Ageing makes us dyslexic

Background: The effects of typical ageing on spoken language are well known: word production is disproportionately affected while syntactic processing is relatively well preserved. Little is known, however, about how ageing affects reading.Aims: What effect does ageing have on written language processing? In particular, how does it affect our ability to read words? How does it affect phonological awareness (our ability to manipulate the sounds of our language)?Methods & Procedures: We tested 14 people with Parkinson's disease (PD), 14 typically ageing adults (TAA), and 14 healthy younger adults on a range of background neuropsychological tests and tests of phonological awareness. We then carried out an oral naming experiment where we manipulated consistency, and a nonword repetition task where we manipulated the word-likeness of the nonwords.Outcomes & Results: We find that normal ageing causes individuals to become mildly phonologically dyslexic in that people have difficulty pronouncing nonwords. People with Parkinson's disease perform particularly poorly on language tasks involving oral naming and metalinguistic processing. We also find that ageing causes difficulty in repeating nonwords. We show that these problems are associated with a more general difficulty in processing phonological information, supporting the idea that language difficulties, including poorer reading in older age, can result from a general phonological deficit.Conclusions: We suggest that neurally this age-induced dyslexia is associated with frontal deterioration (and perhaps deterioration in other regions) and cognitively to the loss of executive processes that enable us to manipulate spoken and written language. We discuss implications for therapy and treatment

International Classification of Functioning, Disability and Health Core Set construction in systemic sclerosis and other rheumatic diseases: a EUSTAR initiative

Objectives. To outline rationale and potential strategies for rheumatology experts to be able to develop disease-specific Core Sets under the framework of the International Classification of Functioning, Disability and Health (ICF). ICF is a universal framework introduced by the World Health Organization (WHO) to describe and quantify the impact and burden on functioning of health conditions associated with impairment/disability. Methods. A combined effort of the EULAR Scleroderma Clinical Trial and Research and the ICF Research Branch was initiated to develop an ICF language for scleroderma. From our Medline literature review, using the abbreviation and spelled out version of ICF, we assembled approaches and methodological reasoning for steps of core set development. Results. The ICF can be used for patient care and policy-making, as well as the provision of resources, services and funding. The ICF is used on institutional, regional, national and global levels. Several diseases now have ICF Core Sets. Patients with complex rheumatologic diseases will benefit from a disease-specific ICF Core Set and should be included in all stages of development. ICF Core Set development for rheumatic diseases can be conducted from a number of feasible strategies. Conclusion. This overview should help to clarify useful processes leading to development of an ICF Core Set, and also provide a platform for expert groups considering such an endeavou

Band 3 mutations, distal renal tubular acidosis, and Southeast Asian ovalocytosis

Band 3 mutations, distal renal tubular acidosis, and Southeast Asian ovalocytosis. Familial distal renal tubular acidosis (dRTA) and Southeast Asian ovalocytosis (SAO) may coexist in the same patient. Both can originate in mutations of the anion-exchanger 1 gene (AE1), which codes for band 3, the bicarbonate/chloride exchanger in both the red cell membrane and the basolateral membrane of the collecting tubule alpha-intercalated cell. Dominant dRTA is usually due to a mutation of the AE1 gene, which does not alter red cell morphology. SAO is caused by an AE1 mutation that leads to a nine amino acid deletion of red cell band 3, but by itself does not cause dRTA. Recent gene studies have shown that AE1 mutations are responsible for autosomal recessive dRTA in several countries in Southeast Asia; these patients may be homozygous for the mutation or be compound heterozygotes of two different AE1 mutations, one of which is usually the SAO mutation

Influence of vitamin D supplementation by sunlight or oral D3 on exercise performance

Purpose: To determine the relationship between vitamin D status and exercise performance in a large, prospective cohort study of young men and women across seasons (Study-1). Then, in a randomized, placebo-controlled trial, to investigate the effects on exercise performance of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol·L-1) by a unique comparison of safe, simulated-sunlight and oral vitamin D3 supplementation in wintertime (Study-2).  Methods: In Study-1, we determined 25(OH)D relationship with exercise performance in 967 military recruits. In Study-2, 137 men received either placebo, simulated-sunlight (1.3x standard erythemal dose in T-shirt and shorts, three-times-per-week for 4-weeks and then once-per-week for 8-weeks) or oral vitamin D3 (1,000 IU[BULLET OPERATOR]day-1 for 4-weeks and then 400 IU[BULLET OPERATOR]day-1 for 8-weeks). We measured serum 25(OH)D by LC-MS/MS and endurance, strength and power by 1.5-mile run, maximum-dynamic-lift and vertical jump, respectively.  Results: In Study-1, only 9% of men and 36% of women were vitamin D sufficient during wintertime. After controlling for body composition, smoking and season, 25(OH)D was positively associated with endurance performance (P ≤ 0.01, [INCREMENT]R2 = 0.03–0.06, small f2 effect sizes): 1.5-mile run time was ~half-a-second faster for every 1 nmol·L-1 increase in 25(OH)D. No significant effects on strength or power emerged (P > 0.05). In Study-2, safe simulated-sunlight and oral vitamin D3 supplementation were similarly effective in achieving vitamin D sufficiency in almost all (97%); however, this did not improve exercise performance (P > 0.05).  Conclusion: Vitamin D status was associated with endurance performance but not strength or power in a prospective cohort study. Achieving vitamin D sufficiency via safe, simulated summer sunlight or oral vitamin D3 supplementation did not improve exercise performance in a randomized-controlled trial

Enhancing Quality and Impact of Early Phase Dose-Finding Clinical Trial Protocols:The SPIRIT DoseFinding Extension (SPIRIT-DEFINE) Guidance The SPIRIT-DEFINE Statement

International audienc

Enhancing Reporting Quality and Impact of Early Phase Dose-Finding Clinical Trials:The CONSORT Dose-Finding Extension (CONSORT-DEFINE) Guidance The CONSORT-DEFINE Statement

International audienceThe CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development. These trials are often inadequately reported, hampering their informativeness and making evidence informed decisions difficult. The CONSORT-DEFINE guidance aims to develop an international, consensus driven guideline for reporting early phase dose-finding trials to promote transparency, completeness, reproducibility, and facilitate the interpretation of the results. The CONSORT-DEFINE guidance provides recommendations for essential items that should be reported in early phase dose-finding trials to promote greater clarity, reproducibility, informativeness, and usefulness of results