Subclinical hypothyroidism in community-dwelling older people: consequences and treatment outcomes

The thyroid gland plays a crucial role in regulating nearly all bodily processes. A particular state of thyroid function, dubbed subclinical hypothyroidism (with high thyroid-stimulating hormone [TSH] and normal free thyroid hormone [fT4] in blood tests), becomes more prevalent with advancing age and it is unclear how this condition should be interpreted in community-dwelling older people (arbitrarily 65 years and older). Whether or not the condition is associated with negative health consequences, and whether treatment with levothyroxine (artificial thyroid hormone) is warranted, are subjects of decades-long debate. This thesis aims to identify whether subclinical hypothyroidism is associated with a range of relevant outcomes, and whether levothyroxine treatment leads to benefits, in community-dwelling older persons. The results in this thesis demonstrate that subclinical hypothyroidism is not associated with clinically (e.g. physical and cognitive function, mood or mortality risk) or biologically (e.g. thyroid antibodies or anaemia) relevant outcomes. Levothyroxine treatment does not provide benefits. These results suggest that subclinical hypothyroidism in older people is a strictly biochemical diagnosis, they support more conservative diagnostic approaches and do not support routine treatment with levothyroxine. More research is needed before extrapolating to more specific subgroups and to assess whether international guidelines should be updated.SBO

Source parameters of the great Sumatran megathrust earthquakes of 1797 and 1833 inferred from coral microatolls

Large uplifts and tilts occurred on the Sumatran outer arc islands between 0.5° and 3.3°S during great historical earthquakes in 1797 and 1833, as judged from relative sea level changes recorded by annually banded coral heads. Coral data for these two earthquakes are most complete along a 160-km length of the Mentawai islands between 3.2° and 2°S. Uplift there was as great as 0.8 m in 1797 and 2.8 m in 1833. Uplift in 1797 extended 370 km, between 3.2° and 0.5°S. The pattern and magnitude of uplift imply megathrust ruptures corresponding to moment magnitudes (M_w) in the range 8.5 to 8.7. The region of uplift in 1833 ranges from 2° to at least 3.2°S and, judging from historical reports of shaking and tsunamis, perhaps as far as 5°S. The patterns and magnitude of uplift and tilt in 1833 are similar to those experienced farther north, between 0.5° and 3°N, during the giant Nias-Simeulue megathrust earthquake of 2005; the outer arc islands rose as much as 3 m and tilted toward the mainland. Elastic dislocation forward modeling of the coral data yields megathrust ruptures with moment magnitudes ranging from 8.6 to 8.9. Sparse accounts at Padang, along the mainland west coast at latitude 1°S, imply tsunami runups of at least 5 m in 1797 and 3–4 m in 1833. Tsunamis simulated from the pattern of coral uplift are roughly consistent with these reports. The tsunami modeling further indicates that the Indian Ocean tsunamis of both 1797 and 1833, unlike that of 2004, were directed mainly south of the Indian subcontinent. Between about 0.7° and 2.1°S, the lack of vintage 1797 and 1833 coral heads in the intertidal zone demonstrates that interseismic submergence has now nearly equals coseismic emergence that accompanied those earthquakes. The interseismic strains accumulated along this reach of the megathrust have thus approached or exceeded the levels relieved in 1797 and 1833

Conciencia fonológica, memoria fonológica y velocidad de denominación, en niños con problemas de aprendizaje de la lectura.

El objetivo de la presente investigación es analizar si 35 niños de segundo grado de primaria con dislexia presentan dificultades en habilidades implicadas en el procesamiento fonológico, como son la conciencia fonológica, la memoria de trabajo fonológica y la velocidad de denominación. Los niños fueron evaluados en diferentes tareas de conciencia fonológica, en la repetición de palabras y pseudopalabras de diferente metría, y en tareas de denominación de imágenes y números. Nuestros resultados muestran que el 77% de los niños tuvo dificultades para procesar pseudopalabras frecuentes y el 68, 6% para pseudopalabras no frecuentes; Por otro lado, el 85,7% presento lentitud en las tareas de denominación. Se concluye que, en los niños con dislexia, existen limitaciones en la memoria de trabajo fonológica y lentitud para acceder las representaciones almacenadas en la memoria a largo plazo. En contraste, el 100% de los niños evaluados no mostró dificultades a nivel de conciencia fonológica. Se discute sobre las implicancias de estos resultados, así como sobre las razones por las cuales consideramos que estos niños, a pesar de sus dificultades lectoras, habrían presentado un adecuado desempeño en las tareas de conciencia fonológica.The aim of the present empiric study is to examine whether 35 second grade children with dyslexia exhibit impairments in phonological abilities such as phonological awareness, working memory and naming speed. Children were tested in several phonological awareness tasks; processing nonsense and familiar words from one to four syllables; and naming pictures and numbers. Results showed that 77% of children presented troubles in the ability of repeating frequent nonsense words and 68, 6% presented troubles in repeating infrequent nonsense words. In contrast, 85,7% of children were slow in naming tasks. These findings suggest that dyslexia children exhibit a deficit in working memory and in naming speed. Regarding phonological awareness, 100% of children demonstrated to have phonological awareness abilities. Theoretical and practical implications are discussed, including the reasons why we consider these children presented an adequate phonological awareness performance even though their reading impariements.Tesi

Validation of reference genes for quantitative RT-PCR studies in porcine oocytes and preimplantation embryos

<p>Abstract</p> <p>Background</p> <p>In the developing embryo, total RNA abundance fluctuates caused by functional RNA degradation and zygotic genome activation. These variations in the transcriptome in early development complicate the choice of good reference genes for gene expression studies by quantitative real time polymerase chain reaction.</p> <p>Results</p> <p>In order to identify stably expressed genes for normalisation of quantitative data, within early stages of development, transcription levels were examined of 7 frequently used reference genes (<it>B2M, BACT, GAPDH, H2A, PGK1, SI8</it>, and <it>UBC</it>) at different stages of early porcine embryonic development (germinal vesicle, metaphase-2, 2-cell, 4-cell, early blastocyst, expanded blastocyst). Analysis of transcription profiling by geNorm software revealed that <it>GAPDH, PGK1, S18</it>, and <it>UBC </it>showed high stability in early porcine embryonic development, while transcription levels of <it>B2M, BACT</it>, and <it>H2A </it>were highly regulated.</p> <p>Conclusion</p> <p>Good reference genes that reflect total RNA content were identified in early embryonic development from oocyte to blastocyst. A selection of either <it>GAPDH </it>or <it>PGK1</it>, together with ribosomal protein <it>S18 </it>(<it>S18</it>), and <it>UBC </it>is proposed as reference genes, but the use of <it>B2M, BACT</it>, or <it>H2A </it>is discouraged.</p

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Background: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. Methods: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. Discussion: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date

Factores que inhiben el uso de plataformas de autoservicio en el retail

La presente tesis de investigaci?n tiene como objetivo evaluar e identificar los factores que inhiben la compra en los kioscos digitales dentro de las tiendas f?sicas de retail. Esta investigaci?n est? enfocada en el caso de Falabella Per?, que forma parte del Grupo Falabella, una de las tiendas por departamento l?deres del sector retail del pa?s. Adem?s, una de las m?s importantes y consolidadas a nivel de Am?rica Latina. Comercializa diversas categor?as de productos de consumo masivo como son, textil, l?nea blanca, calzado, entre otras a nivel nacional. Esta investigaci?n est? enfocada principalmente en una de sus principales tiendas como es la tienda de San Isidro, por ser la tienda donde se inici? el plan piloto de implementaci?n de pantallas digitales llamados Kioscos, con el objetivo de proveer a los clientes una experiencia de autoservicio r?pida y eficiente. La implementaci?n de estas tecnolog?as responde a una de las estrategias de omnicanalidad que la firma ha incorporado dentro de sus objetivos corporativos, alineados a las nuevas formas de consumo de los usuarios, caracterizado por la hiperconectividad y la hiperinformaci?n que hoy caracteriza a los consumidores a nivel mundial

Study protocol; thyroid hormone replacement for untreated older adults with subclinical hypothyroidism - a randomised placebo controlled trial (TRUST)

Background: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Methods: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. Discussion: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Trial registration: Clinicaltrials.gov NCT01660126; registered 8th June 2012

Latitude drives diversification in M adagascar's endemic dry forest rodent E liurus myoxinus (subfamily N esomyinae)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100288/1/bij12143.pd

Models of turbulent dissipation regions in the diffuse interstellar medium

Supersonic turbulence is a large reservoir of suprathermal energy in the interstellar medium. Its dissipation, because it is intermittent in space and time, can deeply modify the chemistry of the gas. We further explore a hybrid method to compute the chemical and thermal evolution of a magnetized dissipative structure, under the energetic constraints provided by the observed properties of turbulence in the cold neutral medium. For the first time, we model a random line of sight by taking into account the relative duration of the bursts with respect to the thermal and chemical relaxation timescales of the gas. The key parameter is the turbulent rate of strain "a" due to the ambient turbulence. With the gas density, it controls the size of the dissipative structures, therefore the strength of the burst. For a large range of rates of strain and densities, the models of turbulent dissipation regions (TDR) reproduce the CH+ column densities observed in the diffuse medium and their correlation with highly excited H2. They do so without producing an excess of CH. As a natural consequence, they reproduce the abundance ratios of HCO+/OH and HCO+/H2O, and their dynamic range of about one order of magnitude observed in diffuse gas. Large C2H and CO abundances, also related to those of HCO+, are another outcome of the TDR models that compare well with observed values. The abundances and column densities computed for CN, HCN and HNC are one order of magnitude above PDR model predictions, although still significantly smaller than observed values

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012