Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators

This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal)

Theory of Multidimensional Solitons

We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Evaluation of Lay Support in Pregnant women with Social risk (ELSIPS): a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Maternal, neonatal and child health outcomes are worse in families from black and ethnic minority groups and disadvantaged backgrounds. There is little evidence on whether lay support improves maternal and infant outcomes among women with complex social needs within a disadvantaged multi-ethnic population in the United Kingdom (UK).</p> <p>Method/Design</p> <p>The aim of this study is to evaluate a lay Pregnancy Outreach Worker (POW) service for nulliparous women identified as having social risk within a maternity service that is systematically assessing social risks alongside the usual obstetric and medical risks. The study design is a randomised controlled trial (RCT) in nulliparous women assessed as having social risk comparing standard maternity care with the addition of referral to the POW support service.</p> <p>The POWs work alongside community midwifery teams and offer individualised support to women to encourage engagement with services (health and social care) from randomisation (before 28 weeks gestation) until 6 weeks after birth.</p> <p>The primary outcomes have been chosen on the basis that they are linked to maternal and infant health. The two primary outcomes are engagement with antenatal care, assessed by the number of antenatal visits; and maternal depression, assessed using the Edinburgh Postnatal Depression Scale at 8-12 weeks after birth. Secondary outcomes include maternal and neonatal morbidity and mortality, routine child health assessments, including immunisation uptake and breastfeeding at 6 weeks. Other psychological outcomes (self efficacy) and mother-to-infant bonding will also be collected using validated tools.</p> <p>A sample size of 1316 will provide 90% power (at the 5% significance level) to detect increased engagement with antenatal services of 1.5 visits and a reduction of 1.5 in the average EPDS score for women with two or more social risk factors, with power in excess of this for women with any social risk factor. Analysis will be by intention to treat.</p> <p>Qualitative research will explore the POWs' daily work in context. This will complement the findings of the RCT through a triangulation of quantitative and qualitative data on the process of the intervention, and identify other contextual factors that affect the implementation of the intervention.</p> <p>Discussion</p> <p>The trial will provide high quality evidence as to whether or not lay support (POW) offered to women identified with social risk factors improves engagement with maternity services and reduces numbers of women with depression.</p> <p>MREC number</p> <p>10/H1207/23</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN35027323">ISRCTN35027323</a></p

Dopamine Signaling Is Essential for Precise Rates of Locomotion by C. elegans

Dopamine is an important neuromodulator in both vertebrates and invertebrates. We have found that reduced dopamine signaling can cause a distinct abnormality in the behavior of the nematode C. elegans, which has only eight dopaminergic neurons. Using an automated particle-tracking system for the analysis of C. elegans locomotion, we observed that individual wild-type animals made small adjustments to their speed to maintain constant rates of locomotion. By contrast, individual mutant animals defective in the synthesis of dopamine made larger adjustments to their speeds, resulting in large fluctuations in their rates of locomotion. Mutants defective in dopamine signaling also frequently exhibited both abnormally high and abnormally low average speeds. The ability to make small adjustments to speed was restored to these mutants by treatment with dopamine. These behaviors depended on the D2-like dopamine receptor DOP-3 and the G-protein subunit GOA-1. We suggest that C. elegans and other animals, including humans, might share mechanisms by which dopamine restricts motor activity levels and coordinates movement

Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial

Background: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. Methods: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L-leucine), or nothing (Control). In EXP1, participants (n=10, 68±5 years, mean±SD) consumed Bar, Gel or Control with appetite sensations and appetite-related hormonal responses monitored for one hour, followed by consumption of an ad libitum breakfast (ALB). In EXP2, participants (n=11, 69±5 years) ingested Bar, Gel or Control alongside an ALB. Results: In EXP1, EI at ALB was not different (P=0.674) between conditions (1179±566, 1254±511, 1206±550 kJ for the Control, Bar, and Gel respectively). However, total EI was significantly higher in the Bar and Gel compared to the Control after accounting for the energy content of the supplements (P<0.0005). Analysis revealed significantly higher appetite Area under the Curve (AUC) (P<0.007), a tendency for higher acylated ghrelin AUC (P=0.087), and significantly lower pancreatic polypeptide AUC (P=0.02) in the Control compared with the Bar and Gel. In EXP2, EI at ALB was significantly higher (P=0.028) in the Control (1282±513 kJ) compared to the Bar (1026±565 kJ) and Gel (1064±495 kJ). However, total EI was significantly higher in the Bar and Gel after accounting for the energy content of the supplements (P<0.007). Conclusions: Supplementation with either the Bar or Gel increased total energy intake whether consumed one hour before or during breakfast. This may represent an effective nutritional means for addressing protein and total energy deficiencies in older women

Alexithymia, but not Autism Spectrum Disorder, may be Related to the Production of Emotional Facial Expressions

Background A prominent diagnostic criterion of autism spectrum disorder (ASD) relates to the abnormal or diminished use of facial expressions. Yet little is known about the mechanisms that contribute to this feature of ASD. Methods We showed children with and without ASD emotionally charged video clips in order to parse out individual differences in spontaneous production of facial expressions using automated facial expression analysis software. Results Using hierarchical multiple regression, we sought to determine whether alexithymia (characterized by difficulties interpreting one’s own feeling states) contributes to diminished facial expression production. Across groups, alexithymic traits—but not ASD traits, IQ, or sex—were associated with quantity of facial expression production. Conclusions These results accord with a growing body of research suggesting that many emotion processing abnormalities observed in ASD may be explained by co-occurring alexithymia. Developmental and clinical considerations are discussed, and it is argued that alexithymia is an important but too often ignored trait associated with ASD that may have implications for subtyping individuals on the autism spectrum

Rodent Models of TDP-43 Proteinopathy: Investigating the Mechanisms of TDP-43-Mediated Neurodegeneration

Since the identification of phosphorylated and truncated transactive response DNA-binding protein 43 (TDP-43) as a primary component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions, much effort has been directed towards ascertaining how TDP-43 contributes to the pathogenesis of disease. As with other protein misfolding disorders, TDP-43-mediated neuronal death is likely caused by both a toxic gain and loss of TDP-43 function. Indeed, the presence of cytoplasmic TDP-43 inclusions is associated with loss of nuclear TDP-43. Moreover, post-translational modifications of TDP-43, including phosphorylation, ubiquitination, and cleavage into C-terminal fragments, may bestow toxic properties upon TDP-43 and cause TDP-43 dysfunction. However, the exact neurotoxic TDP-43 species remain unclear, as do the mechanism(s) by which they cause neurotoxicity. Additionally, given our incomplete understanding of the roles of TDP-43, both in the nucleus and the cytoplasm, it is difficult to truly appreciate the detrimental consequences of aberrant TDP-43 function. The development of TDP-43 transgenic animal models is expected to narrow these gaps in our knowledge. The aim of this review is to highlight the key findings emerging from TDP-43 transgenic animal models and the insight they provide into the mechanisms driving TDP-43-mediated neurodegeneration

Promoting fit bodies, healthy eating and physical activity among Indigenous Australian men: a study protocol

Background: Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia&rsquo;s Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a communitybased investigation into the factors surrounding the health and body image of Indigenous Australian men.Methods and design: The study will be conducted in a collaborative manner with Indigenous Australian men using a participatory action research framework. Men will be recruited from three locations around Australia (metropolitan, regional, and rural) and interviewed to understand their experiences and perspectives on a number of issues related to health and health behaviour. The information that is collected will be analysed using modified grounded theory and thematic analysis. The results will then be used to develop and implement community events in each location to provide feedback on the findings to the community, promote health enhancing strategies, and determine future action and collaboration.Discussion: This study will explore both risk and protective factors that affect the health of Indigenous Australian men. This knowledge will be disseminated to the wider Indigenous community and can be used to inform future health promotion strategies. The expected outcome of this study is therefore an increased understanding of health and health change in Indigenous Australian men, the development of strategies that promote healthy eating and positive patterns of physical activity and, in the longer term, more effective and culturally-appropriate interventions to improve health.<br /

Coaggregation of RNA-Binding Proteins in a Model of TDP-43 Proteinopathy with Selective RGG Motif Methylation and a Role for RRM1 Ubiquitination

TAR DNA-binding protein 43 (TDP-43) is a major component within ubiquitin-positive inclusions of a number of neurodegenerative diseases that increasingly are considered as TDP-43 proteinopathies. Identities of other inclusion proteins associated with TDP-43 aggregation remain poorly defined. In this study, we identify and quantitate 35 co-aggregating proteins in the detergent-resistant fraction of HEK-293 cells in which TDP-43 or a particularly aggregate prone variant, TDP-S6, were enriched following overexpression, using stable isotope-labeled (SILAC) internal standards and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). We also searched for differential post-translational modification (PTM) sites of ubiquitination. Four sites of ubiquitin conjugation to TDP-43 or TDP-S6 were confirmed by dialkylated GST-TDP-43 external reference peptides, occurring on or near RNA binding motif (RRM) 1. RRM-containing proteins co-enriched in cytoplasmic granular structures in HEK-293 cells and primary motor neurons with insoluble TDP-S6, including cytoplasmic stress granule associated proteins G3BP, PABPC1, and eIF4A1. Proteomic evidence for TDP-43 co-aggregation with paraspeckle markers RBM14, PSF and NonO was also validated by western blot and by immunocytochemistry in HEK-293 cells. An increase in peptides from methylated arginine-glycine-glycine (RGG) RNA-binding motifs of FUS/TLS and hnRNPs was found in the detergent-insoluble fraction of TDP-overexpressing cells. Finally, TDP-43 and TDP-S6 detergent-insoluble species were reduced by mutagenesis of the identified ubiquitination sites, even following oxidative or proteolytic stress. Together, these findings define some of the aggregation partners of TDP-43, and suggest that TDP-43 ubiquitination influences TDP-43 oligomerization