minimisation (p=0.003) and lower helplessness/hopelessness (p=0.03) at baseline were significant predictors of subsequent higher QoL. CONCLUSIONS: Progressive deterioration in quality of life may be an indicator of death within about six months and therefore should be an important consideration in decisions about subsequent treatment. Coping styles which independently predicted subsequent changes in QoL could potentially be targeted by interventions to minimise worsening QoL.

A comparison of the FACT-G and the Supportive Care Needs Survey (SCNS) in women with ovarian cancer: unidimensionality of constructs.

PURPOSE: Health-related quality of life (HRQoL) and unmet needs (needs) questionnaires offer alternative perspectives for assessing cancer patients' concerns. We examined whether the conceptual differences underlying these alternative approaches yield corresponding empirical differences. METHODS: Eight-hundred and seventy-four women with ovarian cancer completed the Functional Assessment of Cancer Therapy scale (FACT-G; HRQoL) and the Supportive Care Needs Survey (SCNS-SF34; needs) every 3 months for 2 years. Correlational analysis, exploratory and confirmatory factor analysis (EFA/CFA), and Rasch analysis tested the relationship between patients' responses to similar domains and similar items across the two questionnaires. RESULTS: Strong correlations were found between items with virtually identical wording (0.67-0.75), while moderate to strong correlations (0.55-0.65) were found for those with very similar wording. EFA identified two common domains across the two questionnaires: physical and psychological. For each common domain, CFA indicated models involving a single construct with systematic variation within each questionnaire fit best. Rasch analysis including very similar items within the physical and psychological domains (separately) demonstrated strong evidence of unidimensionality. CONCLUSIONS: The high degree of similarity between patient responses to items addressing the same or very similar concerns suggests either that HRQoL and needs approaches do not reflect different constructs or that patients may not be able to differentiate between the severity of a concern and the level of need associated with that concern, especially when these are assessed in quick succession.

Choosing between the EORTC QLQ-C30 and FACT-G for measuring health-related quality of life in cancer clinical research: issues, evidence and recommendations.

BACKGROUND: This review aims to assist cancer clinical researchers in choosing between the two most widely used measures of cancer-specific health-related quality of life: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Functional Assessment of Cancer Therapy-General (FACT-G). MATERIALS AND METHODS: Information on QLQ-C30 and FACT-G content, scale structure, accessibility and availability was collated from websites and manuals. A systematic review was undertaken to identify all articles reporting on psychometric properties and information to assist interpretability. Evidence for reliability, validity and responsiveness was rated using a standardised checklist. Instrument properties were compared and contrasted to inform recommendations. RESULTS: Psychometric evidence does not recommend one questionnaire over the other in general. However, there are important differences between the scale structure, social domains and tone that inform choice for any particular study. CONCLUSIONS: Where research objectives are concerned with the impact of a specific tumour type, treatment or symptom, choice should be guided by the availability, content, scale structure and psychometric properties of relevant European Organisation for the Research and Treatment of Cancer versus Functional Assessment of Chronic Illness Therapy modules. Because the FACT-G combines symptoms and concerns within each scale, individual items should always be reviewed within the context of specific research objectives. Where these issues are indecisive, researchers are encouraged to use an algorithm at the end of the current article.

GSK2245035, a TLR7 agonist, Does Not Increase Pregnancy Loss in Cynomolgus Monkeys.

GSK2245035, a small molecule Toll-like Receptor 7 (TLR7) agonist developed for immunomodulatory treatment for allergic airways disease, aimed to reduce Th2 and enhance Th1/Treg responses to aeroallergens via the local induction of type I interferons (IFNs). GSK2245035 demonstrated selectivity for potent release of type I IFNs compared to TNF-α and IL-6, with dose dependent increases in the interferon inducible chemokine, IP-10, in the nasal compartment. Implantation and parturition require pro-inflammatory processes including IFNs, Interferon Stimulated Genes, TNFα and IP-10 while pregnancy requires immune regulation to maintain maternal fetal immune tolerance, and recombinant type I IFNs induced abortions in monkeys. Due to its mechanism of action, GSK2245035 was studied at pharmacologically and clinically relevant doses in a monkey pregnancy model. Monkeys received 0, 3 or 30 ng/kg/week GSK2245035 intranasally once weekly, from Day 20 postcoitum through Day 63 postpartum. Although systemic IFN-α and IP-10 levels were approximately 14.8 or 40 -fold (respectively) above predose levels at 3 or 30 ng/kg/week, respectively, there were no effects on pregnancy and infant outcome. Non-adverse effects included increased incidence of nasal discharge, increased maternal body temperature at 30 ng/kg/week and dose-dependent increases in maternal IP-10 and IFN-α and decreased infant anti-KLH IgM and IgG titers following KLH immunization at ≥3 ng/kg/week, relative to controls. Potentially, lower IFN-α and IP-10 levels as well as once-weekly intranasal dosing vs daily subcutaneous or intramuscular dosing with recombinant type I IFNs could explain the lack of pregnancy effects; however, there was an undesired impact on offspring immune function.

Smog aerosol: infrared spectra.

Infrared spectra of smog aerosol are similar to those of sulfuric acid aerosol, but they do not show the prominent CH and carbonyl bands of organic aerosols from terpenes. Some features of the smog aerosol spectra are not present in the spectra from either type of synthetic aerosol.

Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa.

OBJECTIVES: To demonstrate the value of routine, basic sexually transmitted infection (STI) screening at enrolment into an HIV-1 vaccine feasibility cohort study and to highlight the importance of soliciting a history of receptive anal intercourse (RAI) in adults identified as "high risk". METHODS: Routine STI screening was offered to adults at high risk of HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviours and STI prevalence were summarised and the value of microscopy assessed. Associations between prevalent HIV-1 infection and RAI or prevalent STI were evaluated with multiple logistic regression. RESULTS: Participants had a high burden of untreated STI. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. RAI was reported by 36% of male and 18% of female participants. RAI was strongly associated with HIV-1 in men (adjusted odds ratio (aOR) 3.8; 95% CI 2.0 to 6.9) and independently associated with syphilis in women (aOR 12.9; 95% CI 3.4 to 48.7). CONCLUSIONS: High-risk adults recruited for HIV-1 prevention trials carry a high STI burden. Symptom-directed treatment may miss many cases and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. STI screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk of HIV-1 acquisition.

Approach for gait analysis in persons with limb loss including residuum and prosthesis socket dynamics.

Musculoskeletal modeling and marker-based motion capture techniques are commonly used to quantify the motions of body segments, and the forces acting on them during human gait. However, when these techniques are applied to analyze the gait of people with lower limb loss, the clinically relevant interaction between the residual limb and prosthesis socket is typically overlooked. It is known that there is considerable motion and loading at the residuum-socket interface, yet traditional gait analysis techniques do not account for these factors due to the inability to place tracking markers on the residual limb inside of the socket. In the present work, we used a global optimization technique and anatomical constraints to estimate the motion and loading at the residuum-socket interface as part of standard gait analysis procedures. We systematically evaluated a range of parameters related to the residuum-socket interface, such as the number of degrees of freedom, and determined the configuration that yields the best compromise between faithfully tracking experimental marker positions while yielding anatomically realistic residuum-socket kinematics and loads that agree with data from the literature. Application of the present model to gait analysis for people with lower limb loss will deepen our understanding of the biomechanics of walking with a prosthesis, which should facilitate the development of enhanced rehabilitation protocols and improved assistive devices.

Control Points To Reduce Movement of Central Nervous System Tissue during Beef Slaughter.

Consumption of central nervous system tissue (CNST) from cattle with bovine spongiform encephalopathy (BSE) is thought to cause the human neurological disease, variant Creutzfeldt-Jacob disease. To identify points of cross-contamination of beef carcasses with CNST, 55 young beef cattle were slaughtered and processed through a federally inspected multispecies abattoir. The objectives of this study were to evaluate CNST spread following the placement of a plug in the penetration site of the skull after captive bolt stunning, to evaluate cross-contamination of carcasses before and after splitting, to compare the effects of hot water pasteurization (84°C for 10 s) versus cold water wash (10°C for 30 s) for reducing CNST on the carcass, and to examine other possible sources of cross-contamination in the abattoir. Results indicated that the use of a plastic plug reduced CNST contamination near the bolt penetration site. This study also confirmed that carcass splitting resulted in an increase in CNST contamination at various areas of the carcass. Hot water pasteurization appeared to be an effective means of removing CNST contamination from carcasses in most of the areas sampled.

A mapping method for the description of Warner-Bratzler shear force gradients in beef Longissimus thoracis et lumborum and Semitendinosus.

A novel approach to mapping Warner-Bratzler shear of whole muscles was explored. The procedure was used on the Longissimus thoracis et lumborum (LTL) and Semitendinosus (ST) from six beef cattle by first marking skeletally defined anatomical landmarks on the muscle in situ. After removal from the carcass, further divisions were made while preserving sample orientation during cooking and preparation for shearing. Shear gradients were observed in all planes of the LTL, particularly the medial-lateral. The mid-section of the ST had the lowest shears while superficial locations of the cross-section had greater values. Muscle comparison indicated the ST was more uniform than the LTL. The mapping technique was subsequently used to identify localized effects of altered carcass suspension on shear values and sarcomere length in the lumbar Longissimus from four beef cattle. This mapping method will provide guidance for further intensive investigation across the carcass musculature and under varying carcass conditions.

Cell calcium in human peripheral blood lymphocytes and the effect of mitogen.

The apparent cell concentration of calcium in human peripheral blood lymphocytes is 143.3 +/- 17.7 microM, as measured by two different techniques using 45Ca. The steady-state level of accumulation, and possibly the rate of uptake, are increased in the presence of succinyl-concanavalin A. Initiation of the mitogen-induced alteration of cell calcium occurs within 1-2 min and the change is complete within 5-10 min. Determinations of cell calcium in cells suspended in low Na media indicate that (1) there is no difference in cell calcium between cells incubated in 142 mM extracellular Na and cells incubated in 63 mM extracellular Na, and (2) the mitogen-induced increase in cell calcium is unaffected by a decrease in extracellular sodium concentration (to 63 mM).

Enhancement of parathyroid hormone-stimulated bone resorption by poly-L-lysine.

Poly-L-lysine (PL II; mol wt, 1000-4000) was added to fetal rat bones cultured in a chemically defined medium (BGJ) containing bovine serum albumin in the presence and absence of parathyroid hormone (PTH). Bone resorption was measured by the release of previously incorporated 45Ca. The addition of PL II at concentrations of 3-100 microgram/ml enhanced the stimulation of bone resorption by submaximal doses of PTH but had little effect on 45Ca release from control unstimulated cultures. Higher concentrations of PL II produced inhibition of 45Ca release. Dialysis of PL II did not alter enhancement or inhibition by PL II. PL II did not increase sensitivity to PTH in serum-supplemented cultures. Higher molecular weight PL II preparations were less effective. PL II did not enhance the resorptive response to 1,25-dihydroxyvitamin D, prostaglandin E2, osteoclast-activating factor, or bacterial endotoxin. The mechanism of the selective ability of PL II to enhance the response to low concentrations of PTH is unknown but may be due to the ability of this basic polypeptide to interfere with binding of PTH to sites other than the hormone receptor or to block degradation of PTH by bone.

Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS.

Muscarinic autoreceptors of the M2 subclass were examined in rat forebrain using a number of different methodologies, including receptor autoradiography and image analysis, regulation of acetylcholine release, phosphoinositide turnover, low-Km GTP hydrolysis, and behavioral analysis. The relatively minor population of M2 receptors in coronal sections was visualized by autoradiography and image analysis using [3H]quinuclidinyl benzilate in the presence of a concentration of pirenzepine that blocked most of M1 (and M4) receptors. The highest densities of M2 receptors in forebrain regions were found in the outer layers of the cortex, CA1 region of the hippocampus and striatum. The M2-, but not M1-selective antagonists were able to block the oxotremorine-induced attenuation of acetylcholine release in forebrain synaptosomes. Low concentrations of the M2-selective antagonist gallamine increased phosphoinositide turnover, which is thought to be an M1 postsynaptic response in the forebrain, in brain slices by a Ca2(+)-dependent mechanism. The M2-selective agonist oxotremorine produced a substantial stimulation of low-Km GTPase in cortical membranes, suggesting that M2 forebrain receptors are efficiently coupled to G-proteins in the cortex. Behavioral signs of cholinergic stimulation were observed after intracerebroventricular injections of M2-, but not M1-selective antagonists. It is suggested that a minor population of forebrain M2 receptors regulates acetylcholine release by a mechanism that includes coupling through G-proteins presynaptically at synapses for which the postsynaptic response involves phosphoinositide turnover. Selective blockade of these receptors produces both biochemical and behavioral signs of acetylcholine release.

Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer.

OBJECTIVE: Review empirical evidence for a relationship between psychosocial factors and breast cancer development. METHODS: Standardised quality assessment criteria were utilised to assess the evidence of psychosocial predictors of breast cancer development in the following domains: (a) stressful life events, (b) coping style, (c) social support, and (d) emotional and personality factors. RESULTS: Few well-designed studies report any association between life events and breast cancer, the exception being two small studies using the Life Events and Difficulties Schedule (LEDS) reporting an association between severely threatening events and breast cancer risk. Seven studies show anger repression or alexithymia are predictors, the strongest evidence suggesting younger women are at increased risk. There is no evidence that social support, chronic anxiety, or depression affects breast cancer development. With the exception of rationality/anti-emotionality, personality factors do not predict breast cancer risk. CONCLUSION: The evidence for a relationship between psychosocial factors and breast cancer is weak. The strongest predictors are emotional repression and severe life events. Future research would benefit from theoretical grounding and greater methodological rigour. Recommendations are given.

The injured canine cervical spine after six months of healing. An in vitro three-dimensional study.

The cervical spine is a common site of spinal injuries. The stability of an injured cervical spine is not only dependent on injury severity, but also on the degree of healing time. Using a canine model, three injuries of varying degrees of severity were surgically produced at the C4-C5 level and allowed to heal for 6 months. No internal or external support was provided. The harvested cervical spines (C2-C7) were subjected to three-dimensional biomechanical testing by applying individually six pure moments. The resulting three-dimensional displacements were recorded using stereophotogrammetry, and the intervertebral motions were calculated. The results are compared with the in vivo behavior of the same specimens and with an in vitro control group. At 1 N-m, the average flexion-extension range of motion (ROM) for the intact C4-C5 level was 24.5 degrees (standard deviation [SD], 6.6 degrees). A facetectomy at this level significantly increased the in vitro ROM to 51.1 degrees (SD, 4.4 degrees). The in vitro ROM decreased to 19.8 degrees (SD, 7.3 degrees) in the facetectomized group of this study, which were allowed to heal for 6 months before death. Similar results were obtained in axial rotation and lateral bending. The findings show that after 6 months of healing, the injured canine spine, although acutely hypermobile, exhibited biomechanical characteristics that were not different from those of the normal intact specimens.

Plasma growth hormone and insulin concentrations in double-muscled and normal bull calves.

Blood samples were taken from 19 double-muscled (DM) and 20 normal (N) bull calves at the ages of 1.5, 2, 2.5, 3, 3.5, 4, 5.5, 6.5 and 9 mo to compare the plasma concentrations of growth hormone and insulin in DM with those in N bull calves and to relate these to differences in growth rate between the two breed groups. Double-muscled bull calves were lighter (P less than .0001) than N calves at all ages and had lower (P less than .001) preweaning and postweaning rates of gain. Double-muscled bull calves had lower (P less than .01) mean growth hormone concentration than N calves. Mean growth hormone concentration was correlated positively with body weight and preweaning rate of gain. The effect of age on growth hormone concentration was linear (P less than .05); however, mean growth hormone concentration fluctuated between ages 1.5 to 4.5 mo but stabilized after 5.5 mo of age in both breed groups. Mean insulin concentration was lower (P less than .01) in DM than in N bull calves. The effect of age on insulin concentration was both linear and quadratic (P less than .0001). Mean insulin concentration generally was constant in both breed groups, at around .75 ng/ml, from 1.5 to 6.5 mo of age but rose sharply to around 1.67 ng/ml after weaning when the bulls were put on a high-energy diet.

Heterosis, maternal and direct effects in double-muscled and normal cattle: I. Reproduction and growth traits.

Data from a two-breed group diallel experiment involving double-muscled (DM) and normal (N) cattle were analyzed to evaluate the importance of heterosis, maternal and direct effects for reproduction and growth traits. The DM cattle were from a composite of primarily Angus, Charolais, Galloway and Hereford breeds, and N cattle were crossbred cattle with at least 50% Hereford breeding. The data comprised a total of 491 matings and 389 calvings in four breeding seasons. Records on calving performance, calving date, calf crop born and weaned, sex ratio of progeny and weight of calves were analyzed using least squares procedures. Significant heterosis of 5 to 12% was observed for all the calf crop and growth traits, except for birth weight. Heterosis resulted in 24% reduction in the incidence of dystocia and perinatal calf mortality (P less than .05). The significant heterosis was due mainly to poor production in DM X DM crosses. The DM cows were superior (P less than .05) to N cows in reciprocal crossing (maternal effect) for all the calf crop traits, but had higher incidence of calving difficulty and a higher proportion of male progeny. Significant direct effect was observed for all the traits except calving date and sex ratio among progeny. The N sires were superior for all the calf crop traits and caused less incidence of dystocia and perinatal mortality compared with the DM sires. Significant differences were obtained between the straightbreds for all the traits except calving date. The N straightbreds were superior to the DM straightbreds for all the significant traits.