Kimberly Rhea Fernandes - Academia.edu (original) (raw)

Papers by Kimberly Rhea Fernandes

World journal of surgery, Jan 21, 2015

Utilization of breast reconstruction (BR) is low in many jurisdictions. We studied the geographic... more Utilization of breast reconstruction (BR) is low in many jurisdictions. We studied the geographical and surgical workforce factors that contribute to access and use of BR using a small area analysis approach with a geographical unit of analysis. We linked administrative data from Ontario Canada to calculate the age-standardized rates for immediate BR (IBR) (same time as mastectomy) between 2002 and 2011, and delayed BR (DBR) (within 3 years of mastectomy) for each county. The influence of plastic surgeon access on variation in county rates of BR was examined using Poisson random effects models. 12,663 women underwent mastectomy in Ontario; 2,948 had BR within 3 years (23.3 %). Over 50 % of the counties had no access to any plastic surgeon. County IBR rates ranged from 0 to 21.5 %; plastic surgeon access explained 46 % of geographic variation (p < 0.0001). IBR rates in counties with very low, low, and moderate access to plastic surgeons were significantly less than counties with h...

European Urology Supplements, 2011

save one men from PCa metastases was 23. Conclusions: A relative reduction in PCa metastases of 3... more save one men from PCa metastases was 23. Conclusions: A relative reduction in PCa metastases of 30% was observed in the intervention population relative to the control population of the ERSPC section Rotterdam. Longer follow up is likely to demonstrate an increasing benefit of PSA screening terms of distant metastases.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 10, 2014

To describe the population-based rates of immediate breast reconstruction (IBR) for all women und... more To describe the population-based rates of immediate breast reconstruction (IBR) for all women undergoing mastectomy for treatment or prophylaxis of breast cancer in the past decade, and to evaluate geographic, institutional, and patient factors that influence use in the publically funded Canadian health care system. This population-based retrospective cohort study used administrative data that included 28,176 women who underwent mastectomy (25,141 mastectomy alone and 3,035 IBR) between April 1, 2002, and March 31, 2012, in Ontario, Canada. We evaluated factors associated with IBR by using a multivariable logistic regression model with the generalized estimating equation approach. The population-based, age-adjusted IBR rate increased from 5.1 procedures to 8.7 in 100,000 adult women (43.7%; P < .001), and the increase was greatest for prophylactic mastectomy or therapeutic mastectomy for in situ breast cancer (78.6%; P < .001). Women who lived in neighborhoods with higher medi...

Journal of Neuroinflammation, 2014

Background: Glaucoma is an optic neuropathy that is characterized by the loss of retinal ganglion... more Background: Glaucoma is an optic neuropathy that is characterized by the loss of retinal ganglion cells (RGCs) initiated by damage to axons in the optic nerve. The degeneration and death of RGCs has been thought to occur in two waves. The first is axogenic, caused by direct insult to the axon. The second is somatic, and is thought to be caused by the production of inflammatory cytokines from the activated retinal innate immune cells. One of the cytokines consistently linked to glaucoma and RGC damage has been TNFα. Despite strong evidence implicating this protein in neurodegeneration, a direct injection of TNFα does not mimic the rapid loss of RGCs observed after acute optic nerve trauma or exposure to excitotoxins. This suggests that our understanding of TNFα signaling is incomplete. Methods: RGC death was induced by optic nerve crush in mice. The role of TNFα in this process was examined by quantitative PCR of Tnfα gene expression, and quantification of cell loss in Tnfα −/− mice or in wild-type animals receiving an intraocular injection of exongenous TNFα either before or after crush. Signaling pathways downstream of TNFα were examined by immunolabeling for JUN protein accumulation or activation of EGFP expression in NFκB reporter mice. Results: Optic nerve crush caused a modest increase in Tnfα gene expression, with kinetics similar to the activation of both macroglia and microglia. A pre-injection of TNFα attenuated ganglion cell loss after crush, while ganglion cell loss was more severe in Tnfα −/− mice. Conversely, over the long term, a single exposure to TNFα induced extrinsic apoptosis in RGCs. Müller cells responded to exogenous TNFα by accumulating JUN and activating NFκB. Conclusion: Early after optic nerve crush, TNFα appears to have a protective role for RGCs, which may be mediated through Müller cells.

Neurobiology of Disease, 2014

Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N-terminal kinase (J... more Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N-terminal kinase (JNK) signaling, a major prodeath pathway in injured RGCs. Of the multiple kinases that can activate JNK, dual leucine kinase (Dlk) is known to regulate both apoptosis and Wallerian degeneration triggered by axonal insult. Here we tested the importance of Dlk in regulating somal and axonal degeneration of RGCs following axonal injury. Removal of DLK from the developing optic cup did not grossly affect developmental RGC death or inner plexiform layer organization. In the adult, Dlk deficiency significantly delayed axonal-injury induced RGC death. The activation of JUN was also attenuated in Dlk deficient retinas. Dlk deficiency attenuated the activation of the somal pool of JNK but did not prevent activation of the axonal pool of JNK after axonal injury, indicating that JNK activation in different cellular compartments of an RGC following axonal injury is regulated by distinct upstream kinases. In contrast to its robust influence on somal degeneration, Dlk deficiency did not alter RGC axonal degeneration after axonal injury as assessed using physiological readouts of optic nerve function.

Journal of Cancer, 2013

Background: The association between age and outcomes in men with castrate resistant prostate canc... more Background: The association between age and outcomes in men with castrate resistant prostate cancer (CRPC) is not well understood. Objective: We aimed to evaluate CRPC patients to determine if their age at initial diagnosis impacted their cancer specific outcomes. Design, Setting, and Participants: A retrospective chart review was conducted on 333 consecutive CRPC patients treated at the Princess Margaret Hospital (PMH) between 1995 and 2005. Patients were divided into 4 age categories, (A) <55, (B) 55-64, (C) 65-74 (reference), and (D) > 75 years (yrs). Outcome Measurements and Statistical Analysis: Primary endpoints included impact of age at diagnosis on overall survival (OS) and on prostate cancer specific survival. Secondary endpoints were time from diagnosis to development of CRPC, time from CRPC to death, and time from diagnosis to bone metastases. Results and Limitations: The median OS from diagnosis to death was: Group A 5.5 yrs (95% CI 3.0-7.5); Group B 6.7 yrs (95% CI 5.9-8.4); Group C 7.8 yrs (95% CI 6.6-9.3); and Group D 4.3 years (95% CI 2.9-5.0). The hazard ratio (HR) for death in Group D was 2.58 (95% CI 1.58-4.21, p=0.0002); and in Group A was 1.49 (95% CI 0.90-2.46, p=0.13). The duration of hormone sensitivity in Group D was less and predictive of OS, as was Gleason Score >8 and Stage 4 disease at diagnosis. Conclusions: Age at initial diagnosis appears to impact on outcome of patients who subsequently develop CRPC with a bimodal distribution of risk, with the shortest survivals in the >75 and <55 groups.

Scientific Reports, 2012

Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-... more Axonal insult induces retinal ganglion cell (RGC) death through a BAX-dependent process. The pro-apoptotic Bcl-2 family member BIM is known to induce BAX activation. BIM expression increased in RGCs after axonal injury and its induction was dependent on JUN. Partial and complete Bim deficiency delayed RGC death after mechanical optic nerve injury. However, in a mouse model of glaucoma, DBA/2J mice, Bim deficiency did not prevent RGC death in eyes with severe optic nerve degeneration. In a subset of DBA/2J mice, Bim deficiency altered disease progression resulting in less severe nerve damage. Bim deficient mice exhibited altered optic nerve head morphology and significantly lessened intraocular pressure elevation. Thus, a decrease in axonal degeneration in Bim deficient DBA/2J mice may not be caused by a direct role of Bim in RGCs. These data suggest that BIM has multiple roles in glaucoma pathophysiology, potentially affecting susceptibility to glaucoma through several mechanisms. B AX is a critical mediator of neuronal cell death. In the retina, Bax deficiency protects against developmental apoptosis of many retinal cells, including, retinal ganglion cells (RGCs) 1-5. BAX is also an important mediator of RGC loss after axonal insult. BAX is up-regulated in response to optic nerve injury 6 and its suppression rescues RGC somas from death after mechanical optic nerve injury 2,3,7. Bax was also shown to be required for RGC death in an animal model of glaucoma 3 , a common neurodegeneration where elevated intraocular pressure (IOP) ultimately leads to an RGC axonal insult 8-11. Importantly, other apoptotic or non-apoptotic pathways do not circumvent the long-term protection provided by Bax deficiency 3,7. Thus, BAX is major mediator of RGC death in disease. The funneling of cell death pathway(s) to a central point in glaucoma-BAX activation-provides a powerful starting point for unraveling the complex process that determines RGC survival in glaucoma. BAX is a member of the Bcl-2 family of proteins 12. Direct interactions between different family members (both pro-survival and pro-death family members) determine the likelihood of BAX activation in a cell. BH3-only proteins are pro-death Bcl-2 family members that trigger cell death through BAX activation. After injury, activation of different BH3-only proteins occurs in an insult and context-specific manner 12. For example, BBC3 is required for BAX activation in developing RGCs, but does not play a primary role in regulating RGC death after axonal injury 1. In fact, it is unknown which BH3-only proteins, if any, are required for RGC death after axonal injury and in glaucoma. The BH3-only protein BIM is a good candidate for activating BAX in axonallyinjured RGCs. After optic nerve injury, Bim transcription increases in the retina and BIM is detected in the RGC layer 6,13,14. In addition, an ex vivo study demonstrates a pro-apoptotic function for BIM early after axonal insult 13. However, it is unknown if BIM is required for RGC death after axonal injury in vivo or if its role varies based on the type of axonal insult. The importance of BIM was tested in vivo after optic nerve crush and in glaucoma and, unlike BAX, BIM is not required for RGC death in these models. Surprisingly, BIM was found to have multiple functions, both intrinsic and extrinsic to RGCs, relevant to glaucoma pathophysiology. Results BIM plays several roles in retinal morphogenesis. BIM is expressed in the developing retina 15 , suggesting that it may regulate normal retinal developmental cell death. As previously reported 1,16,17 , Bim deficiency does not grossly affect retinal neuronal patterning (Fig. 1A). BIM is known to be critical for retinal vasculature remodeling and deficiency in Bim does increase the amount of retinal vasculature (17 and data not shown). In

Urology, 2014

To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk ... more To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers. The primary outcome was any PC on biopsy, and the secondary outcome was clinically significant PC (CSPC; Gleason sum ≥7). Multivariate logistic regression analyses were performed to adjust for a priori defined clinical confounders. Of 839 patients, 408 (48.6%) were diagnosed with PC and 201 (24.0%) had CSPC. A higher proportion of ASA users (63.5%) and other NSAID users (61.2%) had PC compared with nonusers (41.9%; P <.001). CSPC was more common among ASA users (34.9%; P…

Globalization and Health, 2014

Background: We describe trends in participation by investigators from low-and middle-income count... more Background: We describe trends in participation by investigators from low-and middle-income countries (LMCs) in publications describing oncology randomized control trials (RCTs) over a decade. Methods: We used Medline to identify RCTs published in English from 1998 to 2008 evaluating treatment in lung, breast, colorectal, stomach and liver cancers. Data on author affiliations, authorship roles, trial characteristics, funding and interventions were extracted from each article. Countries were stratified as low-, middle-or high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression was used to identify factors associated with authorship by investigators from LMCs. Results: 454 publications were identified. Proportion of articles with at least one LMC author increased over time from 20% in 1998 to 29% in 2008 (p = 0.01), but almost all LMC authors were from middle-income countries. Proportion of articles with at least one LMC author was higher among articles that explicitly reported recruitment in at least one LMC vs those that did not (76% vs 13%). Among 87 articles (19%) that involved authors from LMCs, 17% had LMC authors as first or corresponding authors, and 67% evaluated interventions requiring enhanced or maximal resources. Factors associated with LMC authorship included industry funding (OR = 3.54, p = 0.0001), placebo comparator arm (OR = 2.57, p = 0.02) and palliative intent treatment (OR = 4.00, p = 0.0003). Conclusion: An increasing number of publications describing oncology RCTs involve authors from LMC countries but primarily in non-leadership roles in industry-funded trials.

Social Science & Medicine, 2009

Migration among persons with HIV/AIDS is common; however, it is not clear how migration relates t... more Migration among persons with HIV/AIDS is common; however, it is not clear how migration relates to antiretroviral adherence, a key determinant of treatment efficacy. Therefore, our objective was to determine the scale of regional migration and its association with adherence patterns over time among HIV-infected individuals in British Columbia (BC), Canada. Participants initiated HAART in August 1996-November 2004, and were followed until November 2005. Adherence was defined as the number of days worth of antiretrovirals dispensed divided by the number of days of follow-up (expressed as a percentage), and considered a binary time-dependent outcome: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;non-adherence&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (less than 95%) versus &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;adherence&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; (95% or more). Migration was calculated as the cumulative number of times a patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s residential address changed during the course of treatment, and treated as a time-dependent variable. Non-linear mixed-effects models were used to estimate the association between migration and adherence over time. All analyses were adjusted for relevant fixed and time-dependent variables. A total of 2421 participants were followed during the study period. Descriptive analysis demonstrated high stability in adherence over time, with more than 55% of patients moving at least once during the course of their treatment. We observed that those individuals migrating at least 3 times were 1.79 times more likely to be in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;non-adherence&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; group than individuals who did not migrate. Our results demonstrate that migration in BC is not homogeneous across subpopulations. These results suggest that proactive strategies are needed to ensure that antiretroviral therapy remains available on a continued basis to highly migrant populations.

PLoS ONE, 2014

Purpose: To investigate the role of Pou4f1 and Pou4f2 in the survival of adult retinal ganglion c... more Purpose: To investigate the role of Pou4f1 and Pou4f2 in the survival of adult retinal ganglion cells (RGCs). Methods: Conditional alleles of Pou4f1 and Pou4f2 were generated (Pou4f1 loxP and Pou4f2 loxP respectively) for the removal of Pou4f1 and Pou4f2 in adult retinas. A tamoxifen-inducible Cre was used to delete Pou4f1 and Pou4f2 in adult mice and retinal sections and flat mounts were subjected to immunohistochemistry to confirm the deletion of both alleles and to quantify the changes in the number of RGCs and other retinal neurons. To determine the effect of loss of Pou4f1 and Pou4f2 on RGC survival after axonal injury, controlled optic nerve crush (CONC) was performed and RGC death was assessed. Results: Pou4f1 and Pou4f2 were ablated two weeks after tamoxifen treatment. Retinal interneurons and Mü ller glial cells are not affected by the ablation of Pou4f1 or Pou4f2 or both. Although the deletion of both Pou4f1 and Pou4f2 slightly delays the death of RGCs at 3 days post-CONC in adult mice, it does not affect the cell death progress afterwards. Moreoever, deletion of Pou4f1 or Pou4f2 or both has no impact on the long-term viability of RGCs at up to 6 months post-tamoxifen treatment. Conclusion: Pou4f1 and Pou4f2 are involved in the acute response to damage to RGCs but are dispensable for the long-term survival of adult RGC in mice.

Neurobiology of Disease, 2012

Glaucoma is a neurodegenerative disease characterized by the apoptotic death of retinal ganglion ... more Glaucoma is a neurodegenerative disease characterized by the apoptotic death of retinal ganglion cells (RGCs). The primary insult to RGCs in glaucoma is thought to occur to their axons as they exit the eye in the optic nerve head. However, pathological signaling pathways that exert central roles in triggering RGC death following axonal injury remain unidentified. It is likely that the first changes to occur following axonal injury are signal relay events that transduce the injury signal from the axon to the cell body. Here we focus on the c-Jun N-terminal kinase (JNK1-3) family, a signaling pathway implicated in axonal injury signaling and neurodegenerative apoptosis, and likely to function as a central node in axonal injury-induced RGC death. We show that JNK

Molecular and Cellular Neuroscience, 2012

The Bcl-2 family is responsible for regulating cell death pathways in neurons during development,... more The Bcl-2 family is responsible for regulating cell death pathways in neurons during development, after injury and in disease. The activation of the pro-death family member BAX is often the final step before cell death in neurons. Pro-survival family members such as BCL-X (BCL2L1) act to inhibit BAX activation. Overexpression studies have suggested that BCL-X could play an important physiological role in mediating neuronal viability. Loss-of-function studies performed in vivo have implicated BCL-X as a mediator of neuronal survival during the early stages of neurodevelopment. To assess whether BCL-X is needed to promote the survival of neurons in the central nervous system throughout life, Bcl-x was conditionally removed from the optic cup or throughout the adult mouse. During development BCL-X was required for the survival of differentiating retinal ganglion cells (RGCs) leading up to their normal window of developmental death. Despite its expression in adult RGCs, BCL-X was not required for maintaining RGC viability in adult retinas. However, the loss of BCL-X in adult RGCs did significantly increase the rate of death of RGCs after axonal injury. Thus, in developing and injured RGCs there appears to be an active cell survival program preventing neuronal death.

Journal of Urology, 2011

We examined the growth of tissue proven renal oncocytoma on serial imaging to improve our underst... more We examined the growth of tissue proven renal oncocytoma on serial imaging to improve our understanding of its natural history. Materials and Methods: We reviewed the charts of 69 patients with oncocytoma diagnosed by biopsy or surgery between 2004 and 2010. A total of 29 cases were managed by active surveillance for at least 12 months and had 3 or more imaging events. Tumor size was documented and the average tumor growth rate was calculated using a random coefficient model. Interaction terms were used to investigate correlations between variables of interest, including age at diagnosis, gender, symptom status, laterality, initial tumor size, surveillance duration and number of imaging events. Results: At a mean surveillance duration of 40 months 80% of oncocytomas increased in size. Based on the random coefficient model the estimated average growth rate was 0.16 mm monthly (95% CI 0.097-0.228, p Ͻ0.0001). We identified no variables that significantly correlated with growth. Conclusions: Despite its low metastatic potential renal oncocytoma appears to progress locally with a growth rate similar to that of RCC. Thus, absent tumor growth on serial imaging is not a robust prognostic factor for benign histology. Biopsy remains the mainstay of diagnosis. At centers where it can be performed safely and accurately, active surveillance of tissue proven oncocytoma appears to be safe in the short term. Alternative management includes partial nephrectomy and minimally invasive approaches. To our knowledge this is the largest study of oncocytoma natural history.

Journal of Urology, 2010

INTRODUCTION AND OBJECTIVES: Nephroblastomas in postpubertal patients (defined as 13 years of age... more INTRODUCTION AND OBJECTIVES: Nephroblastomas in postpubertal patients (defined as 13 years of age or older) are rare and usually the subject of individual case reports or small groups of patients. The purpose of this study is to report on the experience of the Armed Forces Institute of Pathology. METHODS: The Kidney Tumor Registry of the AFIP contains 97 patients diagnosed as nephroblastoma in postpubertal patients beginning in 1967. The clinical charts and slides were reviewed and the tumors were classified using the same categories as the pediatric age group, and the same definition for unfavorable histology. RESULTS: Triphasic tumors were identified in 15 patients (8 males and 7 females) from the 2nd to 8th decades, and 10 died of disease. Blastemal tumors were found in 37 patients (23 males and 14 females), mostly in the 3rd decade. Ten died of disease and 4 were living with disease. Biphasic epithelial /blastemal tumors were seen in 33 patients (10 male and 17 females, with sex in the reminder unknown), mostly in the 2nd and 3rd decades. Only one death was observed in this group, occurring in a patient with unfavorable histology. Nine were living and well. Pure epithelial tumors, 5 with focal maturation, were found in 12 patients (5 males and 7 females), mostly in the 2nd and 3rd decades, and only one died of disease. Seventy-five percent of triphasic tumors were stage II or greater, 55% of blastemal tumors were stage II or greater, and 64% of biphasic tumors were stage II or greater. In contrast, eight of twelve pure epithelial tumors (including all with maturation) were stage I. CONCLUSIONS: In postpubertal patients, triphasic and blastemal nephroblastomas behaved aggressively, whereas biphasic did so only if unfavorable histology was present. Epithelial nephroblastomas had a good prognosis, particularly if there was evidence of maturation.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2009

Background-Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes ... more Background-Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes but there is little data on this issue. We assessed associations between food insecurity and mortality in HIV-infected antiretroviral therapy (ART)-treated individuals in Vancouver, British Columbia (BC), and whether body max index (BMI) modified associations. Methods-Individuals were recruited from the BC HIV/AIDS drug treatment program in 1998 and 1999, and were followed until June 2007 for outcomes. Food insecurity was measured with the Radimer/Cornell questionnaire. Cox proportional hazard models were used to determine associations between food insecurity, BMI and non-accidental deaths when controlling for confounders. Results-Among 1119 participants, 536 (48%) were categorized as food insecure and 160 (14%) were categorized as underweight (BMI <18.5). After a median follow-up time of 8.2 years, 153 individuals (14%) had died from non-accidental deaths. After controlling for adherence, CD4 counts, and socioeconomic variables, people who were food insecure and underweight were nearly two times more likely to die (Adjusted hazard ratio [AHR]=1.94, 95% Confidence interval [CI]=1.10-3.40) compared with people who were not food insecure or underweight. There was also a trend towards increased risk of mortality among people who were food insecure and not underweight (AHR= 1.40, 95% CI=0.91-2.05). In contrast, people who were underweight but food secure were not more likely to die.

Experimental Eye Research, 2013

The AP1 family transcription factor JUN is an important molecule in the neuronal response to inju... more The AP1 family transcription factor JUN is an important molecule in the neuronal response to injury. In retinal ganglion cells (RGCs), JUN is upregulated soon after axonal injury and disrupting JUN activity delays RGC death. JUN is known to participate in the control of many different injury response pathways in neurons, including pathways controlling cell death and axonal regeneration. The role of JUN in regulating genes involved in cell death, ER stress, and regeneration was tested to determine the overall importance of JUN in regulating RGC response to axonal injury. Genes from each of these pathways were transcriptionally controlled following axonal injury and Jun deficiency altered the expression of many of these genes. The differentially expressed genes included, Atf3, Ddit3, Ecel1, Gadd45α, Gal, Hrk, Pten, Socs3, and Sprr1a. Two of these genes, Hrk and Atf3, were tested for importance in RGC death using null alleles of each gene. Disruption of the prodeath Bcl2 family member Hrk did not affect the rate or amount of RGC death after axonal trauma. Deficiency in the ATF/CREB family transcription factor Atf3 did lessen the amount of RGC death after injury, though it did not provide long term protection to RGCs. Since JUN's dimerization partner determines its transcriptional targets, the expression of several candidate AP1 family members were examined. Multiple AP1 family members were induced by axonal injury and had a different expression profile in Jun deficient retinas compared to wildtype retinas (Fosl1, Fosl2 and Jund). Overall, JUN appears to play a multifaceted role in regulating RGC response to axonal injury.

BJU International, 2011

PCa was detected in 46% and high-grade (HG) PCa (Gleason ≥ 4) in 23% of subjects with a median PS... more PCa was detected in 46% and high-grade (HG) PCa (Gleason ≥ 4) in 23% of subjects with a median PSA level of 6.02 ng/mL. • Multivariable analysis identified transrectal ultrasonography nodule, prostate volume and PSA as the most important predictors of PCa and HG PCa. • ROC curve analysis showed that the ERSPC-RC (AUC = 0.71) outperformed the PCPT-RC (AUC = 0.63) and PSA (AUC = 0.55), for PCa prediction, P < 0.001. • The PCPT-RC was better calibrated in the higher prediction range (40-100%) than the ERSPC-RC, whereas the ERSPC-RC had better calibration and avoided more biopsies in the lower risk range (0-30%). • Discrimination of the ERSPC-RC continued to be superior to the PCPT-RC when the cohort was stratified by different clinical variables. CONCLUSIONS • The ERSPC-RC had better discrimination for predicting PCa compared to the PCPT-RC in this Canadian cohort. • Calibration would need to be improved to allow routine use of the ERSPC-RC in Canadian practice.