Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Lighting the fuse: Cultivating the masculine physics habitus – a case study of Victor aged 10-18

This chapter presents a longitudinal case study analysis of Victor, a young man who was interviewed from the ages of 10–19, together with his mother, Sam, and who went on to study for a degree in astrophysics. We apply a Bourdieusian conceptual lens to the data, to explore how interactions of capital, habitus and field combine to possibilise Victor and his trajectory to being/becoming a physicist. We also identify specific alignments of his habitus and capital with dominant notions of masculinity and ‘cleverness’ that are demanded and normalised within physics and which, we argue, are key to the reproduction of the elite nature of physics

Obesity and pronated foot type may increase the risk of chronic plantar heel pain : a matched case-control study

Background : Chronic plantar heel pain (CPHP) is one of the most common musculoskeletal disorders of the foot, yet its aetiology is poorly understood. The purpose of this study was to examine the association between CPHP and a number of commonly hypothesised causative factors.Methods : Eighty participants with CPHP (33 males, 47 females, mean age 52.3 years, S.D. 11.7) were matched by age (&plusmn; 2 years) and sex to 80 control participants (33 males, 47 females, mean age 51.9 years, S.D. 11.8). The two groups were then compared on body mass index (BMI), foot posture as measured by the Foot Posture Index (FPI), ankle dorsiflexion range of motion (ROM) as measured by the Dorsiflexion Lunge Test, occupational lower limb stress using the Occupational Rating Scale and calf endurance using the Standing Heel Rise Test.Results : Univariate analysis demonstrated that the CPHP group had significantly greater BMI (29.8 &plusmn; 5.4 kg/m2 vs. 27.5 &plusmn; 4.9 kg/m2; P &lt; 0.01), a more pronated foot posture (FPI score 2.4 &plusmn; 3.3 vs. 1.1 &plusmn; 2.3; P &lt; 0.01) and greater ankle dorsiflexion ROM (45.1 &plusmn; 7.1&deg; vs. 40.5 &plusmn; 6.6&deg;; P &lt; 0.01) than the control group. No difference was identified between the groups for calf endurance or time spent sitting, standing, walking on uneven ground, squatting, climbing or lifting. Multivariate logistic regression revealed that those with CPHP were more likely to be obese (BMI &ge; 30 kg/m2) (OR 2.9, 95% CI 1.4 &ndash; 6.1, P &lt; 0.01) and to have a pronated foot posture (FPI &ge; 4) (OR 3.7, 95% CI 1.6 &ndash; 8.7, P &lt; 0.01).Conclusion : Obesity and pronated foot posture are associated with CPHP and may be risk factors for the development of the condition. Decreased ankle dorsiflexion, calf endurance and occupational lower limb stress may not play a role in CPHP.<br /

Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

Plantar calcaneal spurs in older people: longitudinal traction or vertical compression?

<p>Abstract</p> <p>Background</p> <p>Plantar calcaneal spurs are common, however their pathophysiology is poorly understood. This study aimed to evaluate the prevalence and correlates of plantar calcaneal spurs in a large sample of older people.</p> <p>Methods</p> <p>Weightbearing lateral foot radiographs of 216 people (140 women and 76 men) aged 62 to 94 years (mean age 75.9, <smcaps>SD</smcaps> 6.6) were examined for plantar calcaneal and Achilles tendon spurs. Associations between the presence of spurs and sex, body mass index, radiographic measures of foot posture, self-reported co-morbidities and current or previous heel pain were then explored.</p> <p>Results</p> <p>Of the 216 participants, 119 (55%) had at least one plantar calcaneal spur and 103 (48%) had at least one Achilles tendon spur. Those with plantar calcaneal spurs were more likely to have Achilles tendon spurs (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2 to 3.5). Prevalence of spurs did not differ according to sex. Participants with plantar calcaneal spurs were more likely to be obese (OR = 7.9, 95% CI 3.6 to 17.0), report osteoarthritis (OR = 2.6, 95% CI 1.6 to 4.8) and have current or previous heel pain (OR = 4.6, 95% CI 2.3 to 9.4). No relationship was found between the presence of calcaneal spurs and radiographic measures of foot posture.</p> <p>Conclusion</p> <p>Calcaneal spurs are common in older men and women and are related to obesity, osteoarthritis and current or previous heel pain, but are unrelated to radiographic measurements of foot posture. These findings support the theory that plantar calcaneal spurs may be an adaptive response to vertical compression of the heel rather than longitudinal traction at the calcaneal enthesis.</p

Minority ethnic students and science participation: a qualitative mapping of achievement, aspiration, interest and capital

In the UK, the ‘leaky pipeline’ metaphor has been used to describe the relationship between ethnicity and science participation. Fewer minority ethnic students continue with science in post-compulsory education, and little is known about the ways in which they participate and identify with science, particularly in the secondary school context. Drawing on an exploratory study of 46 interviews and 22 h of classroom observations with British students (aged 11–14) from Black Caribbean, Bangladeshi, Pakistani, Indian and Chinese ethnic backgrounds, this paper identified five ‘types’ of science participation among minority ethnic students. The five types of science participation emerged from an analysis of students’ science achievement, science aspiration, science interest and science capital. The characteristics of the five types are as follows: Science adverse students have no aspirations towards science and lacked interest, achievement and capital in science. Science intrinsic students have high science aspirations, interest and capital but low science attainment. Students who are science intermediate have some aspirations, interest and capital in science, with average science grades. Science extrinsic students achieve highly in science, have some science capital but lacked science aspirations and/or interest. Science prominent students are high science achievers with science aspirations, high levels of interest and capital in science. The findings highlight that minority ethnic students participate in science in diverse ways. Policy implications are suggested for each type as this paper provides empirical evidence to counter against public (and even some academic) discourses of minority ethnic students as a homogeneous group

Inhibition of PIKfyve by YM-201636 Dysregulates Autophagy and Leads to Apoptosis-Independent Neuronal Cell Death

The lipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P-2), synthesised by PIKfyve, regulates a number of intracellular membrane trafficking pathways. Genetic alteration of the PIKfyve complex, leading to even a mild reduction in PtdIns(3,5)P-2 results in marked neurodegeneration via an uncharacterised mechanism. In the present study we have shown that selectively inhibiting PIKfyve activity, using YM-201636, significantly reduces the survival of primary mouse hippocampal neurons in culture. YM-201636 treatment promoted vacuolation of endolysosomal membranes followed by apoptosis-independent cell death. Many vacuoles contained intravacuolar membranes and inclusions reminiscent of autolysosomes. Accordingly, YM-201636 treatment increased the level of the autophagosomal marker protein LC3-II, an effect that was potentiated by inhibition of lysosomal proteases, suggesting that alterations in autophagy could be a contributing factor to neuronal cell death

Quantitative Historical Change in Bumblebee (Bombus spp.) Assemblages of Red Clover Fields

Flower visiting insects provide a vitally important pollination service for many crops and wild plants. Recent decline of pollinating insects due to anthropogenic modification of habitats and climate, in particular from 1950's onwards, is a major and widespread concern. However, few studies document the extent of declines in species diversity, and no studies have previously quantified local abundance declines. We here make a quantitative assessment of recent historical changes in bumblebee assemblages by comparing contemporary and historical survey data. species observed in the 1930's, five species were not observed at present. The latter were all long-tongued, late-emerging species.Because bumblebees are important pollinators, historical changes in local bumblebee assemblages are expected to severely affect plant reproduction, in particular long-tubed species, which are pollinated by long-tongued bumblebees

Factors affecting health-related quality of life in Thai children with thalassemia

<p>Abstract</p> <p>Background</p> <p>Knowledge of the factors associated with health-related quality of life (HRQOL) among patients with thalassemia is essential in developing more suitable clinical, counseling, and social support programs to improve treatment outcomes of these patients. In light of the limited research in this area, this study aims to examine factors associated with HRQOL among children and adolescents with thalassemia in Thailand.</p> <p>Methods</p> <p>A cross-sectional survey was conducted in three selected hospitals in Thailand during June to November 2006. PedsQL™ 4.0 Generic Core Scale (Thai version) was used to assess HRQOL in 315 thalassemia patients between 5 and 18 years of age. Other related clinical characteristics of the patients were collected via medical record review.</p> <p>Results</p> <p>The mean (SD) of the total summary score was 76.67 (11.40), while the means (SD) for the Physical Health Summary score and Psychosocial Health Summary score were 78.24 (14.77) and 75.54 (12.76), respectively. The school functioning subscale scored the lowest, with a mean of 67.89 (SD = 15.92). The following factors significantly affected the HRQOL of the patients: age; age at onset of anemia and age at first transfusion; pre-transfusion hemoglobin (Hb) level; receiving a blood transfusion during the previous three months; and disease severity. In addition, iron chelation therapy had a significant negative effect on HRQOL in the school functioning subscale. In contrast, serum ferritin level, frequency of blood transfusions per year, and gender were not significantly related to HRQOL among these patients. The results from multivariate analysis also confirmed these findings.</p> <p>Conclusions</p> <p>To improve HRQOL of thalassemia patients, suitable programs aimed at providing psychosocial support and a link between the patient, school officials, the family and the physician are important, especially in terms of improving the school functioning score. The findings also confirmed the importance of maintaining a pre-transfusion Hb level of at least 9-10.5 g/dL. In addition, special care and attention should be given to patients with a severe condition, and those who are receiving subcutaneous iron chelation therapy.</p