Pain in traumatic upper limb amputees in Sierra Leone.

Data on 40 upper limb amputees (11 bilateral) with regard to stump pain, phantom sensation and phantom pain is presented. All the patients lost their limbs as a result of violent injuries intended to terrorise the population and were assessed 10-48 months after the injury. All amputees reported stump pain in the month prior to interview and ten of the 11 bilateral amputees had bilateral pain. Phantom sensation was common (92.5%), but phantom pain was only present in 32.5% of amputees. Problems in translation and explanation may have influenced the low incidence of phantom pain and high incidence of stump pain. In the bilateral amputees phantom sensation, phantom pain and telescoping all showed bilateral concordance, whereas stump pain and neuromas did not show concordance. About half the subjects (56%) had lost their limb at the time of injury (primary) while the remainder had an injury, then a subsequent amputation in hospital (secondary). There was no association between the incidence of phantom pain and amputation irrespective of being primary or secondary

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo.

Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oestrogen and progesterone on cellular proliferation can be replicated in locally advanced cervical cancer in vivo and whether these effects, if any, are related to oestrogen and progesterone receptor (ER and PgR) content of the tumour. One hundred post-menopausal patients with locally advanced cervical cancer were systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 micrograms: (3) norethisterone 5 mg: (4) a combination of ethinyl oestradiol and norethisterone. Hormone treatment (five doses) was given orally every 12 h. Tissue biopsies were taken before and 12 h after the last hormone treatment. S-phase fraction (SpF) was measured by flow cytometry, and ER and PgR were measured by enzyme immunoassay. Results were analysed using two-factor analysis of variance, the factors being oestrogen-absent or present- and progesterone-absent or present. The main effects of oestrogen were increases in SpF, ER and PgR, which were statistically significant (P = 0.0056, 0.0009 and 0.01 respectively), indicating that there is much greater change in these three parameters in the presence of oestrogen (mean changes 7.808%, 6.258 fmol mg-1 and 12.716 fmol mg-1 for SpF, ER and PgR respectively) than in its absence (mean change -1.986%,-3.041 fmol mg-1 and 1.736 fmol mg-1 respectively). The progestogen main effect and the oestrogen-progestogen interaction were not significant. The rise in SpF, ER and PgR in the presence of oestrogen had a correlation coefficient with the initial ER values of -0.0565, -0.2863 and -0.1230 respectively, none being statistically significant, suggesting that the oestrogen actions were not strictly related to baseline ER concentrations. The combined median baseline ER and PgR values of the four groups were 1.48 fmol mg-1 and 0.80 fmol mg-1 respectively. Our results show that oestrogen is capable of increasing SpF in locally advanced cervical cancer in vivo and may help to revive interest in the use of oestrogen as a radiosensitizing agent in the treatment of this disease

BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei

While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis, recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle. However, these parasites lack a mitochondrial isoform of pyruvate dehydrogenase and the identity of the enzyme that catalyses the conversion of pyruvate to acetyl-CoA remains enigmatic. Here we demonstrate that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei. Deletion of the E1a subunit of T. gondii and P. berghei BCKDH significantly impacted on intracellular growth and virulence of both parasites. Interestingly, disruption of the P. berghei E1a restricted parasite development to reticulocytes only and completely prevented maturation of oocysts during mosquito transmission. Overall this study highlights the importance of the molecular adaptation of BCKDH in this important class of pathogens

Source attribution, prevalence and enumeration of Campylobacter spp. from retail liver

Funding Information: We thank Food Standards Agency, Scotland for funding this work.Peer reviewedPreprin

Long-term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial

National Institute for Health Research Efficacy and Mechanism Evaluation

Surveying Battery Cell Sections to Determine the Composition and Spatial Distribution of Discharge Products using an Automated Microprobe

Determining the spatial distribution and composition of hydrohetaerolite in polished sections of discharged Leclanché cells requires the measurement of oxygen concentrations on microcrystalline material. This can be done if the composition of the mounting medium is included in the matrix correction of raw intensities. The method of Pouchou and Pichoir (PAP) is used initially to correct raw intensities obtained from surveys of microcrystalline standard material. Mean analyses agree well with the known compositions provided a correction is made for the oxygen content of the mounting medium. The same correction is then applied to the raw data collected when surveying cell sections, yielding spatially correlated analyses of hydro-hetaerolite formed as a discharge product. The surveying technique could be applied to lead-acid, Leclanché and alkaline cells

Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum

BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. RESULTS: We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with (13)C-glucose and (13)C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. CONCLUSIONS: Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs

Regularizing Portfolio Optimization

The optimization of large portfolios displays an inherent instability to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification "pressure". This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade-off between the two, depending on the size of the available data set

Seeing two faces together: preference formation in humans and rhesus macaques

Humans, great apes and old world monkeys show selective attention to faces depending on conspecificity, familiarity, and social status supporting the view that primates share similar face processing mechanisms. Although many studies have been done on face scanning strategy in monkeys and humans, the mechanisms influencing viewing preference have received little attention. To determine how face categories influence viewing preference in humans and rhesus macaques (Macaca mulatta), we performed two eye-tracking experiments using a visual preference task whereby pairs of faces from different species were presented simultaneously. The results indicated that viewing time was significantly influenced by the pairing of the face categories. Humans showed a strong bias towards an own-race face in an Asian–Caucasian condition. Rhesus macaques directed more attention towards non-human primate faces when they were paired with human faces, regardless of the species. When rhesus faces were paired with faces from Barbary macaques (Macaca sylvanus) or chimpanzees (Pan troglodytes), the novel species’ faces attracted more attention. These results indicate that monkeys’ viewing preferences, as assessed by a visual preference task, are modulated by several factors, species and dominance being the most influential