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Objectives/Goals: The Wake Forest Clinical and Translational Science Institute (CTSI) has integrated academic goals of T0-T4 translation, scholarship, and education into our Academic Learning Health System (aLHS) framework. Our Translation Research Academy (TRA) provides rigorous training for outstanding and diverse K12 and early-career faculty to develop LHS core competencies. Methods/Study Population: The TRA Forum is the main vehicle for delivering an aLHS-oriented curriculum. Currently, the program includes six K12 scholars and 18 other early-career research faculty with facilitated access to CTSI resources. The TRA Forum is a 2-year seminar series that meets twice a month to discuss topics relevant to the aLHS, leadership, and career development. Inclusion of first- and second-year scholars facilitates peer mentorship, allowing Year 2 scholars to share insights with new scholars. Forum sessions are developed around adult learning theory: Each participant is asked to contribute their experience to discussions, and sessions focus on real-world examples. Results/Anticipated Results: Scholar and faculty commitment is very high. For the first 30 min., scholars present their work in small groups. This extends the range of disciplines exposed (64% of TRA graduates found this very helpful) and promotes translational traits of boundary crosser, team player, and systems thinker. Participants view the TRA as an opportunity to form internal peer networks, promote peer mentoring, and establish new collaborations. The remaining 60 minutes are used for education. Sessions include nominated topics and those providing a solid foundation in core aLHS competencies and characteristics of translational scientists. Educational sessions (97%) were rated as helpful or very helpful. Discussion/Significance of Impact: TRA scholars receive rigorous training in a highly supportive environment to produce aLHS researchers with skills to transcend boundaries, innovate systems, create new knowledge, and rigorously evaluate results.
Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Method
Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
Chapter 9 examines the real-time barriers to public health response that middle-income country demands caused in the context of Zika and MERS-CoV. The authors identify difficulties in identifying countries that possessed relevant biological samples and data, protracted negotiations over location, collaboration, and benefit sharing of research, and the development of standard agreements afterward that aimed at reducing transaction costs for access to crucial research inputs. This chapter drives home the implications of the changing system of pathogen sharing for US national security.
Reasoning ability has often been argued to be impaired in people with schizophrenic delusions, although evidence for this is far from convincing. This experiment examined the analogical reasoning abilities of several groups of patients, including non-deluded and deluded schizophrenics, to test the hypothesis that performance by the deluded schizophrenic group would be impaired.
Subjects/materials
Eleven deluded schizophrenics, 10 depressed subjects, seven non-deluded schizophrenics and 16 matched non-psychiatric controls, who were matched on a number of key variables, were asked to solve an analogical reasoning task.
Results
Performance by the deluded schizophrenic group was certainly impaired when compared with the depressed and non-psychiatric control groups though less convincingly so when compared with the non-deluded schizophrenic group. The impairment shown by the deluded schizophrenic group seemed to occur at the initial stage of the reasoning task.
Discussion
The particular type of impairment shown by the deluded subjects was assessed in relation to other cognitive problems already researched and the implications of these problems on reasoning tasks and theories of delusions was discussed.
We reviewed the recent literature for echocardiographic assessment of mitral valve abnormalities in children. A literature search was performed within the National Library of Medicine using the keywords “mitral regurgitation and/or stenosis, children.” The search was refined by adding the keywords “echocardiographic definition, classification, and evaluation.” Thirty-one studies were finally included. Significant advances in echocardiographic imaging of mitral valve defects, mainly due to the implementation of three-dimensional technology, contribute to a better understanding of the underlying anatomy. However, heterogeneity between classification systems of mitral valve disease severity is a serious problem. For regurgitant lesions, there is only very limited evidence from small studies that support the adoption of quantitative/semi-quantitative indexes commonly employed in adults. Despite the lack of evidence base, qualitative evaluation of regurgitation severity is often employed. For stenotic lesions, no clear categorisation based on trans-valvular echocardiography-derived “gradients” has been consistently applied to define mild, moderate, or severe obstruction across different paediatric age ranges. Quantitative parameters such as valve area have also been poorly validated in children. Adult recommendations are frequently applied without validation for the paediatric age. In conclusion, significant advances in the anatomical evaluation of mitral valve diseases have been made, thanks to three-dimensional echocardiography; however, limitations remain in the quantitative/semi-quantitative estimation of disease severity, both with respect to valvular regurgitation and stenosis. Because adult echocardiographic recommendations should not be simply translated to the paediatric age, more specific paediatric guidelines and standards for the assessment of mitral valve diseases are needed.
Advances in biomedical engineering have led to three-dimensional (3D)-printed models being used for a broad range of different applications. Teaching medical personnel, communicating with patients and relatives, planning complex heart surgery, or designing new techniques for repair of CHD via cardiac catheterisation are now options available using patient-specific 3D-printed models. The management of CHD can be challenging owing to the wide spectrum of morphological conditions and the differences between patients. Direct visualisation and manipulation of the patients’ individual anatomy has opened new horizons in personalised treatment, providing the possibility of performing the whole procedure in vitro beforehand, thus anticipating complications and possible outcomes. In this review, we discuss the workflow to implement 3D printing in clinical practice, the imaging modalities used for anatomical segmentation, the applications of this emerging technique in patients with structural heart disease, and its limitations and future directions.
New Zealand's ageing population and health inequities for Māori (Indigenous peoples) have prompted calls for innovative, culturally based approaches to improving health and wellbeing, and managing transitions in later life. This is particularly important for kaumātua (Māori elders) who, despite cultural strength and resilience, carry a significant burden in health, economic and social inequities. This paper describes the culture-centred development of a ‘tuakana‒teina’ (elder sibling‒younger sibling) peer support education programme designed to help kaumātua support other kaumātua experiencing transitions in later life. Taking a strengths-based approach that highlights ‘kaumātua mana motuhake’ (elder independence and autonomy), the study used kaupapa Māori (Māori approach, knowledge, skills, attitudes and values) and community-based participatory research methodology, to develop and pilot a culture-centred tuakana‒teina/peer education programme. Methods included establishing two advisory groups (one of kaumātua and one of sector experts); holding five focus groups with kaumātua; and running a pilot programme with 21 kaumātua. The findings demonstrate the value in a strengths-based approach that centralises Māori culture and kaumātua potential, capacity and ability, and recognises the continuing value and contribution of kaumātua to society. The study helps shift the focus from dominant stereotypes of ageing populations as a burden on society and shows the value of kaumātua supporting others during transitions in later life.
We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Methods
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Results
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
Conclusions
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Access to transition-related medical interventions (TRMIs) for transgender veterans has been the subject of substantial public interest and debate. To better inform these important conversations, the current study investigated whether undergoing hormone or surgical transition intervention(s) relates to the frequency of recent suicidal ideation (SI) and symptoms of depression in transgender veterans.
Methods
This study included a cross-sectional, national sample of 206 self-identified transgender veterans. They self-reported basic demographics, TRMI history, recent SI, and symptoms of depression through an online survey.
Results
Significantly lower levels of SI experienced in the past year and 2-weeks were seen in veterans with a history of both hormone intervention and surgery on both the chest and genitals in comparison with those who endorsed a history of no medical intervention, history of hormone therapy but no surgical intervention, and those with a history of hormone therapy and surgery on either (but not both) the chest or genitals when controlling for sample demographics (e.g., gender identity and annual income). Indirect effect analyses indicated that lower depressive symptoms experienced in the last 2-weeks mediated the relationship between the history of surgery on both chest and genitals and SI in the last 2-weeks.
Conclusions
Results indicate the potential protective effect that TRMI may have on symptoms of depression and SI in transgender veterans, particularly when both genitals and chest are affirmed with one's gender identity. Implications for policymakers, providers, and researchers are discussed.
The book consists of a volume of essays in honor of the outstanding sociologist, Edward A. Tiryakian; whose work has spanned a considerable number of countries, regions and topics. He has been highly influential, particularly in American and French sociology.
The contributors include such luminaries as Alan Sica, Bryan Turner, George Ritzer, John Simpson, Piotr Sztompka, Hans Joas, Roland Robertson and John Torpey.
The Sasanian Empire had many large, multicultural and typically heavily defended cities. Literary sources are filled with direct or indirect references to the deportation or internal transfer of populations from one region to another, and boosting the urban population was clearly an important part of imperial economic planning, but there has been relatively little study of Sasanian urbanism. This chapter provides a timely overview by re-examining the archaeological evidence for the physical appearance and distribution of some of these urban centres, discusses their forms, and uses Google imagery to locate two previously archaeologically unrecorded cities which feature in the Arab conquest and Heraclius’ campaign shortly before. It goes on to use the excavated evidence from three city sites in Iraq, Iran and Turkmenistan to illustrate the physical appearance of residential and/or commercial quarters, and concludes with some observations on the importance of the Sasanian urban economy.
INTRODUCTION
The term ‘Sasanian’ conjures a popular image of armoured knights, fire worshippers, courtly arts and conspicuous consumption, but a 400-year empire which stretched from Syria to Pakistan, recovered from the capture and death of one emperor on an eastern battlefield, and was one of Rome's biggest rivals and threats was not just built on exceptional kingship, feudalism and faith. Its success lay instead in effective bureaucracy and good management. Integrated planning for economic, military and civilian needs was fundamental, and without it the massive capital projects and military capabilities of the Sasanian state could not have been sustained. The huge number of mints known from marks on silver drachms implies a monetarised economy despite the fact that many of the mints are still physically unlocated. Moreover, many seals give the names of cities with which their owners were associated. The rapid movement of the Arab-led armies during the Islamic conquest was regularly punctuated by lengthy sieges and protracted negotiations with local commanders, which can be explained by the sheer number of cities and the scale of their defences.