This finding is encouraging in that rehabilitation could possibly ameliorate deficits. Gaze direction is another modulator of amygdala response. In healthy people, directed fear and averted anger expressions produced greater amygdala response than averted fear and directed anger.

This effect was interpreted to suggest that the amygdala is especially sensitive to threat-related ambiguity. Since poor eye contact is a major feature of impaired social interactions in schizophrenia, gaze direction and evaluation of the patient’s ability to use information in the eyes region seems the most appropriate target for the Inhibitors,research,lifescience,medical next phase of investigation. Although scan-path Inhibitors,research,lifescience,medical studies reported a restricted range of visual scanning in schizophrenia for happy, sad, and neutral

faces, these studies have not indicated a difference between the eyes and the mouth region. However, fear and anger stimuli have not been used. Because amygdala damage leads to avoidance of the eyes region in fearful faces, and the eyes region is important for distinguishing anger from fear, the difficulty of patients in identifying fear could be related to impairment in recognizing changes in the eyes region, thereby diminishing amygdala response to Inhibitors,research,lifescience,medical fear in the eyes relative to the mouth region. As with other bottom-up activation abnormalities, we expect the severity of these abnormalities to be associated with poorer eye contact and affective Inhibitors,research,lifescience,medical flattening. Pharmacology The literature on the possible effects of antipsychotic agents on BOLD signal change is relatively limited.21,22 Few studies have examined neuroleptic-naïve patients, and fewer still applied a pre -post paradigm. Furthermore, small samples and methodologically limited designs have precluded systematic examination of the possible effects of therapeutics. Examples of studies include a working memory evaluation with an n-back paradigm after patients Inhibitors,research,lifescience,medical switched from first-generation antipsychotics

to a second generation agent. Increased dosolateral prefrontal cortex and parietal cortex activity were reported in the patients with the new treatment.23 Similarly, normalization of brain activity was reported in patients treated with long-acting risperidone compared with conventional depot P450 inhibitor medication while performing an n-back task.24 Normalization of prepulse inhibition was noted in patients treated with olanzapine all and risperidone compared with those on first-generation antipsychotics.25 Studies that examined motor control in relation to medications have also noted improved brain activity in patients treated with second-generation agents compared with first generation antipsychotics. Given the limited number and scope of the available literature, there is no conclusive evidence, and double-blind studies are needed.

Until more clinical labs are capable of measuring melatonin in saliva, clinicians must proceed without this test and the recommendations of Table I remain state-of-the-art.

Since most patients with SAD are of the phasedelayed type, morning light should usually be tried first. Failure to respond is apparent within the first week of treatment, after which bright light should be switched to the evening. If morning bright Inhibitors,research,lifescience,medical light causes too much of a phase advance, patients will start to complain of early-morning awakening. Selected abbreviations and acronyms PSH phase shift hypothesis DLMO dim light melatonin onset SAD seasonal affective disorder PRC phase response curve PAD Inhibitors,research,lifescience,medical phase angle difference Notes We thank the research subjects, the nursing staff of the Oregon Health & Science University (OHSU) Clinical and Translational Research Center, Diana Arntz and Kathryn Woods. This work was supported by Public Health Service

Grants R01MH55703, R01MH56874, R01AG21826, and R01HD42125 (to AJ.L) and 5 M01RR000334 (to the Clinical and Translational Research Center of OHSU). AJ.L. was supported by the National Alliance for Research on Schizophrenia and Depression 2000 Distinguished Investigator Inhibitors,research,lifescience,medical Award. J.S.E. was supported by Public Health Service Grant K23 RR017636-01. Contributor Information Alfred J. Lewy, Oregon Health & Science University, Department of Psychiatry, Sleep and Mood Disorders Laboratory Portland, Oregon, Inhibitors,research,lifescience,medical USA. Jennifer N. Rough, Oregon Health & Science University, Department of Psychiatry, Sleep and Mood Disorders Laboratory Portland, Oregon, USA. Jeannine B. Songer, Oregon Health & Science University, Department of Psychiatry, Sleep and Mood Disorders Laboratory Portland, Oregon, USA. Neelam Mishra, Oregon Health & Science University, Department of Psychiatry, Sleep and Mood Disorders Laboratory Portland, Oregon, USA. Krista Yuhas, Oregon Health & Science University, Department of Psychiatry, Sleep and Mood Disorders Laboratory Inhibitors,research,lifescience,medical Portland, Oregon, USA. Jonathan S. Emens, Oregon Health & Science University, Department of Psychiatry,

Sleep and Mood Disorders Laboratory Portland, Oregon, USA.
The view that living organisms are three-dimenslonal beings, with height, length and depth, might be correct when Selleck VX 809 applied to gross anatomy, but represents a simplified and misleading description of most aspects of physiology and biochemistry. Biology operates in the fourth dimension, ie, time, and the number and extent aminophylline of time-related and oscillating bodily functions Is huge: most physiological functions are coded or structured In time. This conclusion comes from clinical studies of a descriptive nature, as well as from in-vitro studies on Isolated cells or cell groups from multicellular organisms, and on unicellular organisms.1 For example, In endocrinology, the extent of a cell secretory response depends on the interspike and Interburst Intervals from afferent axons.

The KM OS analysis for each dose level is shown in Figure 1. Figure 1 Kaplan Meier overall survival curves by dose level. In the UV survival

analysis, several different adjuvant treatment parameters were associated with Dasatinib purchase higher risk of death including RT dose below the median, RT dose <30 Gy, and RT dose ≥30 to <40 Gy, and shorter radiation duration. Factors significantly associated with lower risk of death included, smaller tumor size, lower grade, and younger age. The results of the complete UV can be found in Table 2. Table 2 Univariate survival analysis The UV associated between categorized radiation dose and all other covariates Inhibitors,research,lifescience,medical are summarized in Table 3. Factors found to be significantly correlated with the different dose level categories of RT included facility type, tumor size, and Inhibitors,research,lifescience,medical grade. It can be seen that the RT dose was independent of stage. Table

3 Variable association with RT dose levels In the MV Inhibitors,research,lifescience,medical survival analysis, RT dose <30 Gy [HR, 2.38 (95% CI, 1.85-3.07); P≤0.001] and RT dose ≥30 Gy and <40 Gy [HR, 1.41 (95% CI, 1.04-1.91); P=0.026] vs. RT dose ≥55 Gy; were significantly associated with worse OS. In addition to radiation dose, age was also found to be significant on MV analysis. The complete MV survival analysis can be seen in Table 4. As the results of the MV survival analysis were not significantly different with and without the propensity score weighting, we present the unweighted results only. Table 4 Multivariate survival analysis The duration of time over which each Inhibitors,research,lifescience,medical of the respective RT doses was delivered is summarized in Table 5. It can be seen that the vast majority of patients for which

the RT duration was known received conventionally fractionated RT. Table 5 Duration of radiation therapy administration Discussion The purpose of this analysis of the NCDB Inhibitors,research,lifescience,medical was to examine the effect of RT dose escalation in a large cohort of patients with unresectable PAC. This series presents a heterogeneous group of patients, ALOX15 treated in a variety of facility types, with a wide range of RT doses. There was no measureable benefit or detriment to OS in patients treated with conventionally delivered, escalating RT doses greater than 40 Gy. There exists a historical precedent for RT dose escalation in unresectable PAC. An early prospective study examining RT dose escalation was the Gastrointestinal Tumor Study Group’s (GITSG) locally advanced dose escalation trial (5). Published in 1981, this prospective trial randomized 194 patients to 60 Gy of RT alone or concurrent chemo-RT with dose escalated RT consisting of 40 vs. 60 Gy.

The current guidelines of the World Federation of Societies

of Biological TGF-beta family Psychiatry (WFSBP) for the pharmacological treatment of OCD24 grant the highest category of evidence (“A”, ie, full evidence from several RCTs) for the SSRIs escitalopram, fluvoxamine, fluoxetine, paroxetine, and sertraline, as well as for the TCA clomipramine, but not for any other drug. Because Inhibitors,research,lifescience,medical clomipramine is less well tolerated than the SSRIs, it was given a recommendation grade of 2 (moderate risk benefit ratio), while the SSRIs received the highest recommendation grade 1 (good risk:benefit ratio). As for citalopram, only one positive double-blind, placebo-controlled study was published, and only a recommendation grade Inhibitors,research,lifescience,medical of 3 (limited evidence from controlled studies) was given. This WFSBP guideline mentions that usually lower response rates are achieved in OCD in comparison with other anxiety disorders, and that sometimes only partial remission is achieved. As a rule, somewhat higher doses are used for these drugs in OCD than for other anxiety disorders, higher doses being associated with greater efficacy in some, but not all, evaluations. Inhibitors,research,lifescience,medical In several longterm and relapse-prevention studies, SRIs were shown to be superior

to placebo, pointing to the requirement of long-term treatment of OCD. According to a systematic review on all long-term, placebo-controlled trials with SSRIs in OCD,25 the likelihood of relapse during 24 to 52 weeks of treatment was significantly lower on an SSRI than with placebo. Inhibitors,research,lifescience,medical Thus, successful treatment with SSRIs should be maintained at the maximal effective dose for at least 12 months. An extensive display of the many acute Inhibitors,research,lifescience,medical treatment studies on SSRIs versus placebo, different doses of SSRIs, SSRIs versus other SSRIs, clomipramine versus placebo, SSRIs versus clomipramine, SSRIs versus placebo, or clomipramine for continuation

treatment and SSRIs vs placebo or clomipramine for relapse-prevention treatment can also be found in the guidelines on core interventions in the treatment no of OCD of the National Institute for Health and Clinical Excellence (NICE) of the British Psychological Society and the Royal College of Psychiatrists.21 According to these guidelines, the initial pharmacological treatment in adults with OCD should be one of the following SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram. Of note, studies on the efficacy of escitalopram in OCD were published only later.26 A current Cochrane review of placebo-controlled SSRI trials in OCD, comprising 17 studies with 3097 participants, also showed efficacy for all SSRIs included (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline).27 The authors detected no statistical differences in short-term therapeutic action among the individual SSRIs.

We used CARS microscopy to image in situ solid-state

Libraries conversions of samples during dissolution in real time. The combination of CARS microscopy with flow through UV absorbance spectroscopy allowed us to correlate the visualized polymorphic conversion with changes in dissolution rates. Additionally the inhibition of TPm crystal growth due to the presence KRX-0401 order of MC was correlated with changes in dissolution rate for TPa compacts. Hyperspectral CARS microscopy provided a rapid visual technique to confirm the polymorphic conversion that occurred during dissolution. The combination of the rapid analysis and chemical selectivity of CARS and hyperspectral CARS with UV absorption spectroscopy has the potential buy TSA HDAC to allow improved characterization of solid dosage forms undergoing dissolution. CARS with UV absorption spectroscopy allows further in depth analysis on dosage forms exhibiting unexpected dissolution profiles, including failed dissolution tests. Improved characterization of solid dosage forms undergoing dissolution will help in the development of formulations where dissolution profiles are especially important. Formulations such as those containing a poorly soluble APIs and controlled release formulations,

where bioavailability is dissolution- or release-rate limited will benefit from improved characterization. AF is supported by the Dutch Technology Foundation STW, which is the applied science division of NWO, and the Technology Program of the Ministry of Economic Affairs (STW Bumetanide OTP 11114). EG is supported by a NWO VICI grant to Professor Jennifer Herek. BASF is acknowledged for the generous donation of theophylline anhydrate and monohydrate. Colorcon is acknowledged for the generous

donation of methyl cellulose. We thank Coherent Inc. for the Paladin laser and APE Berlin GmbH for the Levante Emerald OPO. “
“αVβ3 Integrin, a transmembrane glycoprotein receptor highly expressed on the surface of activated endothelial cells during angiogenesis as well as on some types of tumor cells, is one of the key biomarkers for tumor angiogenesis and plays important roles in tumor growth, invasion, metastasis, and angiogenesis [1], [2] and [3]. By using a Regioselectively Addressable Functionalized Template (RAFT) cyclodecapeptide scaffold (Fig. 1), we have previously developed a cRGD (cyclic pentapeptide containing the tripeptide sequence Arg-Gly-Asp) probe encompassing (1) the αVβ3-targeting domain, a cluster of 4 copies of a cyclo(-RGDfK-) monomer and (2) a bifunctional chelator 1,4,8,11-tetraazacyclotetradecane (cyclam) for 64Cu radiolabeling. This compound was referred to as 64Cu-cyclam-RAFT-c(-RGDfK-)4[4], [5] and [6]. 64Cu (t1/2 12.7 h) is a promising radionuclide with multiple decay modes—β+ (17.8%) used for positron emission tomography (PET) [7] and β− (38.

4-8 Parallel declines in IGF-I have also been observed by ourselves and others.4,9,10 A variety of mechanisms could potentially underlie this decline in GH secretion with aging. Current evidence suggests that this is most likely the result of both a decrease in GHS activity and an increase in somatostatin, but not an intrinsic loss of pituitary Inhibitors,research,lifescience,medical capacity to secrete GH. Consequently, stimulation of the somatotrophic axis with GHRH is a potential alternative to replacement with GH itself in normal aging. GHSs such as GHRH may result in a more “physiological”

stimulus to GH secretion than GH per se. GHRH yields a pulsatile GH secretion as opposed the continuously elevated levels seen with GH administration. Further, when a secretogogue is used, the normal negative feedback regulation by

Inhibitors,research,lifescience,medical IGF-I on pituitary GH secretion is preserved, offering the possibility of reduced side AZD6244 effects. The hypothesis that age-related decreases in IGF-I and protein synthesis are due to an age-associated decrement in GH secretion is supported by studies showing that exogenous GH administration restores plasma Inhibitors,research,lifescience,medical IGF-I to youthful levels in aged animals and humans.11-13 Similarly, IGF-I restores protein synthesis and lean body mass (LBM) in animals and humans.11,14,15 Thus, the age changes in the GH-IGF-I axis and LBM appear to be at least partly reversible. Aging, sleep and somatotrophic hormones Nearly 40% of the older (over 55 years) population suffers from and complains of insomnia, fragmented sleep, and poor sleep quality, more than

any other age group.16-19 Older individuals are twice as likely to complain of difficulties falling asleep and remaining asleep, and of having less restful sleep than younger individuals. These complaints of poor sleep are supported by objective findings Inhibitors,research,lifescience,medical in the sleep laboratory, which include: Inhibitors,research,lifescience,medical (i) a decrease in stages 3 and 4 sleep (slow-wave sleep [SWS]), often called “deep” sleep, and the delta electroencephalography (FRG) activity that characterizes it; (ii) an increase in the number of awakenings from sleep and an increase in the total time spent awake; and (iii) a decrease in the rapideye-movement (REM) sleep stage. We20,21 and others have shown that these disturbed sleep patterns are seen even in optimally healthy, noncomplaining, Oxygenase elderly individuals who have been carefully screened for possible medical and psychological factors that might disrupt sleep. The public health burden associated with sleep disturbances in the elderly is considerable. These sleep disturbances have been linked to increased use of sedative hypnotics,22-5 greater use of the health services,22,26-28 and reduced functional ability and quality of life.17,18,29,30 Further, these sleep disturbances are frequently comorbid with physical and mental illness,22,28,31-34 are often a major reason for nursing home placement,35,36 and may predict future declines in physical health and mortality.

The letters of intent are reviewed against mandatory criteria, as well as against their technical merit, public health value and potential regional impact. Eligible manufacturers are invited to submit full click here proposals, which are scored, ranked and weighted by TAG members according to

an evaluation of five elements: the project plan; the staffing and management plan; performance measures; an understanding of the requirements; and the budget justification. The technical evaluation is completed by a programmatic review, e.g. on government support and sustainability, and by the results of site audits on production, Good Manufacturing Practices, and biosafety requirements. Two review processes were completed in 2008 and in 2009, resulting in 11 awards (Table 2). Once initial awards are made and the programme of work is under way, members of the TAG make site visits to assess the progress and gauge the value and use of the WHO grant funds in accomplishing the ultimate goal of assuring the access of developing country populations to a safe, effective and affordable pandemic influenza vaccine. In addition, TAG members review the quarterly reports submitted to WHO by the grantees, and have access to a dedicated, Rucaparib confidential extranet sharepoint system elaborated by WHO. Annual TAG meetings complement

regular teleconferences and often take place at one of the grantee sites, to provide an opportunity for hands-on interaction and coincide with meetings of all the international partners. Of note is the broad spectrum of grant recipients.

Vaccine manufacturers range from large companies producing significant quantities of a broad range of vaccines to small- or medium-sized organizations producing only basic products such as diphtheria–pertussis–tetanus vaccine and are just now beginning to expand into other vaccines. Interestingly, only two of the grant recipients are for-profit companies, while nine are government-sponsored organizations. Almost universally, the WHO Libraries grants are small in relation to the overall investment these companies are making Terminal deoxynucleotidyl transferase in influenza vaccine production. But commonly, the grantees express that the benefit of having WHO involved, both via finance and expertise, has far more value than the monetary support alone. This value comes directly from the relative freedom of using WHO funds as well as indirectly from the endorsement of WHO of the applicant’s overall influenza plans, approaches and efforts. The latter gives other funders, especially their own governments, confidence that the quality of effort is of a high standard. Furthermore, independent, external WHO reviews of the projects help assure companies and governments that their investment is wise, reasonably managed and that the probability of technical success is high. Indeed, these reviews, carried out by WHO and TAG members, prove valuable from many vantages.

In addition, high risk alcohol and drug use is positively correlated with PTSD symptomatology [12]. Several mitigating factors for PTSD in emergency workers and trainees have been identified. For example, social support following a traumatic incident has been found to be protective against PTSD [8,13,14]. In one study, ECW who reported strong peer support also reported lower levels of perceived stress [15]. Similarly, a Dutch study found that lack of social support from supervisors greatly compounded symptoms of burnout in ambulance

personnel [16]. Resilience, the ability to cope with adversity without being harmed by it, can also buffer against the onset of PTSD symptoms, Inhibitors,research,lifescience,medical and resilience-recovery Inhibitors,research,lifescience,medical variables (personality, coping strategies and social support) can aid in trauma adjustment [17,18]. ECW are exposed to living individuals who are seriously injured or dying and, as such, are exposed to human pain and suffering [2]. They have to make quick appraisals and administer aid in an attempt to save lives, often Inhibitors,research,lifescience,medical without support or reassurance [4]. ECW workers are frequently unaware of the specifics of the emergency situation as they are often the first personnel on site and consequently do not have adequate time

or information to mentally prepare themselves. Due to the nature of their work, ECW face an increased risk of developing PTSD symptoms. The purpose of this study was firstly to assess and Inhibitors,research,lifescience,medical determine the frequency, nature and severity of direct trauma

exposure, posttraumatic stress symptoms and other psychopathology amongst paramedic trainees. Secondly, the study aimed to identify risk factors (e.g. trauma exposure) and resilience factors (e.g. social support) that contribute to the presence and severity of posttraumatic symptomatology amongst paramedic trainees. Thirdly, the study aimed to create a risk profile for paramedic trainees who Inhibitors,research,lifescience,medical are at higher occupational risk of developing PTSD. Methods Participants and procedure A hundred and thirty one paramedic trainees participated in the study. Data were collected between 2008 and 2011. Participants were recruited from click here a university in the Western Cape with the aid and permission of their supervisors. All the participants were first year paramedic trainees. During their first year of study, trainees gain practical experience in the field and are exposed to accident scenes and critical incidents. The study was approved by the Health Research Ethics Committee at Stellenbosch University, Cape Town, South Africa (N06/02/037). Informed consent was obtained from participants before assessment commenced. Two researchers (a psychiatry resident and research check details psychologist) conducted the assessments. Participants were assessed with a battery of questionnaires including a demographic questionnaire as well as several measures of psychiatric and psychological status.

Although this was never intended as a part of the process, it should be considered for future research to improve rigour. Participants did receive a report documenting the results of the larger study. Another limitation is that the structure of the LWHP likely influenced the content of the journals, as it included watching the The Living with Hope video and being asked directly to write about hopes and challenges. The Living with Hope video features family caregivers

Inhibitors,research,lifescience,medical and palliative patients’ discussion of hope and how they maintain hope. It is 15 minutes in length and was shown after baseline data was collected in the study. It is not known if this film had an influence on the content of the journals. Thus, journals may Inhibitors,research,lifescience,medical have been more ‘hopeful’ than if the caregivers had journaled without such prompts. This study is also limited due to the specificity of the targeted group of participants, who were female caregivers living in rural Western Canada, caring for a family member with advanced cancer. The literature on hope is inconclusive, with respect to whether women interpret or view hope differently than men. The caregiving experience may be different for men than women [54], so the findings

of Inhibitors,research,lifescience,medical our study may not be applicable to men caregivers. However this research brings forward a novel illustration of how hope is integrated throughout the caregiver’s experience. Conclusions This study has explored the hopes and challenges of rural female family caregivers of persons with advanced cancer. Inhibitors,research,lifescience,medical The journal entries participants completed as part of the LWHP provided insight into their daily lived experience,

and highlighted their emotional journey, the various challenges of caregiving, the way they employed self-care strategies, the various hopes they Inhibitors,research,lifescience,medical had and what fostered their hope. The concept of “hoping against hope” highlights the existence of tension and the possible co-existing contradictions with hope. At the same time that the participants are hoping for a cure, they are also hoping for their family member to have peace and comfort at the end of life. This research contributes to the much-needed assessment of P/EOL caregiver interventions, specifically those that impact hope and quality of life, and illustrates the value of a narrative approach Org 27569 to both research and practice [37]. ‘Hope against hope’ calls for researchers, health professionals and other supports in P/EOL care to encourage self-care strategies, self-reflection and social support to enhance caregivers’ hope and capacity to cope while caring for someone with a terminal Bosutinib concentration illness. There is an opportunity for health professionals and other P/EOL care supports in various settings to foster a relationship of trust with family caregivers in which their story can be told openly and in which they are holistically supported.

2009), and potentiation of BDNF binding

and signaling upon removal of polysialic acid (Burgess and Aubert 2006). L1 was first described as the NGF-inducible large external glycoprotein (NILE) (Bock et al. 1985; Prince et al. 1991). L1′s expression is clearly induced by NGF (Salton et al. 1983) but the mechanisms linking L1, NGF, and ChAT expression remain to be established. Blocking TrkA or p75NTR is known to abolish Inhibitors,research,lifescience,medical NGF-induced ChAT (Nonner et al. 2000). In contrast, NGF-induced L1 expression can occur in absence of p75NTR (Walsh et al. 1998) or independently of the high-affinity NGF receptor (Itoh et al. 1995). Our in vitro data clearly show that L1-Fc induces ChAT activity and future studies will investigate potential mechanisms. It is possible that L1′s activation of ChAT is carried out in part through FGFR (Maness Inhibitors,research,lifescience,medical and Schachner 2007), which is known to be a strong ChAT activator

(find more Grothe et al. 1989), which is similar to what we have found with C3d, an NCAM mimetic peptide (Burgess et al. 2009). In conclusion, L1 regulates the expression of ChAT, it influences levels of ChAT activity, and it is required for the proper development of septal cholinergic neurons in the first 2 postnatal weeks. It remains to be established whether improving cholinergic neurotransmission Inhibitors,research,lifescience,medical can rescue cognitive deficits in mice lacking L1. The promoting effects of L1 on ChAT activity and on the development of cholinergic neurons are of significance in the design of therapeutic strategies aiming to alleviate mental retardation and disorders of cholinergic deficits, as in Alzheimer’s disease. Acknowledgments This work was funded by Natural Science and Engineering Inhibitors,research,lifescience,medical Research Council of Canada (NSERCC), Canadian Institutes of Health Research (CIHR Funding Reference Number 93603), Canadian Neurotrauma Research Program (CNRP), Canada Foundation for Innovation (CFI), Ontario Innovation

Inhibitors,research,lifescience,medical Trust (OIT) (IA), Ontario Neurotrauma Foundation (ONF) Fellowship (IF), Ontario Mental Health Foundation (OMHF) Studentship (AB), and Fundação para a Ciência e a Tecnologia post-doctoral fellowship SFRH/BPD/14581/2003 (MTGdaC). M. Schachner is a New Jersey Professor of Spinal Cord Research. The authors found would also like to thank A. Tandon for his critical reading of the article; S. Bell for editing and proof-reading the article; MBF Bioscience and Geoff Greene for stereology support; A. Ypsilanti and S. Rideout for assistance in experiments; and G. Loers, I. Jakovcevski, and P. Putthoff for a generous supply of L1-Fc, reagents, and mice. We are grateful to W. B. Stallcup for the L1 antibody. We appreciated the expert assistance of G. Knowles at the Centre for Cytometry and Scanning Microscopy, and E. Yang at the Proteomics Core Facility of the Toronto Angiogenesis Research Centre, both located at the Sunnybrook Research Institute and supported by a CIHR Multi-User Equipment & Maintenance Grant.