Nutritional status and clinical outcome in elderly female surgical orthopaedic patients

The possible relationship between nutritional status and clinical outcome following orthopaedic hip surgery was investigated. The nutritional status of 60 elderly female patients admitted for elective total hip replacement (THR) and emergency fractured neck of femur surgery (FNF) was measured over time. Specific measures of clinical outcome, including well-being and functional status, were monitored during hospital stay and at 4, 8 and 26 weeks following discharge. Patients were allocated to a high nutritional risk group where any three of the following were less than the 5th percentile value: serum albumin, haemoglobin, triceps skinfold thickness, mid-upper arm muscle circumference and body weight. Using this definition, malnutrition was present in 4% of THR patients and 41% of FNF patients. It was found that the high risk patients had significantly longer convalescence periods, (median stay27.5 days compared with 0 days, P < 0.0009), and a greater proportion were dependent upon walking frames at 6 months (46% compared with 11%, P < 0.01). Fifty percent of the high risk patients had been living independently prior to admission, in contrast only 29% had returned to their homes at 6 months after discharge. The results indicate an apparent link between clinical outcome and nutritional status based upon the allocation procedure employed, which has the potential for ensuring cost-effective nutritional intervention.

Measuring the discrepancy between fecundity and lifetime reproductive success in a pollinating fig wasp

Lifetime reproductive success in female insects is often egg- or time-limited. For instance in pro-ovigenic species, when oviposition sites are abundant, females may quickly become devoid of eggs. Conversely, in the absence of suitable oviposition sites, females may die before laying all of their eggs. In pollinating fig wasps (Hymenoptera: Agaonidae), each species has an obligate mutualism with its host fig tree species [Ficus spp. (Moraceae)]. These pro-ovigenic wasps oviposit in individual ovaries within the inflorescences of monoecious Ficus (syconia, or ‘figs’), which contain many flowers. Each female flower can thus become a seed or be converted into a wasp gall. The mystery is that the wasps never oviposit in all fig ovaries, even when a fig contains enough wasp females with enough eggs to do so. The failure of all wasps to translate all of their eggs into offspring clearly contributes to mutualism persistence, but the underlying causal mechanisms are unclear. We found in an undescribed Brazilian Pegoscapus wasp population that the lifetime reproductive success of lone foundresses was relatively unaffected by constraints on oviposition. The number of offspring produced by lone foundresses experimentally introduced into receptive figs was generally lower than the numbers of eggs carried, despite the fact that the wasps were able to lay all or most of their eggs. Because we excluded any effects of intraspecific competitors and parasitic non-pollinating wasps, our data suggest that some pollinators produce few offspring because some of their eggs or larvae are unviable or are victims of plant defences.

The ecology of lizard reproductive output

Aim  We provide a new quantitative analysis of lizard reproductive ecology. Comparative studies of lizard reproduction to date have usually considered life-history components separately. Instead, we examine the rate of production (productivity hereafter) calculated as the total mass of offspring produced in a year. We test whether productivity is influenced by proxies of adult mortality rates such as insularity and fossorial habits, by measures of temperature such as environmental and body temperatures, mode of reproduction and activity times, and by environmental productivity and diet. We further examine whether low productivity is linked to high extinction risk. Location  World-wide. Methods  We assembled a database containing 551 lizard species, their phylogenetic relationships and multiple life history and ecological variables from the literature. We use phylogenetically informed statistical models to estimate the factors related to lizard productivity. Results  Some, but not all, predictions of metabolic and life-history theories are supported. When analysed separately, clutch size, relative clutch mass and brood frequency are poorly correlated with body mass, but their product – productivity – is well correlated with mass. The allometry of productivity scales similarly to metabolic rate, suggesting that a constant fraction of assimilated energy is allocated to production irrespective of body size. Island species were less productive than continental species. Mass-specific productivity was positively correlated with environmental temperature, but not with body temperature. Viviparous lizards were less productive than egg-laying species. Diet and primary productivity were not associated with productivity in any model. Other effects, including lower productivity of fossorial, nocturnal and active foraging species were confounded with phylogeny. Productivity was not lower in species at risk of extinction. Main conclusions  Our analyses show the value of focusing on the rate of annual biomass production (productivity), and generally supported associations between productivity and environmental temperature, factors that affect mortality and the number of broods a lizard can produce in a year, but not with measures of body temperature, environmental productivity or diet.

Reproductive technologies: the owned child and commodification

This article analyses some complexities in and around the idea that the child, in several recent discussions on reproductive technologies, is constantly brought in relation to the market and commodity, and yet is not simply equated with commodity. When and how is the child a commodity and not a commodity?

Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer

Duchenne muscular dystrophy is a fatal muscle-wasting disorder. Lack of dystrophin compromises the integrity of the sarcolemma and results in myofibers that are highly prone to contraction-induced injury. Recombinant adenoassociated virus (rAAV)-mediated dystrophin gene transfer strategies to muscle for the treatment of Duchenne muscular dystrophy (DMD) have been limited by the small cloning capacity of rAAV vectors and high titers necessary to achieve efficient systemic gene transfer. In this study, we assess the impact of codon optimization on microdystrophin (ΔAB/R3-R18/ΔCT) expression and function in the mdx mouse and compare the function of two different configurations of codon-optimized microdystrophin genes (ΔAB/R3-R18/ΔCT and ΔR4-R23/ΔCT) under the control of a muscle-restrictive promoter (Spc5-12). Codon optimization of microdystrophin significantly increases levels of microdystrophin mRNA and protein after intramuscular and systemic administration of plasmid DNA or rAAV2/8. Physiological assessment demonstrates that codon optimization of ΔAB/R3-R18/ΔCT results in significant improvement in specific force, but does not improve resistance to eccentric contractions compared with noncodon-optimized ΔAB/ R3-R18/ΔCT. However, codon-optimized microdystrophin ΔR4-R23/ΔCT completely restored specific force generation and provided substantial protection from contraction-induced injury. These results demonstrate that codon optimization of microdystrophin under the control of a muscle-specific promoter can significantly improve expression levels such that reduced titers of rAAV vectors will be required for efficient systemic administration.

Factors contributing to fecal incontinence in older people and outcome of routine management in home, hospital and nursing home settings

Objective: Fecal loading, cognitive impairment, loose stools, functional disability, comorbidity and anorectal incontinence are recognized as factors contributing to loss of fecal continence in older adults. The objective of this project was to assess the relative distribution of these factors in a variety of settings along with the outcome of usual management. Methods: One hundred and twenty adults aged 65 years and over with fecal incontinence recruited by convenience sampling from four different settings were studied. They were either living at home or in a nursing home or receiving care on an acute or rehabilitation elderly care ward. A structured questionnaire was used to elicit which factors associated with fecal incontinence were present from subjects who had given written informed consent or for whom assent for inclusion in the study had been obtained. Results: Fecal loading (Homes 6 [20%]; Acute care wards 17 [57%]; Rehabilitation wards 19 [63%]; Nursing homes 21 [70%]) and functional disability (Homes 5 [17%]; Acute care wards 25 [83%]; Rehabilitation wards 25 [83%]; Nursing homes 20 [67%]) were significantly more prevalent in the hospital and nursing home settings than in those living at home (P < 0.01). Loose stools were more prevalent in the hospital setting than in the other settings (Homes 11 [37%]; Acute care wards 20 [67%]; Rehabilitation wards 17 [57%]; Nursing homes 6 [20%]) (P < 0.01). Cognitive impairment was significantly more common in the nursing home than in the other settings (Nursing homes 26 [87%], Homes 5 [17%], Acute care wards 13 [43%], Rehabilitation wards 14 [47%]) (P < 0.01). Loose stools were the most prevalent factor present at baseline in 13 of the 19 (68%) subjects whose fecal incontinence had resolved at 3 months. Conclusion: The distribution of the factors contributing to fecal incontinence in older people living at home differs from those cared for in nursing home and hospital wards settings. These differences need to be borne in mind when assessing people in different settings. Management appears to result in a cure for those who are not significantly disabled with loose stools as a cause for their fecal incontinence, but this would need to be confirmed by further research.

Expected value, reward outcome, and temporal difference error representations in a probabilistic decision task

In probabilistic decision tasks, an expected value (EV) of a choice is calculated, and after the choice has been made, this can be updated based on a temporal difference (TD) prediction error between the EV and the reward magnitude (RM) obtained. The EV is measured as the probability of obtaining a reward x RM. To understand the contribution of different brain areas to these decision-making processes, functional magnetic resonance imaging activations related to EV versus RM (or outcome) were measured in a probabilistic decision task. Activations in the medial orbitofrontal cortex were correlated with both RM and with EV and confirmed in a conjunction analysis to extend toward the pregenual cingulate cortex. From these representations, TD reward prediction errors could be produced. Activations in areas that receive from the orbitofrontal cortex including the ventral striatum, midbrain, and inferior frontal gyrus were correlated with the TD error. Activations in the anterior insula were correlated negatively with EV, occurring when low reward outcomes were expected, and also with the uncertainty of the reward, implicating this region in basic and crucial decision-making parameters, low expected outcomes, and uncertainty.

Resistance to the anticoagulant rodenticides – the deployment of the new molecular methodology to identify mutations of the VKORC1 ‘resistance gene’, and understanding their potential impact on treatment outcome

Anticoagulants rodenticides have already known for over half a century, as effective and safe method of rodent control. However, discovered in 1958 anticoagulant resistance has given us a very important problem for their future long-term use. Laboratory tests provide the main method for identification the different types of anticoagulant resistances, quantify the magnitude of their effect and help us to choose the best pest control strategy. The main important tests are lethal feeding period (LFP) and blood clotting response (BCR) tests. These tests can now be used to quantify the likely effect of the resistance on treatment outcome by providing an estimate of the ‘resistance factor’. In 2004 the gene responsible for anticoagulant resistance (VKORC1) was identified and sequenced. As a result, a new molecular resistance testing methodology has been developed, and a number of resistance mutations, particularly in Norway rats and house mice. Three mutations of the VKORC1 gene in Norway rats have been identified to date that confer a degree of resistance to bromadiolone and difenacoum, sufficient to affect treatment outcome in the field.

Sublethal neonicotinoid insecticide exposure reduces solitary bee reproductive success

1. Pollinating insects provide crucial and economically important ecosystem services to crops and wild plants, but pollinators, particularly bees, are globally declining as a result of various driving factors, including the prevalent use of pesticides for crop protection. Sublethal pesticide exposure negatively impacts numerous pollinator lifehistory traits, but its influence on reproductive success remains largely unknown. Such information is pivotal, however, to our understanding of the long-term effects on population dynamics. 2 We investigated the influence of field-realistic trace residues of the routinely used neonicotinoid insecticides thiamethoxam and clothianidin in nectar substitutes on the entire life-time fitness performance of the red mason bee Osmia bicornis. 3 We show that chronic, dietary neonicotinoid exposure has severe detrimental effects on solitary bee reproductive output. Neonicotinoids did not affect adult bee mortality; however, monitoring of fully controlled experimental populations revealed that sublethal exposure resulted in almost 50% reduced total offspring production and a significantly male-biased offspring sex ratio. 4 Our data add to the accumulating evidence indicating that sublethal neonicotinoid effects on non-Apis pollinators are expressed most strongly in a rather complex, fitness-related context. Consequently, to fully mitigate long-term impacts on pollinator population dynamics, present pesticide risk assessments need to be expanded to include whole life-cycle fitness estimates, as demonstrated in the present study using O. bicornis as a model.

Data-driven treatment selection for seamless phase II/III trials incorporating early-outcome data

Seamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods.

Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats

Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

Biology and reproductive behavior of Murgantia histrionica (Heteroptera: Pentatomidae)

Life history parameters and reproductive behaviors of the harlequin bug, Murgantia histrionica Hahn (Heteroptera: Pentatomidae), were determined. Total developmental time from egg to adult was ≈48 d. After a sexual maturation period of ≈7 d, both sexes mated repeatedly, with females laying multiple egg masses of 12 eggs at intervals of 3 d. Adult females lived an average of 41 d, whereas adult males lived an average of 25 d. Courtship and copulation activities peaked in the middle of the photophase. In mating experiments in which mixed sex pairs of virgin and previously mated bugs were combined in all possible combinations, the durations of courtship and copulation by virgin males were significantly longer with both virgin and previously mated females than the same behaviors for previously mated males. When given a choice between a virgin or previously mated female, previously mated males preferred to mate with virgin females, whereas virgin males showed no preference for virgin over previously mated females. Analyses of mating behaviors with ethograms and behavioral transition matrices suggested that a primary reason for failure to copulate by virgin males was the incorrect rotation of their pygophores to the copulation position, so that successful alignment of the genitalia could not occur.