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IntroductionSarcopenia is a progressive loss in muscle mass, strength and function, the adverse consequences of which are severe, affecting quality of life and placing an increasing burden on social and healthcare systems. Vitamin D status is known to be associated with markers of sarcopenia, namely muscle mass, strength and function. Also, resistance exercise training (RET) is currently the only proven intervention to treat sarcopenia. However, very little data exist on the influence of combining the two interventions of vitamin D supplementation and resistance exercise training, although a recent systematic review provides tentative support for the current study’s hypothesis that the combined intervention may further improve musculoskeletal function above exercise training alone. The aim of the present study is to determine whether vitamin D3supplementation is any more effective in improving musculoskeletal function when combined with RET compared with exercise training alone in older adults.Methods and analysisThis double-blinded randomised placebo-controlled trial will recruit a target of 127 eligible men and women aged ≥65 years living independently or in sheltered housing within the Birmingham area to two groups: (1) 6 months RET and placebo or (2) 6 months RET and 800 IU/d vitamin D3. Measures of muscle power (Nottingham Power Rig), body composition (dual energy X-ray absorptiometry), muscle function (short physical performance battery, timed up and go), falls and fractures as events will be assessed. Assessments will take place at baseline and postintervention, with intermittent monitoring of bone turnover, calcium and vitamin D. The primary outcome will be lower limb extensor power output. Analyses of within-group changes and between-group differences in outcome measures are planned.Ethics and disseminationThe EXVITD study has ethical approval granted by the Black Country National Health Service Research Ethics Committee (14/WM/1220). Results of this trial will be submitted for publication in peer-reviewed journals and presented at conferences. The study is being conducted according to the principles of the Declaration of Helsinki.Trial registration numberNCT02467153; Post-results.

The increasing prevalence of low pI non-mAb therapeutics as well as current challenges in mAb-aggregate separations and low recoveries motivate further development in the multimodal anion exchange (MM AEX) space. In this work, linear salt gradient experiments at pH 7 were used to evaluate the retention of model proteins (with pI from 3.4 to 6.8) in 17 novel MM AEX prototype systems. The ligands were organized into three series. Series 1 extended previous work in multimodal ligand design and included a hydroxyl variant and linker length variants. Series 2 and 3 investigated the nature of hydrophobicity in MM AEX systems by adding hydrophobic (series 2) or fluorine (series 3) substituents to a solvent exposed phenyl ring. Compared to the commercial resin Capto Adhere, the series 1 and 3 ligands exhibited weaker binding, while some of the series 2 aliphatic prototypes showed dramatically increased retention and unique selectivities. Within series 1, the model proteins eluted earlier in the gradient as the charge-hydrophobic group distance on the ligand was increased from 4.9 A to 8.5 A. For the aliphatic variants in series 2, proteins that eluted early in the salt gradient were not affected by the increase in ligand hydrophobicity, while the later eluting proteins bound stronger as the length of the aliphatic substituent increased. The series 3 variants indicated that phenyl ring fluorination created subtle changes in protein elution in these MM AEX systems. Retention data from the three series was used to generate a partial least squares QSAR model based on both protein and ligand descriptors which accurately predicted protein retention with a training R 2 of 0.81 and a test R 2 of 0.76. The retention characteristics of some prototypes such as the earlier elution and unique selectivities compared to Capto Adhere suggest that they could potentially provide unique selectivities and increased recovery for the downstream processing of both mAb and non-mAb biotherapeutics.

The present paper builds upon previous work on mAb domain contributions to multimodal (MM) chromatography by examining how pH can impact mAb surface properties and retention in these systems. Linear salt gradient experiments were carried out between pH 5-7 for several mAbs with different pI and surface hydrophobicities in four different MM CEX resins at two ligand densities. mAb retention showed an inverse, non-linear correlation with pH. Changing pH affected the elution order, creating unique windows of selectivity in each of the MM CEX resins. One mAb showed a pH-dependent spectrum of domain contributions, demonstrating that pH can be used to tune the relative importance of the (Fab)2 and Fc domains for some mAbs in MM systems. Positive, negative, and hydrophobic patches were calculated between pH 5-7 for the mAbs. Visualizing these patches on the protein surface demonstrated that each mAb showed a unique distribution of surface charge and hydrophobicity that changed with pH. The sum of patch areas was tracked across this pH range to quantitatively understand how pH impacted these important surface properties. The quantitative analysis then was narrowed to consider only patches in the CDR loops, which were hypothesized to be an important interaction site for some mAbs in these systems. Interestingly, differences in the titration of CDR loop patches for each mAb were shown to be a result of Histidine titrations and patches in this region were qualitatively correlated with experimental trends including the observed elution order reversals. These results indicate that pH potentially can be employed as a lever for the strategic design of multimodal steps to create flow through, bind and elute, or weak partitioning operations with important implications for the design of integrated and/or continuous downstream purification processes. Furthermore, the ability to tune domain contributions in MM separations using pH creates intriguing possibilities for current downstream challenges such as the removal of product-related impurities, as well as the purification of bispecific mAbs.

The recovery potential of endangered species is limited by the high prevalence of human-modified habitats, while effective in situ conservation strategies to identify and restore disturbed habitat within species ranges are lacking. Our goal was to determine the impact of human disturbance on the endangered endemic Barrens willow (Salix jejuna) to provide science-based protocols for future restoration of disturbed habitats; a key component of conservation and recovery plans for many rare plant species. Our study examined differences in substrate (e.g., % total plant cover, % species cover, substrate type) and vegetation in naturally- (via frost activity) vs human-disturbed limestone barrens (Newfoundland, Canada), across the entire species range of the endangered Barrens willow. There were distinct differences in substrate conditions and vegetation community structure between naturally- and human-disturbed limestone barrens habitat throughout the narrow range of this endemic willow. Human-disturbed sites are more homogeneous and differ significantly from the naturally-disturbed sites having a much coarser substrate (30% more gravel) with less fine grained sands, less exposed bedrock, decreased soil moisture, increased nitrogen content, and reduced phosphorus content. Substrate differences can inhibit return to the natural freeze-thaw disturbance regime of the limestone barrens, negatively affecting long-term persistence of this, and other rare plants. The structure of associated vegetation (specifically woody species presence) negatively affected willow abundance but was not linked to disturbance type. Human-disturbed sites are potential candidates for endangered plant recovery habitat if natural ecosystem processes, vegetation community structure, and habitat heterogeneity are restored, thereby supporting the establishment of long term viable populations.

A developmentally normal adolescent boy with a history of childhood absence epilepsy presented with recurrence of pyknolepsy after a seven-year period of remission. The characteristics of his EEG showed the same 3-Hz generalised spike-wave discharge as in his previous EEG in childhood. To our knowledge, this is the first case report describing recurrence of childhood absence epilepsy as pyknolepsy in an adolescent. [Published with video sequences].

Cognitive impairment is prevalent among cancer patients receiving palliative care. It affects both clinical management and research with these patients. Cognitive impairments can often be reversed by appropriate therapeutic intervention, but many cases of cognitive impairment among palliative care patients will remain undetected by clinical staff unless formal assessment is conducted. Selection of an appropriate method of assessment should be guided by the goal for which assessment is undertaken, the ways in which the special characteristics of palliative care patients constrain the gathering of information, the type of information and the scale of measurement required, the validity, reliability and standardisation of the tests available, and the significance attached to test outcomes.A wide variety of methods for assessing cognitive competence is available. They differ in the type of information provided, the scale of measurement, and the breadth of the skills assessed. Each is most suitable for ...

Studies have suggested that engagement in a programme of exercise is beneficial for people living with Multiple Scelrosis (MS). There is evidence of improvements in mobility, overall health and the management of some symptoms such as fatigue, muscle stiffness, anxiety and depression. St Giles Hospice has been working to develop it’s provision of Supportive Care, working with community partners to meet the needs of those affected by a life limiting illness who have previously not easily accessed hospice services. A 12 week pilot exercise and support programme was undertaken working in collaboration with a community based exercise facilitator, and local NHS MS services. The aims: promote and maintain independence improve muscle strength, flexibility, mobility and activity provide a supportive environment introduce patients to hospice support The exercise class was set to music, using a range of equipment, most participants began from a seated position, with encouragement to stand if appropriate, there was focus on improving strength, stamina, mobility, co-ordination, balance, flexibility and confidence The outcomes 9 people attended, aged between 43 and 77 Overall attendance = 75%, 83 out of 111 possible attendances Evaluation: participants recorded sit to stand from their chair as a measure of leg strength at the beginning and end of the course. The results showed significant improvement in all participants demonstrating a tangible increase in leg strength and technique. Being able to quantify their own progress boosted self-esteem, Participants reported significant social and supportive benefits to attending. The hospice has engaged in dialogue with commissioners to support this work. We have engaged with other MS patients, their carers and NHS staff to promote the benefits of the programme. We have engaged in dialogue with the patients who have attended and work with them to provide a maintenance programme.

A mouse model for cyclophosphamideinduced testicular damage has been created which produces severe damage to both spermatogonia and maturing spermatocytes. Pretreatment and continued administration of [D-leu 6 ]-des-Gly-NH 2 10 pro-ethylamide GnRH, a synthetic analogue of gonadotropin-releasing hormone, produces striking protection from the histologically detectable cyclophosphamide-induced damage. These results suggest that temporary interruption of the pituitarygonadal axis may ameliorate the gonadal toxicity of systemic chemotherapy.

La Loi sur la protection de la langue inuit (LPLI) est une loi récente du Nunavut. Unique en son genre au Canada, elle est plus ambitieuse encore que la Charte de la langue française du Québec. Loi controversée, certains se demandent si le législateur n’aurait pas outrepassé ses pouvoirs en adoptant certaines de ses dispositions. En effet, l’article 3 de la LPLI prétend obliger les ministères, organismes ou institutions du gouvernement fédéral opérant au Nunavut à fournir leurs services destinés au public et à afficher leurs panneaux en langue inuit, alors même que ces organisations agissent à l’intérieur d’un champ de compétence fédérale. Les articles 29, 30 et 34 de la LPLI rendent obligatoire la préparation d’un plan d’action pour la langue inuit précisant la manière dont une organisation entend respecter la loi. Ce plan doit être approuvé par le commissaire aux langues, qui dispose d’un important pouvoir d’enquête relativement au respect de la loi. Au premier abord, ces dispositions semblent contredire la règle aujourd’hui acceptée selon laquelle un ordre de gouvernement peut légiférer en matière de langue dans la mesure où il le fait de manière accessoire à un champ de compétence qui lui est propre. Cette norme tire sa force de certaines particularités de la Loi constitutionnelle de 1867. Toutefois, après analyse, il appert que ce cadre conceptuel ne s’applique pas au Nunavut. Ce dernier détient bel et bien le pouvoir d’imposer sur son territoire l’utilisation de la langue inuit aux ministères, organismes et institutions du gouvernement fédéral., The Inuit Language Protection Act (ILPA) is a recent Nunavut statute. The only one of its kind in Canada, it is even more ambitious than Quebec’s Charter of the French Language. A controversial statute, some question whether the legislator has exceeded its competence in adopting certain of its provisions. Indeed, section 3 of the ILPA aims to require federal departments, agencies, or institutions operating in Nunavut to provide public services and to display signs in the Inuit language, even when these organizations are acting within an area of federal legislative competence. Sections 29, 30, and 34 of the ILPA provide for the mandatory preparation of an Inuit Language Plan, detailing how an organization will comply with the legislation. The languages commissioner, who possesses broad powers of investigation in order to ensure compliance with the legislation, must approve this plan. At first glance, these sections seem to contradict the established rule that a government can legislate with respect to language provided that this legislation is ancillary to its own areas of competence. This rule derives from certain particularities of the Constitution Act, 1867. However, further analysis leads to the conclusion that this conceptual framework does not apply to Nunavut. The latter holds the power to require, on its territory, the use of the Inuit language by federal departments, agencies, and institutions.