Empowering patients, empowering clinicians: How the lessons of HIV can inform chronic disease management across the primary healthcare system

No Abstrac

Sexual reproductive healthcare utilisation and HIV testing in an integrated adolescent youth centre clinic in Cape Town, South Africa

Background: HIV prevalence is increasing among South African youth, but HIV counselling and testing (HCT) remains low. Adolescent pregnancy rates are also high. Objectives: Innovative strategies are needed to increase HIV and pregnancy screening and prevention among youth. Method: The Desmond Tutu HIV Foundation Youth Centre (DTHF-YC) offers integrated, incentivised sexual and reproductive health (SRH), educational and recreational programmes. We compared HCT and contraception rates between the DTHF-YC and a public clinic (PC) in Cape Town to estimate the impact of DTHF-YC on youth contraception and HCT utilisation. Results: In 2015, females < 18 years had 3.74 times (confidence interval [CI]: 3.37–4.15) more contraception visits at DTHF-YC versus PC. There were no differences in the contraception and adherence was suboptimal. DTHF-YC youth (aged 15–24 years) were 1.85 times (CI: 1.69–2.01) more likely to undergo HCT versus PC, while male youth were 3.83 times (CI: 3.04–4.81) more likely to test at DTHF-YC. Youth were a third less likely to test HIV-positive at DTHF-YC versus PC. Female sex, older age, clinic attendance for contraception and sexually transmitted infections (STIs), redeeming incentives and high DTHF-YC attendance were all independent factors associated with increased HCT. Conclusion: Youth were significantly more likely to access SRH services at DTHF-YC compared with the PC. The differences were greatest in contraception use by female adolescents < 18 years and HCT by male youth. Increased HCT did not increase youth HIV case detection. Data from DTHF-YC suggest that youth-friendly healthcare providers integrated into community youth spaces may increase youth HCT and contraception rates

BAD: a good therapeutic target?

The major goal in cancer treatment is the eradication of tumor cells. Under stress conditions, normal cells undergo apoptosis; this property is fortunately conserved in some tumor cells, leading to their death as a result of chemotherapeutic and/or radiation-induced stress. Many malignant cells, however, have developed ways to subvert apoptosis, a characteristic that constitutes a major clinical problem. Gilmore et al. recently described the ability of ZD1839, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), to induce apoptosis of mammary cells that are dependent upon growth factors for survival. Furthermore, they showed that the major effector of the EGFR-targeted therapy is BAD, a widely expressed BCL-2 family member. These results are promising in light of the role of the EGFR in breast cancer development

Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium

Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (< 2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation

Influence of firm size on the competencies required to management engineers in the Jordanian telecommunications sector

This is an Accepted Manuscript of an article published by Taylor & Francis in European Journal of Engineering Education on [13 jun 2016], available online:http://www.tandfonline.com/ doi/abs/10.1080/03043797.2016.1197890.[EN] The objective of this study is to identify the competencies required to achieve success in the transition from higher education to the labour market based on the perceptions of employers. This paper analyses the assessments made by a group of engineering company employers. An item-battery of 20 competencies was grouped into 3 dimensions by using factor analysis. Subsequently, respondents scores were also clustered into three groups and characterised through contingency tables. The competencies demanded by employers were grouped into business and finance, problem-solving and strategic planning. Significant differences were found between responses from employers working in medium and small companies, who placed more importance on competencies related to problem-solving and strategic planning, and employers in big companies, who were more concerned about the difficulties of finding well-trained graduates. The findings from this paper have important implications for research in the areas of higher education and organisations that usually employ graduate engineers.The authors would like to thank the Education, Audiovisual and Culture Executive Agency (EACEA) [Tempus program. Project number 511074] of the European Commission for providing funding for conducting this study. This publication reflects the views only of the authors, and the Commission cannot be held responsible for any use which may be made of the information contained therein.Conchado Peiró, A.; Bas Cerdá, MDC.; Gharaibeh, KM.; Kaylani, H. (2016). Influence of firm size on the competencies required to management engineers in the Jordanian telecommunications sector. European Journal of Engineering Education. 1-14. doi:10.1080/03043797.2016.1197890S114ALLEN, J., & DE WEERT, E. (2007). What Do Educational Mismatches Tell Us About Skill Mismatches? A Cross-country Analysis. European Journal of Education, 42(1), 59-73. doi:10.1111/j.1465-3435.2007.00283.xBarrella, E. M., & Buffinton, K. W. (2009). Corporate Assessment of Strategic Issues in Technology Management. Engineering Management Journal, 21(1), 27-33. doi:10.1080/10429247.2009.11431795Bartram, D., Lindley, P. A., Marshall, L., & Foster, J. (1995). The recruitment and selection of young people by small businesses. Journal of Occupational and Organizational Psychology, 68(4), 339-358. doi:10.1111/j.2044-8325.1995.tb00592.xBehrends, T. (2007). Recruitment Practices in Small and Medium Size Enterprises. An Empirical Study among Knowledge-intensive Professional Service Firms. management revu, 18(1), 55-74. doi:10.5771/0935-9915-2007-1-55Boshuizen, H. P. A. (s. f.). Does Practice Make Perfect? Innovation and Change in Professional Education, 73-95. doi:10.1007/1-4020-2094-5_5Branine, M. (2008). Graduate recruitment and selection in the UK. Career Development International, 13(6), 497-513. doi:10.1108/13620430810901660Butler, C. J., & Chinowsky, P. S. (2006). Emotional Intelligence and Leadership Behavior in Construction Executives. Journal of Management in Engineering, 22(3), 119-125. doi:10.1061/(asce)0742-597x(2006)22:3(119)Carbone, T. A., & Gholston, S. (2004). Project Manager Skill Development: A Survey of Programs and Practitioners. Engineering Management Journal, 16(3), 10-16. doi:10.1080/10429247.2004.11415252Cassell, C., Nadin, S., Gray, M., & Clegg, C. (2002). Exploring human resource management practices in small and medium sized enterprises. Personnel Review, 31(6), 671-692. doi:10.1108/00483480210445962Cattell, R. B., & Vogelmann, S. (1977). A Comprehensive Trial Of The Scree And Kg Criteria For Determining The Number Of Factors. Multivariate Behavioral Research, 12(3), 289-325. doi:10.1207/s15327906mbr1203_2Chan, A. P. C., Ho, D. C. K., & Tam, C. M. (2001). Effect of Interorganizational Teamwork on Project Outcome. Journal of Management in Engineering, 17(1), 34-40. doi:10.1061/(asce)0742-597x(2001)17:1(34)Coll, R. K., & Zegwaard, K. E. (2006). Perceptions of desirable graduate competencies for science and technology new graduates. Research in Science & Technological Education, 24(1), 29-58. doi:10.1080/02635140500485340Cronbach, L. J. (1951). Coefficient alpha and the internal structure of tests. Psychometrika, 16(3), 297-334. doi:10.1007/bf02310555Dekker, R., de Grip, A., & Heijke, H. (2002). The effects of training and overeducation on career mobility in a segmented labour market. International Journal of Manpower, 23(2), 106-125. doi:10.1108/01437720210428379Elfenbein, D. W., Hamilton, B. H., & Zenger, T. R. (2010). The Small Firm Effect and the Entrepreneurial Spawning of Scientists and Engineers. Management Science, 56(4), 659-681. doi:10.1287/mnsc.1090.1130Farr, J. V., & Brazil, D. M. (2009). Leadership Skills Development for Engineers. Engineering Management Journal, 21(1), 3-8. doi:10.1080/10429247.2009.11431792Garen, J. E. (1985). Worker Heterogeneity, Job Screening, and Firm Size. Journal of Political Economy, 93(4), 715-739. doi:10.1086/261327Gharaibeh, K. M., Kaylani, H., Murphy, N., Brennan, C., Itradat, A., Al-Bataineh, M., … Bany Salameh, H. (2014). A Masters Programme in telecommunications management – demand-based curriculum design. European Journal of Engineering Education, 40(3), 267-284. doi:10.1080/03043797.2014.944104Hayes, J., Rose‐Quirie, A., & Allinson, C. W. (2000). Senior managers’ perceptions of the competencies they require for effective performance: implications for training and development. Personnel Review, 29(1), 92-105. doi:10.1108/00483480010295835Hersch, J. (1991). Education Match and Job Match. The Review of Economics and Statistics, 73(1), 140. doi:10.2307/2109696Hoegl, M., & Parboteeah, K. P. (2007). Creativity in innovative projects: How teamwork matters. Journal of Engineering and Technology Management, 24(1-2), 148-166. doi:10.1016/j.jengtecman.2007.01.008Hoegl, M., Praveen Parboteeah, K., & Gemuenden, H. G. (2003). When teamwork really matters: task innovativeness as a moderator of the teamwork–performance relationship in software development projects. Journal of Engineering and Technology Management, 20(4), 281-302. doi:10.1016/j.jengtecman.2003.08.001Van Hoorn, T. P. (1979). Strategic planning in small and medium-sized companies. Long Range Planning, 12(2), 84-91. doi:10.1016/0024-6301(79)90076-1HUSELID, M. A. (1995). THE IMPACT OF HUMAN RESOURCE MANAGEMENT PRACTICES ON TURNOVER, PRODUCTIVITY, AND CORPORATE FINANCIAL PERFORMANCE. Academy of Management Journal, 38(3), 635-672. doi:10.2307/256741Kaiser, H. F. (1958). The varimax criterion for analytic rotation in factor analysis. Psychometrika, 23(3), 187-200. doi:10.1007/bf02289233Kaufman, L., & Rousseeuw, P. J. (Eds.). (1990). Finding Groups in Data. Wiley Series in Probability and Statistics. doi:10.1002/9780470316801Krug, J. (1997). People Skills: Teamwork. Journal of Management in Engineering, 13(2), 15-16. doi:10.1061/(asce)0742-597x(1997)13:2(15)Male, S. A., Bush, M. B., & Chapman, E. S. (2010). Perceptions of Competency Deficiencies in Engineering Graduates. Australasian Journal of Engineering Education, 16(1), 55-68. doi:10.1080/22054952.2010.11464039Mao, X., Zhang, X., & AbouRizk, S. M. (2009). Enhancing Value Engineering Process by Incorporating Inventive Problem-Solving Techniques. Journal of Construction Engineering and Management, 135(5), 416-424. doi:10.1061/(asce)co.1943-7862.0000001Mendelsohn, R. (1998). Teamwork—The Key to Productivity. Journal of Management in Engineering, 14(1), 22-25. doi:10.1061/(asce)0742-597x(1998)14:1(22)Moore, B. V. (1921). Personnel selection of graduate engineers: The differentiation of apprentice engineers for training as salesmen, designers, and executives of production. Psychological Monographs, 30(5), i-85. doi:10.1037/h0093191Moy, J. W., & Lee, S. M. (2002). The career choice of business graduates: SMEs or MNCs? Career Development International, 7(6), 339-347. doi:10.1108/13620430210444367Nair, C. S., Patil, A., & Mertova, P. (2009). Re-engineering graduate skills – a case study. European Journal of Engineering Education, 34(2), 131-139. doi:10.1080/03043790902829281Passow, H. J. (2012). Which ABET Competencies Do Engineering Graduates Find Most Important in their Work? Journal of Engineering Education, 101(1), 95-118. doi:10.1002/j.2168-9830.2012.tb00043.xPinnington, A. H. (2011). Competence development and career advancement in professional service firms. Personnel Review, 40(4), 443-465. doi:10.1108/00483481111133336Reio, T. G., & Sutton, F. C. (2006). Employer assessment of work-related competencies and workplace adaptation. Human Resource Development Quarterly, 17(3), 305-324. doi:10.1002/hrdq.1176Robar, T. Y. (1998). Communication and Career Advancement. Journal of Management in Engineering, 14(2), 26-28. doi:10.1061/(asce)0742-597x(1998)14:2(26)Rowold, J., & Kauffeld, S. (2008). Effects of career‐related continuous learning on competencies. Personnel Review, 38(1), 90-101. doi:10.1108/00483480910920732Ruiz-Mercader, J., Meroño-Cerdan, A. L., & Sabater-Sánchez, R. (2006). Information technology and learning: Their relationship and impact on organisational performance in small businesses. International Journal of Information Management, 26(1), 16-29. doi:10.1016/j.ijinfomgt.2005.10.003Soliman, F., & Spooner, K. (2000). Strategies for implementing knowledge management: role of human resources management. Journal of Knowledge Management, 4(4), 337-345. doi:10.1108/13673270010379894Srour, I., Abdul-Malak, M.-A., Itani, M., Bakshan, A., & Sidani, Y. (2013). Career Planning and Progression for Engineering Management Graduates: An Exploratory Study. Engineering Management Journal, 25(3), 85-100. doi:10.1080/10429247.2013.11431985Sunindijo, R. Y., Hadikusumo, B. H., & Ogunlana, S. (2007). Emotional Intelligence and Leadership Styles in Construction Project Management. Journal of Management in Engineering, 23(4), 166-170. doi:10.1061/(asce)0742-597x(2007)23:4(166)Tanova, C. (2003). Firm size and recruitment: staffing practices in small and large organisations in north Cyprus. Career Development International, 8(2), 107-114. doi:10.1108/13620430310465534Teichler, U. (1999). Higher education policy and the world of work: changing conditions and challenges. Higher Education Policy, 12(4), 285-312. doi:10.1016/s0952-8733(99)00019-7Tsang, M. C., & Levin, H. M. (1985). The economics of overeducation. Economics of Education Review, 4(2), 93-104. doi:10.1016/0272-7757(85)90051-2Ward, J. H. (1963). Hierarchical Grouping to Optimize an Objective Function. Journal of the American Statistical Association, 58(301), 236-244. doi:10.1080/01621459.1963.10500845Zenger, T. R. (1994). Explaining Organizational Diseconomies of Scale in R&D: Agency Problems and the Allocation of Engineering Talent, Ideas, and Effort by Firm Size. Management Science, 40(6), 708-729. doi:10.1287/mnsc.40.6.708Zenger, T. R., & Lazzarini, S. G. (2004). Compensating for innovation: Do small firms offer high-powered incentives that lure talent and motivate effort? Managerial and Decision Economics, 25(67), 329-345. doi:10.1002/mde.119

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

n/

Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1

Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region

Accounting for Extreme Events in the Economic Assessment of Climate Change

Extreme events are one of the main channels through which climate and socio- economic systems interact. It is likely that climate change will modify their probability distributions and their consequences. The long-term growth models used in climate change assessments, however, cannot capture the effects of short-term shocks; they thus model extreme events in a very crude manner. To assess the importance of this limitation, a non-equilibrium dynamic model (NEDyM) is used to model the macroeconomic consequences of extreme events. Its conclusions are the following: (i) Dynamic processes multiply the extreme event direct costs by a factor 20; half of this increase comes from short-term processes; (ii) A possible modication of the extreme event distribution due to climate change can be responsible for significant GDP losses; (iii) The production losses caused by extreme events depend, with strong non-linearity, both on the changes in the extreme distribution and on the ability to fund the rehabilitation after each disaster. These conclusions illustrate that the economic assessment of climate change does not only depend on beliefs on climate change but also on beliefs on the economy. Moreover, they suggest that averaging short-term processes like extreme events over the five- or ten-year time step of a classical long-term growth model can lead to inaccurately low assessments of the climate change damages

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes