Adolescent depression and the family : a paradox

Discusses the role of the family in the development, treatment and prevention of adolescent depression. Studies have demonstrated that between 21–32% of adolescents report mild to severe symptoms of depression. The research points out the need for increased attention to adolescent depression because of its high prevalence, the risk factor for the development of other disorders and suicide, recurrence and tendency to endure into adulthood. Many studies have shown a strong relationship between depressive symptomatology and family factors. Therefore, family interventions should play an important role in the prevention and treatment of adolescent depression. However, there exists a paradox in that the research published to date fails to show that family-intervention programs add to the efficacy of treatments provided to the adolescents. Possible explanations for this paradox are discussed.

Do anti-inflammatory agents promote linear ablation lesion discontinuities? : an electrophysiological examination

Background: Catheter ablation for atrial fibrillation (AF) is more efficacious than antiarrhythmic therapy. Post ablation recurrences reduce ablation effectiveness and are contributed by lesion discontinuity in the fibrotic linear ablation lesions. The anti-fibrotic role of statins in reducing AF is being assessed in current trials. By reducing the chronic pathological fibrosis that occurs in AF they may reduce AF. However if statins also have an effect on the acute therapeutic fibrosis of an ablation, this could exacerbate lesion discontinuity and AF recurrence. We tested the hypothesis that statins attenuate ablation lesion continuity in a recognised pig atrial linear ablation model. Aims: To assess whether Atorvastatin diminishes the bi-directional conduction block produced by a linear atrial ablation lesion. Methods: Sixteen pigs were randomised to statin (n=8) or placebo (n=8) with drug pre-treatment for 3 days and a further 4 weeks. At initial electrophysiological study (EPS1) 3D right atrium (RA) mapping and a vertical ablation linear lesion in the posterior RA with bidirectional conduction block were completed (Gepstein Circ 1999). Follow-up electrophysiological assessment (EPS2) at 28 days assessed bidirectional conduction block maintenance. Results: Data of 15/16 (statin=7) pigs were analysed. Mean lesion length was 3.7 ± 0.8cm with a mean of 17.9 ± 5.7 lesion applications. Bi-directional conduction block was confirmed in 15/15 pigs (100%) at EPS1 and EPS2. Conclusions: Atorvastatin did not affect ablation lesion continuity in this pig atrial linear ablation model. If patients are on long-term statins for AF reduction, periablation cessation is probably not necessary.

A multilevel investigation of inequalities in clinical and psychosocial outcomes for women after breast cancer

Background In Australia, breast cancer is the most common cancer affecting Australian women. Inequalities in clinical and psychosocial outcomes have existed for some time, affecting particularly women from rural areas and from areas of disadvantage. We have a limited understanding of how individual and area-level factors are related to each other, and their associations with survival and other clinical and psychosocial outcomes. Methods/Design This study will examine associations between breast cancer recurrence, survival and psychosocial outcomes (e.g. distress, unmet supportive care needs, quality of life). The study will use an innovative multilevel approach using area-level factors simultaneously with detailed individual-level factors to assess the relative importance of remoteness, socioeconomic and demographic factors, diagnostic and treatment pathways and processes, and supportive care utilization to clinical and psychosocial outcomes. The study will use telephone and self-administered questionnaires to collect individual-level data from approximately 3, 300 women ascertained from the Queensland Cancer Registry diagnosed with invasive breast cancer residing in 478 Statistical Local Areas Queensland in 2011 and 2012. Area-level data will be sourced from the Australian Bureau of Statistics census data. Geo-coding and spatial technology will be used to calculate road travel distances from patients' residence to diagnostic and treatment centres. Data analysis will include a combination of standard empirical procedures and multilevel modelling. Discussion The study will address the critical question of: what are the individual- or area-level factors associated with inequalities in outcomes from breast cancer? The findings will provide health care providers and policy makers with targeted information to improve the management of women with breast cancer, and inform the development of strategies to improve psychosocial care for women with breast cancer.

Expression of PTRF in PC3 cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways

Expression of caveolin-1 is up-regulated in prostate cancer metastasis and is associated with aggressive recurrence of the disease. Intriguingly, caveolin-1 is also secreted from prostate cancer cell lines and has been identified in secreted prostasomes. Caveolin-1 is the major structural component of the plasma membrane invaginations called caveolae. Co-expression of the coat protein Polymerase I and transcript release factor (PTRF) is required for caveolae formation. We recently found that expression of caveolin-1 in the aggressive prostate cancer cell line PC-3 is not accompanied by PTRF, leading to noncaveolar caveolin-1 lipid rafts. Moreover, ectopic expression of PTRF in PC-3 cells sequesters caveolin-1 into caveolae. Here we quantitatively analyzed the effect of PTRF expression on the PC-3 proteome using stable isotope labeling by amino acids in culture and subcellular proteomics. We show that PTRF reduced the secretion of a subset of proteins including secreted proteases, cytokines, and growth regulatory proteins, partly via a reduction in prostasome secretion. To determine the cellular mechanism accounting for the observed reduction in secreted proteins we analyzed total membrane and the detergent-resistant membrane fractions. Our data show that PTRF expression selectively impaired the recruitment of actin cytoskeletal proteins to the detergent-resistant membrane, which correlated with altered cholesterol distribution in PC-3 cells expressing PTRF. Consistent with this, modulating cellular cholesterol altered the actin cytoskeleton and protein secretion in PC-3 cells. Intriguingly, several proteins that function in ER to Golgi trafficking were reduced by PTRF expression. Taken together, these results suggest that the noncaveolar caveolin-1 found in prostate cancer cells generates a lipid raft microenvironment that accentuates secretion pathways, possibly at the step of ER sorting/exit. Importantly, these effects could be modulated by PTRF expression.

Knee flexor strength and biceps femoris activation deficits following hamstring strain injury

Background: Hamstring strain injuries (HSI) are prevalent in sport and re-injury rates have been high for many years. Maladaptation following HSI are implicated in injury recurrence however nervous system function following HSI has received little attention. Aim: To determine if recreational athletes with a history of unilateral HSI, who have returned to training and competition, will exhibit lower levels of voluntary activation (VA) and median power frequency (MPF) in the previously injured limb compared to the uninjured limb at long muscle lengths. Methods: Twenty-eight recreational athletes were recruited. Of these, 13 athletes had a history of unilateral HSI and 15 had no history of HSI. Following familiarisation, all athletes undertook isokinetic dynamometry testing and surface electromyography assessment of the biceps femoris long head and medial hamstrings during concentric and eccentric contractions at ± 180 and ± 60deg/s. Results: The previously injured limb was weaker at all contraction speeds compared to the uninjured limb (+180deg/s mean difference(MD) = 9.3Nm, p = 0.0036; +60deg/s MD = 14.0Nm, p = 0.0013; -60deg/s MD = 18.3Nm, p = 0.0007; -180deg/s MD = 20.5Nm, p = 0.0007) whilst VA was only lower in the biceps femoris long head during eccentric contractions (-60deg/s MD = 0.13, p = 0.0025; -180deg/s MD = 0.13, p = 0.0003). There were no between limb differences in medial hamstring VA or MPF from either biceps femoris long head or medial hamstrings in the injured group. The uninjured group showed no between limb differences with any of the tested variables. Conclusion: Previously injured hamstrings were weaker than the contralateral uninjured hamstring at all tested speeds and contraction modes. During eccentric contractions biceps femoris long head VA was lower in the previously injured limb suggesting neural control of biceps femoris long head may be altered following HSI. Current rehabilitation practices have been unsuccessful in restoring strength and VA following HSI. Restoration of these markers should be considered when determining the success of rehabilitation from HSI. Further investigations are required to elucidate the full impact of lower levels of biceps femoris long head VA following HSI on rehabilitation outcomes and re-injury risk.

Kallikrein 14 is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

Psychosocial experience of cancer : surpassing mere survival and recognising the potential for posttraumatic growth as well as distress.

The publication of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) introduced the notion that a life-threatening illness can be a stressor and catalyst for Posttraumatic Stress Disorder (PTSD). Since then a solid body of research has been established investigating the post-diagnosis experience of cancer. These studies have identified a number of short and long-term life changes resulting from a diagnosis of cancer and associated treatments. In this chapter, we discuss the psychosocial response to the cancer experience and the potential for cancer-related distress. Cancer can represent a life-threatening diagnosis that may be associated with aggressive treatments and result in physical and psychological changes. The potential for future trauma through the lasting effects of the disease and treatment, and the possibility of recurrence, can be a source of continued psychological distress. In addition to the documented adverse repercussions of cancer, we also outline the recent shift that has occurred in the psycho-oncology literature regarding positive life change or posttraumatic growth that is commonly reported after a diagnosis of cancer. Adopting a salutogenic framework acknowledges that the cancer experience is a dynamic psychosocial process with both negative and positive repercussions. Next, we describe the situational and individual factors that are associated with posttraumatic growth and the types of positive life change that are prevalent in this context. Finally, we discuss the implications of this research in a therapeutic context and the directions of future posttraumatic growth research with cancer survivors. This chapter will present both quantitative and qualitative research that indicates the potential for personal growth from adversity rather than just mere survival and return to pre-diagnosis functioning. It is important to emphasise however, that the presence of growth and prevalence of resilience does not negate the extremely distressing nature of a cancer diagnosis for the patient and their families and the suffering that can accompany treatment regimes. Indeed, it will be explained that for growth to occur, the experience must be one that quite literally shatters previously held schemas in order to act as a catalyst for change.

Health service pathways for patients with chronic leg ulcers : identifying effective pathways for facilitation of evidence based wound care

Background: Chronic leg ulcers cause long term ill-health for older adults and the condition places a significant burden on health service resources. Although evidence on effective management of the condition is available, a significant evidence-practice gap is known to exist, with many suggested reasons e.g. multiple care providers, costs of care and treatments. This study aimed to identify effective health service pathways of care which facilitated evidence-based management of chronic leg ulcers. Methods: A sample of 70 patients presenting with a lower limb leg or foot ulcer at specialist wound clinics in Queensland, Australia were recruited for an observational study and survey. Retrospective data were collected on demographics, health, medical history, treatments, costs and health service pathways in the previous 12 months. Prospective data were collected on health service pathways, pain, functional ability, quality of life, treatments, wound healing and recurrence outcomes for 24 weeks from admission. Results: Retrospective data indicated that evidence based guidelines were poorly implemented prior to admission to the study, e.g. only 31% of participants with a lower limb ulcer had an ABPI or duplex assessment in the previous 12 months. On average, participants accessed care 2–3 times/week for 17 weeks from multiple health service providers in the twelve months before admission to the study clinics. Following admission to specialist wound clinics, participants accessed care on average once per week for 12 weeks from a smaller range of providers. The median ulcer duration on admission to the study was 22 weeks (range 2–728 weeks). Following admission to wound clinics, implementation of key indicators of evidence based care increased (p<0.001) and Kaplan-Meier survival analysis found the median time to healing was 12 weeks (95% CI 9.3–14.7). Implementation of evidence based care was significantly related to improved healing outcomes (p<0.001). Conclusions: This study highlights the complexities involved in accessing expertise and evidence based wound care for adults with chronic leg or foot ulcers. Results demonstrate that access to wound management expertise can promote streamlined health services and evidence based wound care, leading to efficient use of health resources and improved health.

A randomized controlled pilot study comparing aqueous cream with a beeswax and herbal oil cream in the provision of relief from postburn pruritis

Postburn itch is reported to affect up to 87% of the burn population. Although treatments for postburn itch are multimodal, they remain consistently ineffective. However, recent anecdotal evidence from several outpatients at a tertiary referral hospital suggests that a cream combining beeswax and several herbal oils may be effective in the minimization of postburn itch. The aim of this study was to test the efficacy of beeswax and herbal oil cream against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. A randomized controlled trial compared two groups using a visual analog scale, frequency of cream application, itch recurrence after cream application, use of antipruritic medications, and sleep disturbance to determine the effect of itch severity and duration. Fifty-two participants were enrolled in the study (84% male) with a mean age of 35 years (SD = 16) and mean burn TBSA of 7.2% (SD = 7.7). Study results found that the beeswax and herbal oil cream reduce itch after application more frequently than aqueous cream (P = .001). In addition, when managed with beeswax and herbal oil cream, participants found that their itch recurred later (P ≤ .001) and their use of antipruritic medications was lower (P = .023). Findings of this study suggest beeswax and herbal oil cream to be more effective in the minimization of postburn itch than aqueous cream. Given this, a larger study examining the efficacy of beeswax and herbal oil cream appears warranted.

The largest eruptions in Earth's history

Large igneous provinces (LIPs) host the most frequently recurring, largest volume basaltic & silicic eruptions on Earth. The largest volume (>1000 km^3 DRE) and magnitude (>M8) eruptions produce areally extensive (10^4-10^5 km^2) basaltic flow fields and sills, and silicic ignimbrites that are the main LIP building blocks. Basaltic and silicic eruptions have comparable magnitudes, but silicic ignimbrite volumes may be significantly underestimated due to unrecognized and correlated, but voluminous co-ignimbrite ash deposits. Magma composition is no barrier to individual eruption volume. Despite similar magnitudes, flood basaltic and silicic eruptions are very different in eruption mechanism, duration, intensity, vent configuration, and emplacement style. Flood basalts are dominantly effusive Hawaiian-Strombolian, with magma discharge rates of ~10^7-10^8 kg s^-1, and produce dominantly compound pahoehoe flow fields over eruption durations most likely >10 yrs. Most silicic eruptions are moderately to highly explosive, producing cocurrent pyroclastic fountains (rarely Plinian) and suggested to be of short-duration (hours to days) and high intensity (~10^11 kg s^-1). Eruption frequencies are elevated for largemagnitude eruptions of both magma types during LIP formation. In basalt-dominated provinces, large magnitude (>M8) eruptions have much shorter recurrence intervals (10^3-10^4 years) than similar magnitude silicic eruptions (~10^5 years). The huge volumes of magma erupted rapidly in LIPs raises several unresolved issues in terms of locus of magma generation and storage (if any) in the crust prior to eruption, the paths and rates of ascent from magma reservoirs to the surface, and relative aerosol contributions to the stratosphere from the flood basaltic and rhyolitic eruptions.

Prediction of multilocus identity-by-descent

Previous studies have enabled exact prediction of probabilities of identity-by-descent (IBD) in randommating populations for a few loci (up to four or so), with extension to more using approximate regression methods. Here we present a precise predictor of multiple-locus IBD using simple formulas based on exact results for two loci. In particular, the probability of non-IBD X ABC at each of ordered loci A, B, and C can be well approximated by XABC = XABXBC/XB and generalizes to X123. . .k = X12X23. . .Xk-1,k/ Xk-2, where X is the probability of non-IBD at each locus. Predictions from this chain rule are very precise with population bottlenecks and migration, but are rather poorer in the presence of mutation. From these coefficients, the probabilities of multilocus IBD and non-IBD can also be computed for genomic regions as functions of population size, time, and map distances. An approximate but simple recurrence formula is also developed, which generally is less accurate than the chain rule but is more robust with mutation. Used together with the chain rule it leads to explicit equations for non-IBD in a region. The results can be applied to detection of quantitative trait loci (QTL) by computing the probability of IBD at candidate loci in terms of identity-by-state at neighboring markers.

The deep trauma of secondary victimisation : parents of sex offenders

The publication of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) introduced the notion that a life-threatening illness can be a stressor and catalyst for Posttraumatic Stress Disorder (PTSD). Since then a solid body of research has been established investigating the post-diagnosis experience of cancer. These studies have identified a number of short and long-term life changes resulting from a diagnosis of cancer and associated treatments. In this chapter, we discuss the psychosocial response to the cancer experience and the potential for cancer-related distress. Cancer can represent a life-threatening diagnosis that may be associated with aggressive treatments and result in physical and psychological changes. The potential for future trauma through the lasting effects of the disease and treatment, and the possibility of recurrence, can be a source of continued psychological distress. In addition to the documented adverse repercussions of cancer, we also outline the recent shift that has occurred in the psycho-oncology literature regarding positive life change or posttraumatic growth that is commonly reported after a diagnosis of cancer. Adopting a salutogenic framework acknowledges that the cancer experience is a dynamic psychosocial process with both negative and positive repercussions. Next, we describe the situational and individual factors that are associated with posttraumatic growth and the types of positive life change that are prevalent in this context. Finally, we discuss the implications of this research in a therapeutic context and the directions of future posttraumatic growth research with cancer survivors. This chapter will present both quantitative and qualitative research that indicates the potential for personal growth from adversity rather than just mere survival and return to pre-diagnosis functioning. It is important to emphasise however, that the presence of growth and prevalence of resilience does not negate the extremely distressing nature of a cancer diagnosis for the patient and their families and the suffering that can accompany treatment regimes. Indeed, it will be explained that for growth to occur, the experience must be one that quite literally shatters previously held schemas in order to act as a catalyst for change.

Depression among Holocaust survivors : a meta-analytic review

The publication of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) introduced the notion that a life-threatening illness can be a stressor and catalyst for Posttraumatic Stress Disorder (PTSD). Since then a solid body of research has been established investigating the post-diagnosis experience of cancer. These studies have identified a number of short and long-term life changes resulting from a diagnosis of cancer and associated treatments. In this chapter, we discuss the psychosocial response to the cancer experience and the potential for cancer-related distress. Cancer can represent a life-threatening diagnosis that may be associated with aggressive treatments and result in physical and psychological changes. The potential for future trauma through the lasting effects of the disease and treatment, and the possibility of recurrence, can be a source of continued psychological distress. In addition to the documented adverse repercussions of cancer, we also outline the recent shift that has occurred in the psycho-oncology literature regarding positive life change or posttraumatic growth that is commonly reported after a diagnosis of cancer. Adopting a salutogenic framework acknowledges that the cancer experience is a dynamic psychosocial process with both negative and positive repercussions. Next, we describe the situational and individual factors that are associated with posttraumatic growth and the types of positive life change that are prevalent in this context. Finally, we discuss the implications of this research in a therapeutic context and the directions of future posttraumatic growth research with cancer survivors. This chapter will present both quantitative and qualitative research that indicates the potential for personal growth from adversity rather than just mere survival and return to pre-diagnosis functioning. It is important to emphasise however, that the presence of growth and prevalence of resilience does not negate the extremely distressing nature of a cancer diagnosis for the patient and their families and the suffering that can accompany treatment regimes. Indeed, it will be explained that for growth to occur, the experience must be one that quite literally shatters previously held schemas in order to act as a catalyst for change.

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.