An important 2′-OH group for an RNA–protein interaction

We have investigated the role of 2′-OH groups in the specific interaction between the acceptor stem of Escherichia coli tRNACys and cysteine-tRNA synthetase. This interaction provides for the high aminoacylation specificity observed for cysteine-tRNA synthetase. A synthetic RNA microhelix that recapitulates the sequence of the acceptor stem was used as a substrate and variants containing systematic replacement of the 2′-OH by 2′-deoxy or 2′-O-methyl groups were tested. Except for position U73, all substitutions had little effect on aminoacylation. Interestingly, the deoxy substitution at position U73 had no effect on aminoacylation, but the 2′-O-methyl substitution decreased aminoacylation by 10-fold and addition of the even bulkier 2′-O-propyl group decreased aminoacylation by another 2-fold. The lack of an effect by the deoxy substitution suggests that the hydrogen bonding potential of the 2′-OH at position U73 is unimportant for aminoacylation. The decrease in activity upon alkyl substitution suggests that the 2′-OH group instead provides a monitor of the steric environment during the RNA–synthetase interaction. The steric role was confirmed in the context of a reconstituted tRNA and is consistent with the observation that the U73 base is the single most important determinant for aminoacylation and therefore is a site that is likely to be in close contact with cysteine-tRNA synthetase. A steric role is supported by an NMR-based structural model of the acceptor stem, together with biochemical studies of a closely related microhelix. This role suggests that the U73 binding site for cysteine-tRNA synthetase is sterically optimized to accommodate a 2′-OH group in the backbone, but that the hydroxyl group itself is not involved in specific hydrogen bonding interactions.

Hormone replacement therapy and everyday memory in mid-aged New Zealand women

While empirical research to date has generally supported positive effects of estrogen on verbal memory performance in women, the literature examining specific effects of Hormone Replacement Therapy (HRT) on cognitive functioning in mid-life women is more equivocal. The Rivermead Behavioural Memory Test-Extended Version (RBMT-E), a measure of everyday memory functioning in adults within an average range of cognitive functioning, was administered to a sample of 104 New Zealand women aged 40 to 60 years who had self-selected to either use or not use HRT (53 HRT users and 51 non-users). Self-report. measures of mood, stress, general health and menopausal symptoms were also administered. These variables, along with age and education level, were used in analyses of group differences on the everyday memory measures. Results showed significant differences between the groups for three sub-tests of the RBMT-E:'Story Immediate', 'Story Delayed', and 'Message Delayed'. Women who use HRT scored higher on these subtests than those who do not use HRT. After calculation of a total profile score (adjusting for age and IQ), HRT users score higher than HRT non-users on the RBMT-E overall measure of Everyday Memory. These pilot results suggest that HRT use in this sample-is related to enhanced verbal memory in everyday memory tasks and that the RBMT-E may be a useful tool for further work in this area of research.

Low-bandwidth telerehabilitation for patients who have undergone total knee replacement: preliminary results

We have developed a low-bandwidth, Internet-based telerehabilitation system to provide outpatient rehabilitation to patients who have undergone total knee arthroplasty. The preliminary efficacy of this treatment programme in terms of both physical and functional objective outcome measures was assessed on 21 patients. Subjects receiving a six-week rehabilitation programme were randomized to the telerehabilitation system or the usual face-to-face method. The physical and functional improvements in the telerehabilitation group were similar to those in the control group. There was a non-significant trend for greater improvements in the telerehabilitation group for most outcome measurements. The telerehabilitation programme was well received by patients. The results of this study provide evidence for the efficacy of low-bandwidth telerehabilitation consultations.

The effect of hormone replacement therapy on mood and everyday memory in younger mid-life women

Research on the effect of hormone replacement therapy (HRT) on both mood and memory indicates that oestrogen may enhance verbal memory in younger mid-aged women. This study examined the effect of HRT on everyday memory, while accounting for mood changes, in women between ages 40 and 60. A within-subjects comparison of 17 women, showed that mood, everyday memory, working memory, and delayed verbal memory improved after 3 months of HRT use. The improvement in memory was not mediated by mood, but changes in mood were moderated by exercise habits. The results suggest that verbal memory in particular may be enhanced by HRT in this age group, and everyday memory is an important construct to consider in future research.

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.

The sedimentology and diagenesis of the Pendleside limestone group in the Craven Basin of Northern England. Available in 2 volumes.

This thesis describes the stratigraphy, sedimentology and diagenesis of the Pendleside Limestone (Asbian age), a sequence of limestones, shales and dolostones in the Clitheroe area of N. W. England. Field study of 19 measured sections indicates that it was deposited in a rhythmically subsiding basin (Craven Basin) because of movements on the Mid-Craven Fault which was active in Dinantian times. The sequence is up to 190m thick and consists mostly of distal turbidite deposits which have been reworked at horizons when sediment accumulation built up to the wave base. The original depositional fabric and mineralogy of the Pendleside Limestone Group has been extensively modified by diagenetic processes including cementation, authi­genesis, dolomitization and silicification. These processes have been studied using a wide variety of laboratory techniques. The carbonate cements of the PendIeside Limestone consist predominantly of ferroan calcite and non-ferroan calcite with microdolomite incIusions. The former is probably a stable replacement of original-high-magnesian calcite. Cementation was accompanied by the formation of authigenic albite and quartz. Much of the upper part of the Pendleside Limestone has been extensively dolomitized and chertified. Several distinct zones of dolomitization are found which increase in thickness and intensity towards the top of the Pendleside Limestone Group. The dolostone horizons correspond to coarser-grained lithologies deposited during periods of shallow water sedimentation. The composition of the dolomites changes from ferroan dolomite in the lower part of the Group to non-ferroan dolomite in the upper part. The low strontium and sodium content of the dolostones in association with the other evidence suggests that the dolomitization was brought about in an open system by the mixing of marine and fresh water in phreatic lens which were established at periodic intervals. The dolomitization was closely associated with chertification although this was initiated by the dissolution of siliceous spicules which provided the necessary source of silica.

Diagenesis and aquifer characteristics of the Sherwood Sandstone Group in North Nottinghamshire

The Sherwood Sandstone Group forms an important aquifer in Eastern England, which in North Nottinghamshire comprises the Nottingham Castle and Lenton Sandstone Formations. The aquifer is formed by an alluvial red-bed sequence dominated by medium-coarse grained sandstones which are texturally immature to submature and have only been subjected to shallow burial diagenesis. These sandstones reached the mature stage of the meso diagenetic regime, and four stages are recognized in their diagenetic history depending upon the physical/chemical processes prevailing and the subsequent effect on porosity and permeability. Stage "One" represents changes including dissolution of unstable silicates, clay replacement, red colouration and precipitation of authigenic minerals (quartz, feldspar, illite, l/S, kaolinite, dolomite, ferroan calcite, calcite). The net result of these changes was porosity reduction. Stage "Two" included changes due to mechanical compaction which resulted in minor porosity reduction. Stage "Three" was the main phase of secondary porosity enhancement. Stage "Four" represents changes taking place in the present groundwater where porosity and permeability may have been increased by dissolution and partly reduced by kaolinite precipitation. Porosity measured by water-resaturation and Hg-injection gave average values of 25.63% and 24.85% respectively. The results are comparable and showed marked correlation especially in highly porous/permeable rocks. Porosity measurements from photomicrographs were markedly offset from laboratory results. Horizontal Kw ranged between 1.43 x 10-5 and 1.13 x 10-1 mm/sec, with an average of  1.68 x 10-2 mm/sec. The estimated KHg ranged between 7.29 x 10-6 and 6.99 x 10-2 mm/sec with an average of 1.47 x 10-2 mm/sec. Both results are significantly correlated for highly porous/permeable rocks. The hydraulic properties are highly dependent upon the diagenetic properties (as most of the pores present are of secondary origin) as well as the pore size distribution. The chemistry of these groundwaters indicates that they are under-saturated with respect to dolomite, calcite, K-feldspar, l/S clay, and montmorillonite. The precipitation of kaolinite,and to a lesser extent illite, is favoured in the present groundwater regime.

Recent research trend of economic-lot scheduling problems

Purpose - This research note aims to present a summary of research concerning economic-lot scheduling problem (ELSP). Design/methodology/approach - The paper's approach is to review over 100 selected studies published in the last 15 years (1997-2012), which are then grouped under different research themes. Findings - Five research themes are identified and insights for future studies are reported at the end of this paper. Research limitations/implications - The motivation of preparing this research note is to summarize key research studies in this field since 1997, when the ELSP problems have been verified as NP-hard. Originality/value - ELSP is an important scheduling problem that has been studied since the 1950s. Because of its complexity in delivering a feasible analytical closed form solution, many studies in the last two decades employed heuristic algorithms in order to come up with good and acceptable solutions. As a consequence, the solution approaches are quite diversified. The major contribution of this paper is to provide researchers who are interested in this area with a quick reference guide on the reviewed studies. © Emerald Group Publishing Limited.

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

A Group-Enhanced Sprint Interval Training Program for Amateur Athletes

Sprint interval training (SIT) can elicit improvements in aerobic and anaerobic capacity. While variations in SIT protocols have been investigated, the influence of social processes cannot be overlooked. As research supports the use of groups to influence individual cognitions and behaviours, the current project assessed the effectiveness of a group-based intervention with participants conducting SIT. Specifically, 53 amateur athletes (age, 21.9 ± 2.9 years; 53% females) took part in a 4-week training program (3 sessions per week, 30-s “all-out” efforts with 4 min active recovery, repeated 4–6 times per session), and were assigned to “true group”, aggregate, or individual conditions. Results indicated no significant differences between groups for the physiological measures. With regards to training improvements from baseline for all participants— regardless of condition — significant main effects for time were identified for maximal oxygen uptake (2.5–2.8 mL·kg−1·min−1, p < 0.001, η2 = 0.03), time-trial performance (14–32 s, p < 0.001, η2 = 0.37), and anaerobic power (1.1–1.7 k·h−1, p < 0.001, η2 = 0.66). With regards to the psychological measures, significant main effects between groups were found for motivation (p = 0.033, η2 = 0.13), task self-efficacy (p = 0.018, η2 = 0.15), and scheduling self-efficacy (p = 0.003, η2 = 0.22). The true group experienced greater improvements in motivation than the individual condition, but the aggregate and individual conditions demonstrated greater increases in task and scheduling self-efficacy. Though the SIT paradigm employed induced training improvements similar to previous work, the group intervention was not able to further these improvements

Shift Scheduling in Services When Employees Have Limited Availability: An L. P. Approach

This paper compares two linear programming (LP) models for shift scheduling in services where homogeneously-skilled employees are available at limited times. Although both models are based on set covering approaches, one explicitly matches employees to shifts, while the other imposes this matching implicitly. Each model is used in three forms—one with complete, another with very limited meal break placement flexibility, and a third without meal breaks—to provide initial schedules to a completion/improvement heuristic. The term completion/improvement heuristic is used to describe a construction/ improvement heuristic operating on a starting schedule. On 80 test problems varying widely in scheduling flexibility, employee staffing requirements, and employee availability characteristics, all six LP-based procedures generated lower cost schedules than a comparison from-scratch construction/improvement heuristic. This heuristic, which perpetually maintains an explicit matching of employees to shifts, consists of three phases which add, drop, and modify shifts. In terms of schedule cost, schedule generation time, and model size, the procedures based on the implicit model performed better, as a group, than those based on the explicit model. The LP model with complete break placement flexibility and implicitly matching employees to shifts generated schedules costing 6.7% less than those developed by the from-scratch heuristic.

Effectiveness and Cost-effectiveness of Outpatient Physiotherapy After Knee Replacement for Osteoarthritis: Study Protocol for a Randomised Controlled Trial

Background: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement. Methods/design: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over 6 weeks and will involve task-orientated and individualised exercises. The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective. Discussion: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients’ outcomes and improved health care resource efficiency.