A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham elderly thyroid study

Context: Subclinical hypothyroidism (SCH) and cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit. Objective: Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function. Design and Setting: We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. Patients: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. Intervention: T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 µg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 females, 21 males; mean age 73.5 yr, range 65–94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66–84 yr). Main Outcome Measures: Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. Results: Eighty-two percent and 84% in the T4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months. Conclusions: This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.

Services for activities in group editing 'sage'

The project described in this thesis investigates the needs of a group of people working cooperatively in an OSI environment, and recommends tools and services to meet these needs. The project looks specifically at Services for Activities in Group Editing, and is identified as the `SAGE' project. The project uses case studies to identify user requirements and to determine common functionalities for a variety of group editing activities. A prototype is implemented in an X.400 environment to help refine user requirements, as a source of new ideas and to test the proposed functionalities. The conceptual modelling follows current CCITT proposals, but a new classification of group activities is proposed: Informative, Objective and Supportive application groups. It is proposed that each of these application groups have their own Service Agent. Use of this classification allows the possibility of developing three sets of tools which will cover a wide range of group activities, rather than developing tools for individual activities. Group editing is considered to be in the Supportive application group. A set of additional services and tools to support group editing are proposed in the context of the CCITT draft on group communication, X.gc. The proposed services and tools are mapped onto the X.400 series of recommendations, with the Abstract Service Definition of the operational objects defined, along with their associated component files, by extending the X.420 protocol functionality. It is proposed that each of the Informative, Objective and Supportive application groups should be implemented as a modified X.420 inter-personal messaging system.

Cholinesterase inhibitors for Parkinson's disease dementia

Background - The loss of cholinergic, dopaminergic and noradrenergic innervations seen in Parkinson's Disease Dementia (PDD) suggest a potential role for cholinesterase inhibitors. Concerns have been expressed about a theoretical worsening of Parkinson's disease related symptoms, particularly movement symptoms. Objectives - To assess the efficacy, safety, tolerability and health economic data relating to the use of cholinesterase inhibitors in PDD. Search methods - The trials were identified from the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 19 April 2005 using the search term parkinson*. This register contains records from major health care databases and many ongoing trial databases and is updated regularly. Comprehensive searches of abstracts from major scientific meetings were performed. Pharmaceutical companies were approached for information regarding additional and ongoing studies. Selection criteria - Randomized, double-blind, placebo-controlled studies assessing the effectiveness of cholinesterase inhibitors in PDD. Inclusion and exclusion criteria were stated to limit bias. Data collection and analysis - Two reviewers (IM, CF) independently reviewed the quality of the studies utilizing criteria from the Cochrane Collaboration Handbook. Medications were examined separately and as a group. The outcome measures assessed were in the following domains: neuropsychiatric features, cognition, global impression, daily living activities, quality of life, burden on caregiver, Parkinsonian related symptoms, treatment acceptability as determined by withdrawal from trials, safety as determined by the frequency of adverse events, institutionalisation, death and health economic factors. Main results - A detailed and systematic search of relevant databases identified one published randomized, double-blind, placebo-controlled study (Emre 2004) involving 541 patients that compared rivastigmine with placebo. Rivastigmine produced statistically significant improvements in several outcome measures. On the primary cognitive measure, the ADAS-Cog, rivastigmine was associated with a 2.80 point ADAS-Cog improvement [WMD -2.80, 95% Cl -4.26 to -1.34, P = 0.0002] and a 2.50 point ADCS-ADL improvement [95% Cl 0.43 to 4.57, P = 0.02] relative to placebo. Clinically meaningful (moderate or marked) improvement occurred in 5.3% more patients on rivastigmine, and meaningful worsening occurred in 10.1% more patients on placebo. Tolerability appeared to be a significant issue. Significantly more patients on rivastigmine dropped out of the study due to adverse events [62/362 versus 14/179, OR 2.44, 95% Cl 1.32 to 4.48, P = 0.004]. Nausea [20/179 versus 105/362, OR 3.25, 95% Cl 1.94 to 5.45, P < 0.00001], tremor [7/179 versus 37/362, OR 2.80, 95% Cl 1.22 to 6.41, P = 0.01] and in particular vomiting [3/179 versus 60/362, OR 11.66, 95% Cl 3.60 to 37.72, P < 0.0001] were significantly more common with rivastigmine. However, significantly fewer patients died on rivastigmine than placebo [4/362 versus 7/179, OR 0.27, 95% CI 0.08 to 0.95, P = 0.04] Authors' conclusions - Rivastigmine appears to improve cognition and activities of daily living in patients with PDD. This results in clinically meaningful benefit in about 15% of cases. There is a need for more studies utilising pragmatic measures such as time to residential care facility and both patient and carer quality of life assessments. Future trials should involve other cholinesterase inhibitors, utilise tools to analyse the data that limit any bias and measure health economic factors. It is unlikely that relying solely on the last observation carried forward (LOCF) is sufficient. Publication of the observed case data in the largest trial would assist (Emre 2004). Adverse events were associated with the cholinergic activity of rivastigmine, but may limit patient acceptability as evidenced by the high drop out rate in the active arm.

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala8-substituted analogues of GLP-1, (Abu8)GLP-1 and (Val8)GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu8)GLP-1 and (Val8)GLP-1 exhibited moderate affinities (IC50: 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC50: 0.37 nM). (Abu8)GLP-1 and (Val8)GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val8)GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu8 )GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val8)GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala8 in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val8)GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

Entrepreneurship in the neighborhood:shifting patterns of economic activities in residential neighborhoods in five dutch cities

Cities are oftentimes seen as undergoing a process of "emergence" in the "new economy." However, this process has largely remained empirically underdetermined. This article examines the intra-city geography of emerging businesses in newly dominant sectors of the urban economy. The change in dominant sectors coincides with a shift towards small- and medium-sized businesses, creating new economic opportunities for urban residential areas. The residential neighborhood is introduced as a place where supply and demand side drivers operate to attract or limit such new economic activity. Allen Scott's perspective of the cognitive-cultural economy is used to analyze which neighborhoods are flourishing sites of the cognitive-cultural sectors. His perspective on industries that are on the rise in urban environments and their growth potential proves very valuable. Social demographic characteristics on the level of the neighborhood are used as predictors of the composition of the local economy. The analyses show that in particular wealthy, gentrified neighborhoods are more prone than others to becoming "hubs" of the cognitive-cultural economy. However, disadvantaged neighborhoods may under certain conditions serve as incubators for business start-ups as they offer low-rent office spaces. This has important consequences for their future economic growth potential as well as the distribution of successful businesses in the city. © 2013 Urban Affairs Association.

MINERVA – the Ministerial Network for Valorising Activities in Digitisation Towards an Agreed European Platform for Digitisation of Cultural and Scientific Heritage

MINERVA is a project funded by the European Commission IST Programme within the 5th Framework Programme. It created a network of EU Ministries and other agencies in charge of cultural policies and programmes, which is open to enlargement to new countries and new sectors of the civil society. The network discusses, correlates and harmonises the activities carried out in the field of digitisation of cultural and scientific heritage, aiming at creating a common European platform made up of agreed recommendations, guidelines, standards. The network acts also to foster collaboration between European Commission and Member States, to ensure awareness of European policies at national level, to exchange good practice, to coordinate national programmes in order to embed in national digitisation activities the technical results achieved by the network. Some main outcomes of the activities are presented.

Health related quality of life and perception of stigmatisation in adolescents living with sickle cell disease in Nigeria:a cross sectional study

Background: Sickle cell disease impacts the physical, emotional and psychological aspects of life of the affected persons, often times exposing them to disease associated stigma from the society and alters the health related quality of life (HRQoL). This study compared the HRQoL of adolescents with sickle cell disease with their healthy peers, identified socio-demographic and clinical factors impacting HRQoL, and determined the extent and effects of SCD related stigma on quality of life. Procedure: We conducted a cross-sectional survey among 160 adolescents, 80 with SCD and 80 adolescents without SCD. Socio-demographic and clinical data were collected using a pre-tested questionnaire. HRQoL was investigated using the Short Form (SF-36v2) Health Survey. SCD perceived stigma was measured using an adaptation of a perceived stigma questionnaire. Results: Adolescents with SCD have significantly worse HRQoL than their peers in all of the most important dimensions of HRQoL (physical functioning, physical roles limitation, emotional roles limitation, social functioning, bodily pain, vitality and general health perception) except mental health. Recent hospital admission and SCD related complication further lowered HRQoL scores. Over seventy percent of adolescents with SCD have moderate to high level of perception of stigmatisation. Hospitalisation, SCD complication, SCD stigma were inversely, and significantly associated with HRQoL. Conclusions: Adolescents living with SCD in Nigeria have lower health related quality of life compared to their healthy peers. They also experience stigma that impacts their HRQoL. Complications of SCD and hospital admissions contribute significantly to this impairment. Pediatr Blood Cancer 2015;62:1245-1251.

The Use of the Military for Law Enforcement Activities in Central America

Faced with the violence, criminality and insecurity now threatening peace and democratic governance in Central America, the region’s governments have decided to use the Armed Forces to carry out actions in response to criminal actions, looking to improve their performance. Although public demand for including the Armed Forces in these functions takes place within a legally legitimate framework, it is motivated by tangible circumstances such as increased levels of violence, delinquency and crime. Despite being coupled with the perception of institutional weakness within the security and judicial system (particularly police) and the recognition of prestige, efficiency, discipline and severity in fulfilling the Armed Forces’ missions, these arguments are insufficient to legitimize the use of the military as a police force. Within this context, this paper reflects on the implications or consequences of the use of the Armed Forces in duties traditionally assigned to the police in the Central American region with the goal of contributing to the debate on this topic taking place in the Americas. To achieve this end, first we will focus on understanding the actual context in which a decision is made to involve the Armed Forces in security duties in the region. Second, we will examine the effects and implications of this decision on the Armed Forces’ relations within their respective societies. Third and finally, considering this is already a reality in the region, this paper will provide recommendations. The main findings of this research, resulting from the application of an analyticaldescriptive and historically based study, are organized in three dimensions: the political dimension, by implication referring to the relationship between the ultimate political authority and the Armed Forces; the social dimension, by implication the opinion of citizens; and other implications not only affecting the structural and cultural organization of armies and police but also the complementary operational framework within a context of comprehensive response by the State. As a main conclusion, it poses there is an environment conducive to the use of the Armed Forces in citizen’s security, in view of the impact of threats provoked by criminal structures of a military nature currently operating in Central America. However, this participation creates an inevitable social and political impact if implemented in isolation or given a political leading role and/or operational autonomy. This participation poses risks to the institutions of the Armed Forces and the police as well. Finally, this paper identifies an urgent need for the Armed Forces’ role to be more clearly defined with regard to security matters, limiting it to threats that impact States’ governability and existence. Nonetheless, Central American States should seek a COMPREHENSIVE response to current crime and violence, using all necessary institutions to confront these challenges, but with defined roles and responsibilities for each and dynamic coordination to complement their actions.