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The article compares the guide dog movements in the United States and England, noting that in England there is one school with 7 centers while in the U.S. there are 10 competing schools. In England, twice as high a proportion of blind people use guide dogs. (Author/DB)

Background The role of α-adrenoceptors in promoting continence through modulation of sphincter tone has focused primarily on the effects of α1-adrenoceptors. We have used three clinically available agents, which are selective for α2-adrenoceptors, to investigate their role in contractile and neurogenic responses on the internal anal sphincter ( IAS). Methods IAS strips, which had spontaneously generated tone, were used to investigate the contractile effect of lofexidine, brimonidine, and dexmedetomidine on muscle tone in the presence or absence of subtype selective antagonists. The effect of brimonidine on the magnitude and time course of neurogenic responses generated by electrical field stimulation ( EFS) was also examined. The affinity of test compounds at α1- and α2-adrenoceptors was established by competition binding with [3H]-prazosin and [3H]- RX821002. Key Results All agonists caused concentration-dependent contraction of the IAS and lofexidine demonstrated an enantiomeric difference in potency with a 10-fold difference between the (−) and (+) isomers. Responses to lofexidine and dexmedetomidine were inhibited in the presence of the α1-adrenoceptor selective antagonist prazosin, but not in the presence of RX811059 ( α2-adrenoceptor selective antagonist); brimonidine responses were inhibited by RX811059 and, to a lesser extent, by prazosin. Brimonidine affected both magnitude and duration of neurogenic responses, which was reversed in the presence of RX811059. Conclusions & Inferences We conclude that α2-adrenoceptors can mediate contraction of IAS, although this effect is most evident with efficacious imidazoline agonists rather than the most selective ligand. In addition, this receptor subtype can directly inhibit noradrenergic contractile responses to EFS and, indirectly, enhance nitrergic relaxatory responses. [ABSTRACT FROM AUTHOR]

Background and Purpose: We have investigated the distribution of alpha-adrenoceptors in sheep internal anal sphincter (IAS), as a model for the human tissue, and evaluated various imidazoline derivatives for potential treatment of faecal incontinence.Experimental Approach: Saturation and competition binding with (3)H-prazosin and (3)H-RX821002 were used to confirm the presence and density of alpha-adrenoceptors in sheep IAS, and the affinity of imidazoline compounds at these receptors. A combination of in vitro receptor autoradiography and immunohistochemistry was used to investigate the regional distribution of binding sites. Contractile activity of imidazoline-based compounds on sheep IAS was assessed by isometric tension recording.Key Results: Saturation binding confirmed the presence of both alpha(1)- and alpha(2)-adrenoceptors, and subsequent characterization with sub-type-selective agents, identified them as alpha(1A)- and alpha(2D)-adrenoceptor sub-types. Autoradiographic studies with (3)H-prazosin showed a positive association of alpha(1)-adrenoceptors with immunohistochemically identified smooth muscle fibres. Anti-alpha(1)-adrenoceptor immunohistochemistry revealed similar distributions of the receptor in sheep and human IAS. The imidazoline compounds caused concentration-dependent contractions of the anal sphincter, but the maximum responses were less than those elicited by l-erythro-methoxamine, a standard non-imidazoline alpha(1)-adrenoceptor agonist. Prazosin (selective alpha(1)-adrenoceptor antagonist) significantly reduced the magnitude of contraction to l-erythro-methoxamine at the highest concentration used. Both prazosin and RX811059 (a selective alpha(2)-adrenoceptor antagonist) reduced the potency (pEC(50)) of clonidine.Conclusions and Implications: This study shows that both alpha(1)- and alpha(2)-adrenoceptors are expressed in the sheep IAS, and contribute (perhaps synergistically) to contractions elicited by various imidazoline derivatives. These agents may prove useful in the treatment of faecal incontinence. [ABSTRACT FROM AUTHOR]

Fire management across Australia's fire-prone 1.2 M km 2 northern savannas region has been transformed over the past decade supported by the inception of Australia's national regulated emissions reduction market in 2012. Today, incentivised fire management is undertaken over a quarter of that entire region, providing a range of socio-cultural, environmental, and economic benefits, including for remote Indigenous (Aboriginal and Torres Strait Islander) communities and enterprises. Building on those advances, here we explore the emissions abatement potential for expanding incentivised fire management opportunities to include a contiguous fire-prone region, extending to monsoonal but annually lower (<600 mm) and more variable rainfall conditions, supporting predominantly shrubby spinifex (Triodia) hummock grasslands characteristic of much of Australia's deserts and semi-arid rangelands. Adapting a standard methodological approach applied previously for assessing savanna emissions parameters, we first describe fire regime and associated climatic attributes for a proposed ∼850,000 km 2 lower rainfall (600-350 mm MAR) focal region. Second, based on regional field assessments of seasonal fuel accumulation, combustion, burnt area patchiness, and accountable methane and nitrous oxide Emission Factor parameters, we find that significant emissions abatement is feasible for regional hummock grasslands. This applies specifically for more frequently burnt sites under higher rainfall conditions if substantial early dry season prescribed fire management is undertaken resulting in marked reduction in late dry season wildfires. The proposed Northern Arid Zone (NAZ) focal envelope is substantially under Indigenous land ownership and management, and in addition to reducing emissions impacts associated with recurrent extensive wildfires, development of commercial landscape-scale fire management opportunities would significantly support social, cultural and biodiversity management aspirations as promoted by Indigenous landowners. Combined with existing regulated savanna fire management regions, inclusion of the NAZ under existing legislated abatement methodologies would effectively provide incentivised fire management covering a quarter of Australia's landmass. This could complement an allied (non-carbon) accredited method valuing combined social, cultural and biodiversity outcomes from enhanced fire management of hummock grasslands. Although the management approach has potential application to other international fire-prone savanna grasslands, caution is required to ensure that such practice does not result in irreversible woody encroachment and undesirable habitat change., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by Indigenous Land And Sea Corporation. All authors reports financial support was provided by The Nature Conservancy. All authors reports financial support was provided by Northern Territory Government Department of Environment, Parks and Water Security. All authors reports financial support was provided by Central Land Council. All authors reports financial support was provided by Kimberley Land Council. All authors reports financial support was provided by 10 Deserts Project., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Savanna fires occurring in sub-Saharan Africa account for over 60% of global fire extent, of which more than half occurs in the Southern Hemisphere contributing ~29% of global fire emissions. Building on experience in reducing savanna fire emissions in fire-prone north Australian savannas through implementation of an internationally accredited 'savanna burning' emissions abatement methodology, we explore opportunities and challenges associated with the application of a similar approach to incentivise emissions reduction in fire-prone southern African savannas. We first show that for a focal region covering seven contiguous countries, at least 80% of annual savanna large fire (>250 ha) extent and emissions occur under relatively severe late dry season (LDS) fire-weather conditions, predominantly in sparsely inhabited areas. We then assess the feasibility of adapting the Australian emissions abatement methodology through exploratory field studies at the Tsodilo Hills World Heritage site in north-west Botswana, and the Niassa Special Reserve in northern Mozambique. Our assessment demonstrates that application of a savanna burning emissions abatement method focused on the undertaking of strategically located early dry season (EDS) burning to reduce LDS wildfire extent and resultant emissions meets key technical criteria, including: LDS fine fuels tend to be markedly greater than EDS fuels given seasonal leaf litter inputs; LDS fires tend to be significantly more severe and combust more fuels; methane and nitrous oxide emission factors are essentially equivalent in EDS and LDS periods under cured fuel conditions. In discussion we consider associated key implementation challenges and caveats that need to be addressed for progressing development of savanna burning methods that incentivise sustainable fire management, reduce emissions, and support community livelihoods in wildfire-dominated southern African savannas., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The study, a two-arm, randomized controlled, parallel group, superiority trial, aimed to evaluate the implementation and effectiveness of a 12-month one-to-one volunteer mentoring program designed to improve behavioral and emotional outcomes in children aged 5 to 11 years who have teacher- and parent/carer-reported behavioral difficulties. Participants were 246 children (123 intervention, 123 control; mean age 8.4 years; 87% boys) in five sites in London, UK, scoring in the "abnormal" range on the teacher-rated Strengths and Difficulties Questionnaire (SDQ) Total Difficulties measure and in the "borderline" or abnormal range on the parent-rated SDQ Total Difficulties measure. Randomization on a 1:1 ratio took place using a computer-generated sequence and stratifying by site. Data collectors and statisticians were blind to participant allocation status. Outcome measures focused on parent- and teacher-rated child behavior and emotions, and child-rated self-perception and hope. Intention-to-treat analysis on all 246 randomized participants (using imputed data where necessary) showed that at post-intervention (16 months after randomization), there were no statistically significant effects on the primary outcome-parent-rated SDQ Total Difficulties (adjusted standardized mean difference = - 0.12; 95% CI: -0.38 to 0.13; p = 0.33)-or any secondary outcomes. Results from complier average causal effect (CACE) analysis using the primary outcome indicated the intervention was not effective for children who received the recommended duration of mentoring. Exploratory analyses found no sub-group effects on the primary outcome. The article concludes that the mentoring program had no effect on children's behavior or emotional well-being, and that program content needs revising to satisfactorily address key risk and protective factors.

Loop-mediated isothermal amplification (LAMP) has gained wide popularity in the detection of Salmonella in foods owing to its simplicity, rapidity, and robustness. This multi-laboratory validation (MLV) study aimed to validate a Salmonella LAMP-based method against the United States Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) Chapter 5 Salmonella reference method in a representative animal food matrix (dry dog food). Fourteen independent collaborators from seven laboratories in the United States and Canada participated in the study. Each collaborator received two sets of 24 blind-coded dry dog food samples (eight uninoculated; eight inoculated at a low level, 0.65 MPN/25 g; and eight inoculated at a high level, 3.01 MPN/25 g) and initiated the testing on the same day. The MLV study used an unpaired design where different test portions were analyzed by the LAMP and BAM methods using different preenrichment protocols (buffered peptone water for LAMP and lactose broth for BAM). All LAMP samples were confirmed by culture using the BAM method. BAM samples were also tested by LAMP following lactose broth preenrichment (paired samples). Statistical analysis was carried out by the probability of detection (POD) per AOAC guidelines and by a random intercept logistic regression model. Overall, no significant differences in POD between the Salmonella LAMP and BAM methods were observed with either unpaired or paired samples, indicating the methods were comparable. LAMP testing following preenrichment in buffered peptone water or lactose broth also resulted in insignificant POD differences ( P > 0.05). The MLV study strongly supports the utility and applicability of this rapid and reliable LAMP method in routine regulatory screening of Salmonella in animal food.

Background: There is a need to build the evidence base of early interventions to promote children's health and development in the UK. Chance UK is a voluntary sector organisation based in London that delivers a 12-month mentoring programme for primary school children identified by teachers and parents as having behavioural and emotional difficulties. The aim of the study is to determine the effectiveness of the programme in terms of children's behaviour and emotional well-being; this is the primary outcome of the trial., Methods/design: A randomised controlled trial will be conducted in which participants are randomly allocated on a dynamic basis to one of two possible arms: the intervention arm (n = 123) will be offered the mentoring programme, and the control arm (n = 123) will be offered services as usual. Outcome data will be collected at three points: pre-intervention (baseline), mid-way through the mentoring year (c.9 months after randomisation) and post- mentoring programme (c.16 months after randomisation)., Discussion: This study will further enhance the evidence for early intervention mentoring programmes for child behaviour and emotional well-being in the UK., Trial Registration: Current Controlled Trials ISRCTN47154925 . Retrospectively registered 9 September 2014.

Background: There is a need to build the evidence base of early interventions promoting children's health and development in the UK. Malachi Specialist Family Support Services ('Malachi') is a voluntary sector organisation based in the UK that delivers a therapeutic parenting group programme called Inspiring Futures to parents of children identified as having behavioural and emotional difficulties. The programme comprises two parts, delivered sequentially: (1) a group-based programme for all parents for 10-12 weeks, and (2) one-to-one sessions with selected parents from the group-based element for up to 12 weeks., Methods/design: A randomised controlled trial will be conducted to evaluate Malachi's Inspiring Futures parenting programme. Participants will be allocated to one of two possible arms, with follow-up measures at 16 weeks (post-parent group programme) and at 32 weeks (post-one-to-one sessions with selected parents). The sample size is 248 participants with a randomisation allocation ratio of 1:1. The intervention arm will be offered the Inspiring Futures programme. The control group will receive services as usual. The aim is to determine the effectiveness of the Inspiring Futures programme on the primary outcome of behavioural and emotional difficulties of primary school children identified as having behavioural or emotional difficulties., Discussion: This study will further enhance the evidence for early intervention parenting programmes for child behavioural and emotional problems in the UK., Trial Registration: Current Controlled Trials ISRCTN32083735 . Retrospectively registered 28 October 2014.

Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Background: In recent years inhibitors directed against the epidermal growth factor receptor (EGFR) have evolved as effective targeting cancer drugs. Characteristic papulopustular exanthemas, often described as acneiform rashes, are the most frequent adverse effect associated with this class of novel cancer drugs and develop in > 90% of patients. Notably, the rash may significantly compromise the patients' quality of life, thereby potentially leading to incompliance as well as dose reduction or even termination of the anti-EGFR therapy. Yet, an effective dermatologic management of cutaneous adverse effects can be achieved. Whereas various case reports, case series or expert opinions on the management of EGFR-inhibitor (EGFRI) induced rashes have been published, data on systematic management studies are sparse., Methods: Here, we present a retrospective, uncontrolled, comparative study in 49 patients on three established regimens for the management of EGFRI-associated rashes., Results: Strikingly, patients' rash severity improved significantly over three weeks of treatment with topical mometason furoate cream, topical prednicarbate cream plus nadifloxacin cream, as well as topical prednicarbate cream plus nadifloxacin cream plus systemic isotretinoin., Conclusions: In summary our results demonstrate that EGFRI-associated rashes can be effectively managed by specific dermatologic interventions. Whereas mild to moderate rashes should be treated with basic measures in combination with topical glucocorticosteroids or combined regiments using glucocorticosteroids and antiseptics/antibiotics, more severe or therapy-resistant rashes are likely to respond with the addition of systemic retinoids.

In the literature, non-ablative fractionated photothermolysis (nFP) is accredited with improvement of wrinkles and scars combined with a reduced downtime. The purpose of this work was to evaluate the impact of a combination laser (1,320/1,440 nm) for nFP on hypertrophic scars, acne scars, and facial wrinkles. Thirty-six patients suffering from hypertrophic scars (n = 7), acne scars (n = 9), and wrinkles (n = 20) were treated using a combination Nd:YAG laser [λ(em) = 1,320 and 1,440 nm, pulse duration: 3-ms single pulse, fluence: 8.0-9.0 J/cm(2) (1,320 nm); 2.0-2.5 J/cm(2) (1,440 nm)]. The appearance of the treated condition was evaluated in a retrospective study by two blinded investigators based on follow-up photographs and by patient self-assessment. The frequency of side-effects was also assessed. Both patients and blinded observers rated the treatment results for hypertrophic scars and acne scars as slight improvement, and for wrinkles as equal as compared to baseline. No serious side-effects were reported. The light device used did not lead to a considerable clinical improvement of hypertrophic scars, acne scars, or wrinkles in this study.

Pattern analysis of skin lesions is an art and a key competence of every dermatologist. Three major line patterns cover the human body-the dermatomes or Head zones, the nevoid lines of Blaschko, and the relaxed skin tension lines, or Langer lines. Head zones represent skin areas innervated from the same sensory neuronal segment or spinal nerve zone. Blaschko lines are borderlines of epidermal aberration caused by genetic mosaicism occurring in the early stages of embryogenesis. Langer lines show the direction of the lowest naturally occurring skin tension, and its thoracodorsal manifestation is the Christmas tree pattern. Here we review clinical aspects of pityriasis rosea, mycosis fungoides, stage 2 syphilis, exanthematic Kaposi sarcoma, exanthematic psoriasis, Leser-Trelat syndrome, and other primary skin diseases with a Christmas tree pattern. Secondary skin diseases, such as herpes zoster or indeterminate cell histiocytosis, may follow this pattern if they are linked to a primary skin disease by the Wolf isotopic response., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: So far, pulsed dye lasers have been regarded as the gold standard in the treatment of port-wine stains (PWS). Recently, intense pulsed light (IPL) has been reported to achieve more pronounced fading in some patients., Objectives: To evaluate the efficacy and the side effects of IPL treatment of PWS in a direct comparison to the short-pulsed dye laser (SPDL) and the long-pulsed dye laser (LPDL)., Methods: Test spots (n = 158) were applied with IPL (λ(em) = 555-950 nm, pulse duration: 8-14 milliseconds (single pulse), fluence: 11-17.3 J/cm(2)), the SPDL (λ(em) = 585 nm, pulse duration: 0.45 milliseconds, fluence: 6 J/cm(2)), and the LPDL (λ(em) = 585/590/595/600 nm, pulse duration: 1.5 milliseconds, fluence: 12/14/16/18 J/cm(2)) in a side-by-side modus in untreated (n = 11) and previously treated (n = 14) patients with PWS. Lesion clearance was evaluated by three blinded investigators based on follow-up photographs 6 weeks after treatment. Incidence of side effects was assessed., Results: In previously untreated PWS as well as in pretreated PWS, IPL treatments were rated significantly (P<0.05) better than treatments with the SPDL. In both groups, IPL and LPDL treatments did not differ significantly. Side effects were few in all settings., Conclusions: In PWS resistant to dye laser therapy, IPL showed additional lesion clearance. The use of IPL increases the therapeutic possibilities in PWS., (© 2010 Wiley-Liss, Inc.)