Evidence and Spatial Planning for Sustainable Development: A Model for Spatially Allocating Material Flows

The aspiration the spatial planning should act as the main coordinating function for the transition to a sustainable society is grounded on the assumption that it is capable of incorporating both a strong evidence base of environmental accounting for policy, coupled with opportunities for open, deliberative decision-making. While there are a number of increasingly sophisticated methods (such as material flow analysis and ecological footprinting) that can be used to longitudinally determine the impact of policy, there are fewer that can provide a robust spatial assessment of sustainability policy. In this paper, we introduce the Spatial Allocation of Material Flow Analysis (SAMFA) model, which uses the concept of socio-economic metabolism to extrapolate the impact of local consumption patterns that may occur as a result of the local spatial planning process at multiple spatial levels. The initial application the SAMFA model is based on County Kildare in the Republic of Ireland, through spatial temporal simulation and visualisation of construction material flows and associated energy use in the housing sector. Thus, while we focus on an Ireland case study, the model is applicable to spatial planning and sustainability research more generally. Through the development and evaluation of alternative scenarios, the model appears to be successful in its prediction of the cumulative resource and energy impacts arising from consumption and development patterns. This leads to some important insights in relation to the differential spatial distribution of disaggregated allocation of material balance and energy use, for example that rural areas have greater resource accumulation (and are therefore in a sense “less sustainable”) than urban areas, confirming that rural housing in Ireland is both more material and energy intensive. This therefore has the potential to identify hotspots of higher material and energy use, which can be addressed through targeted planning initiatives or focussed community engagement. Furthermore, due to the ability of the model to allow manipulation of different policy criteria (increased density, urban conservation etc), it can also act as an effective basis for multi-stakeholder engagement.

Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's disease

Prefibrillar assembly of amyloid-ß (Aß) is a major event underlying the development of neuropathology and dementia in Alzheimer's disease (AD). This study determined the neuroprotective properties of an orally bioavailable Aß synaptotoxicity inhibitor, SEN1576. Binding of SEN1576 to monomeric Aß 1–42 was measured using surface plasmon resonance. Thioflavin-T and MTT assays determined the ability of SEN1576 to block Aß 1–42-induced aggregation and reduction in cell viability, respectively. In vivo long-term potentiation (LTP) determined effects on synaptic toxicity induced by intracerebroventricular (i.c.v.) injection of cell-derived Aß oligomers. An operant behavioural schedule measured effects of oral administration following i.c.v. injection of Aß oligomers in normal rats. SEN1576 bound to monomeric Aß 1–42, protected neuronal cells exposed to Aß 1–42, reduced deficits in in vivo LTP and behaviour. SEN1576 exhibits the necessary features of a drug candidate for further development as a disease modifying treatment for the early stages of AD-like dementia.

Achalasia: A review of clinical diagnosis, epidemiology, treatment and outcomes

Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function. Historically, annual achalasia incidence rates were believed to be low, approximately 0.5-1.2 per 100000. More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations. The aetiology of achalasia is still unclear but is likely to be multi-factorial. Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus, which elicits an autoimmune response. Risk of achalasia may be elevated in a sub-group of genetically susceptible people. Improvement in the diagnosis of achalasia, through the introduction of high resolution manometry with pressure topography plotting, has resulted in the development of a novel classification system for achalasia. This classification system can evaluate patient prognosis and predict responsiveness to treatment. There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller's myotomy procedure in the treatment of achalasia. A recent comparative study found equal efficacy, suggesting that patient preference and local expertise should guide the choice. Although achalasia is a relatively rare condition, it carries a risk of complications, including aspiration pneumonia and oesophageal cancer. The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia, however the absolute excess risk is small. Therefore, it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective.

Dorsal and ventral stream mediated visual processing in genetic subtypes of Prader-Willi syndrome

Previous work has suggested that there are specific deficits in dorsal stream processing in a variety of developmental disorders. Prader-Willi syndrome (PWS) is associated with two main genetic subtypes, deletion and disomy. Relative strengths in visual processing are shown in PWS, although these strengths may be specific to the deletion subtype. We investigated visual processing in PWS using an adapted Simon task which contrasted location (dorsal stream) and shape identity (ventral stream) tasks. Compared to a group of typically developing children, children with PWS deletion showed a greater degree of impairment in the dorsal stream task than in the ventral stream task, a pattern similar to that shown in a group of boys with Fragile-X syndrome. When matched on a measure of non-verbal ability, children with PWS disomy showed the opposite pattern with better performance in the location compared to the shape task, although these task performance asymmetries may have been linked to executive control processes. It is proposed that children with PWS deletion show a relative strength in visual processing in the ventral stream along with a specific deficit in dorsal stream processing. In contrast, children with PWS disomy show neither effect. (C) 2009 Published by Elsevier Ltd.

Attention-based modulation of tactile stimuli: A comparison between prefrontal lesion patients and healthy age-matched controls

Objectives: To investigate the role of the prefrontal cortex in attention-based modulation of cortical somatosensory processing.

Methods: Six prefrontal stroke patients were compared with eleven neurologically intact older adults during a vibrotactile discrimination task. All subjects attended to stimuli on one digit while ignoring distracter stimuli on a separate digit of the same hand. Subjects were required to report infrequent targets on the attended digit only. Throughout testing electroencephalography was used to measure event-related potentials for both task-relevant and irrelevant stimuli.

Results: Prefrontal patients demonstrated significant changes in cortical somatosensory processing based on attention compared to age-matched controls. This was evident both in early unimodal somatosensory processing (i.e. P100) and in later cortical processing stages (i.e. long-latency positivity). Moreover, there was a tendency towards a tonic loss of inhibition over early somatosensory cortical processing (i.e. P50).

Conclusions: The attention-based modulation noted for neurologically intact older adults was absent in prefrontal lesion patients.

Significance: The present study highlights the important role of prefrontal regions in sustaining inhibition over early sensory cortical processing stages and in modifying somatosensory transmission based on task-relevance. Notably these deficits extend beyond those previously shown to occur as a function of age.

Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642758 single nucleotide polymorphism (SNP) markers. A significant association (P=7.9×10) was found with the SNP marker rs1797052, situated in the 5′-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α=0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Augmentation mammoplasty: effect on diagnosis of breast cancer

Breast augmentation for cosmetic purposes is an increasingly common procedure in the USA and UK. In the USA in 2003, a total of 254 140 breast augmentation procedures were carried out [American Society of Plastic Surgeons, http://www.plasticsurgery.org/newsroom/ Procedural-Statistics-Press-Kit-Index.cfm9-1-2005; 2006.(1)]. It has been previously estimated that between 1 and 1.5 million women in the USA have prosthetic breast implants [Cook RR, Delongchamp RR, Woodbury M, et at. The prevalence of women with breast implants in the United States, 1989. J Clin Epidemiol 1995;48:519-25.(2)]. The UK National Breast Implant Registry has recorded a rise in the numbers of women receiving breast implants, with over 13 000 procedures registered in 2001; an estimated 77% of these were for cosmetic purposes. No association has been found between the presence of breast implants in a breast and an increased risk of breast cancer, and this subject has been comprehensively reviewed elsewhere [Hoshaw SJ, Klein PJ, Clark BD, et al. Breast implants and cancer: causation, delayed detection, and survival. Plast Reconstr Surg 2001; 107:1393-407.(3)]. However, as the population of women with breast implants ages, an increasing number of them will develop breast cancer; a reflection of the fact that the incidence of the disease increases with increasing age. Debate continues on the effect of breast implants on the efficacy of mammography in diagnosing breast cancer, and the role of other imaging techniques for this purpose, as well as the limitations that the presence of implants place on percutaneous biopsy techniques. We review the Literature on the radiological and tissue diagnosis of breast cancer in women with a history of previous augmentation mammaplasty. (c) 2007 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Freehand core biopsy in breast cancer: an accurate predictor of tumour grade following neoadjuvant chemotherapy?

Core biopsy is an increasingly used technique in the pre-operative diagnosis of breast carcinoma, as it provides useful prognostic information with respect to tumour type and grade. Neoadjuvant chemotherapy is being used in the treatment of large and locally advanced breast cancers but little is known regarding the correlation between tumour histology on pre-treatment core biopsy and that in residual tumour following primary chemotherapy and surgery. This study aimed to evaluate the accuracy of core biopsy in predicting these features in patients treated with primary chemotherapy. One hundred and thirty-three patients with carcinoma of the breast diagnosed on clinical, radiological and cytological examination underwent core biopsy, followed by primary chemotherapy (with cyclophosphamide, vincristine, doxorubicin and prednisolone) and surgery. The false-negative rate for pre-treatment core biopsy was 14%, with 91% agreement between the grade demonstrated on core biopsy and that in the residual tumour following completion of chemotherapy. Tumour type in the residual post-chemotherapy tumour was predicted by core biopsy in 84%. This study suggests that pre-treatment core biopsy histology accurately predicts residual tumour histology following primary chemotherapy and surgery in patients with breast cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

The management of radial scars of the breast - does core biopsy help?

Purpose: To compare the effectiveness of fine needle aspiration cytology (FNAC) with core biopsy (CB) in the pre-operative diagnosis of radial scar (RS) of the breast.

Patients and methods: A retrospective analysis was made of all radial scars diagnosed on surgical histology over an 8-year period. Comparison was made between the results of different preoperative needle biopsy techniques and surgical histology findings.

Results: Forty of 47 patients with a preoperative radiological diagnosis of radial scar were included in this analysis. Thirty-eight patients had impalpable lesions diagnosed on mammography and two presented with a palpable lump. FNAC (n=17) was inadequate in 47% of patients, missed two co-existing carcinomas found in this group, and gave a false positive or suspicious result for malignancy in 4 patients. CB (n=23) suggested a RS in 15 patients, but only diagnosed 4 out of 7 co-existing carcinomas found in this group.

Conclusion: CB is more accurate than FNAC in the diagnosis of RS. However, these data demonstrate that CB may offer little to assist in the management of patients with RS. In summary, this paper advocates the use of CB in any lesion with a radiological suspicion of carcinoma and diagnostic excision of all lesions thought to be typical of RS on mammography.

Challenging the SD benefits attributed to sport Mega-Events hosting

Sport Mega-event hosting faces opposition that is manifested with different intensity during the different phases of the event, from its inception as an idea to its delivery and legacy. Some Social Movements Organisations (SMOs) have acted as indefatigable monitors of the Sustainable Development (SD) dimension of sporting events in general and, in some of the most recent sport mega-events, in particular the Olympics, they have served as important advisors and facilitators. Nevertheless, in many cases we see enthusiastic supporters turning to vehemently challenging whatever positives have been associated with hosting the event. In addition, there is opposition to sport Mega-events in their entirety. That type of opposition tends to employ a holistic prism that manages to identify multiple interconnected negative aspects of hosting a sport mega-event and incorporate them into an anti-systemic discourse. It is important to bear in mind that irrespective of many proclamations to the opposite as far as megas are concerned (projects and/or events), a number of studies have demonstrated that citizen participation and democratic accountability in decision-making have been notoriously absent. After all, the idea of citizen participation in the planning of sport mega-event is essentially the public response to a plan conceived by others. There were, of course, some notable cases of democratic consultation at the early stages of bidding to host a sport mega-event but these more democratic approaches resulted in the failure of the bid (for e.g. Toronto 1996). The knowledge of this by the groups that initiated the hosting idea and the bidding process has led to discouraging in depth public consultation that may fit perfectly to the democratic process but not to the tight schedules of associated projects completion. That produces ‘autocracy against which opposition may arise’ (Hiller, 2000, p. 198). It is this democratic deficit that has led to important instances of social contestation and protest mobilizations by citizen groups as well as the more regular corps of social activists. From a perspective borrowed from the sociology of protest and social movements, sport mega-events hosting can operate as an issue that stimulates protest activities by an existing protest milieu and new actors as well as an important mobilizing resource. In fact, some scholars have also argued that the Olympic Games were an important frame for the transnational activism that was marked by anti-globalization protest in Seattle in 1999 (Cottrell & Nelson, 201; Lenskyj, 2008). In addition, it’s important not to lose sight of other acts dissent that take place in relatively close proximity, about a year before the event when most infrastructural and societal changes brought by hosting the event and impact start to become apparent by the host communities, like the rioting of August 2011 in the London Olympic Boroughs and the 2012 riots of June 2013 in Sao Paulo and other Brazilian cities. This paper starts by outlining the SD claims made in the bidding to host the summer Olympic Games by five prospective hosts (Sydney; Athens; Beijing; London and Rio) proceeds towards examining the opposition and challenges that was manifested in relation to these claims. In Particular it provides an assessment of protest-events over the aforementioned different phases of sport mega-events hosting. A different picture emerges for each of the host nation that is partly explained by local, national and global configuration of protest politics. Whereas the post-event legacy of the first two hosts of the Games can be assessed and that way see the validity of claims made by challengers in the other phases, in the other three cases, the implementation of Olympic Games Impact (OGI) studies offers the tool for discussing the post-event phase for Beijing and London and engage in a speculative exercise for the case of Rio. Judging by available findings, the paper concludes that the SD aspiration made in the bid documents are unlikely to be met and social contestation based on the same issues is likely to increase due to the current global economic crisis and BRICS, like China and Brazil, having entered the process of becoming global economic hegemons.

Impact of abuse and neglect on the health and wellbeing of children:Child sexual abuse

During the past 30 years, the focus on the extent and nature of child abuse and neglect has been coupled with an increasing interest in the impact on children’s development, health and mental wellbeing. Child maltreatment is both a human rights violation and a complex public health issue, likely caused by a myriad of factors that involve the individual, the family, and the community. Child abuse includes any type of maltreatment or harm inflicted upon children and young people in interactions between adults (or older adolescents). Such maltreatment is likely to cause enduring harm to the child.
The different forms of abuse and neglect often occur together in one family and can affect one or more children. These include, in deceasing level of frequency: neglect; physical abuse and non-accidental injury; emotional abuse; and sexual abuse (Cawson et al, 2000; 2002). Recently, bullying and domestic violence have been included as forms of abuse of children.
There is a sizeable body of literature on the relationship between types of child maltreatment and a variety of negative health and mental health consequences. These include biological, psychological, and social deficits (for reviews, see Crittenden, 1998; Kendall-Tackett, 2001; 2003). Aside from the serious physical and health consequences of child maltreatment, several emotional and behavioural consequences for children have been noted in the literature.

Ageing through Austerity: critical perspectives from Ireland

The book’s main contribution is the bringing together of varied discourses concerning the social policy impact of ageing within the context of fiscal austerity. As the editors rightly state, the economic recession has sharpened the focus of governments on the implication of demographic ageing. It is vital therefore, that the social policy implications of societal ageing are studied and understood within a wider political economy of austerity. Of course the fiscal crisis of the 1970s and the ensuing first wave of neo-liberalism in the Anglo-Saxon countries [in the 1980s] gave us a foretaste of the various ways in which the public burden thesis has been applied with great force to the older population. This recession is different, certainly in Ireland, but a combination of neo-liberal ideology and neo-classical economics is enforcing severe budgetary constraint on a range of countries (within and outside of the Eurozone) in the name of funding deficits. Policy makers appear to be disinterested in both the origins of the 2008 financial crisis and the distributional consequences of their austerity policies. In the absence of official concern social science research has a key role to play.

Effects of thyroxine treatment on histology and behavior using the methimazole model of congenital hypothyroidism in the rat

The timing of thyroxine (T4) replacement treatment in congenital hypothyroidism (CH) has been suggested to be important for optimizing cognitive recovery in humans; however this has not been fully established using modern animal models of CH. Consequently, the current studies investigated the ameliorating effects of postnatal T4 treatment on neuropathology and behavior in CH rats. Rat dams were administered methimazole to produce CH offspring, then brain tissue from male CH pups was analyzed to determine the effects of postnatal (P3, P7, P14 and P21) T4 treatment on hippocampal dendritic branching and the expression of nerve growth factor (NGF). Two operant behavioral procedures were employed to confirm and extend previous findings obtained using this model, and to investigate timelines for instigating T4 treatment on improved behavioral outcomes. T4 treatment initiated at P14 was protective of a reduction in dendritic branching in the hippocampus, and initiated at P7 was protective of a reduction of NGF expression in the fimbria of the hippocampus. Induction of CH did not affect the acquisition of simple operant response rules but had a significant effect on the acquisition of complex operant rules subsequently imposed. Furthermore, T4 treatment initiated at P3 protected learning deficits seen following the imposition of complex operant response rules. These findings indicate T4 treatment initiated at P7 is sufficient for the protection of hippocampal NGF expression and dendritic branching but for the protection of complex behavioral abilities T4 treatment is necessary prior to or approximating P3.

Exercise rehabilitation following intensive care unit discharge for recovery from critical illness

Background: Skeletal muscle wasting and weakness are significant complications of critical illness, associated with the degree of illness severity and periods of reduced mobility during mechanical ventilation. They contribute to the profound physical and functional deficits observed in survivors. These impairments may persist for many years following discharge from the intensive care unit (ICU) and may markedly influence health-related quality of life. Rehabilitation is a key strategy in the recovery of patients following critical illness. Exercise based interventions are aimed at targeting this muscle wasting and weakness. Physical rehabilitation delivered during ICU admission has been systematically evaluated and shown to be beneficial. However its effectiveness when initiated after ICU discharge has yet to be established. Objectives: To assess the effectiveness of exercise rehabilitation programmes, initiated after ICU discharge, on functional exercise capacity and health-related quality of life in adult ICU survivors who have been mechanically ventilated for more than 24 hours. Search methods:We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), OvidSP MEDLINE, Ovid SP EMBASE, and CINAHL via EBSCO host to 15th May 2014. We used a specific search strategy for each database. This included synonyms for ICU and critical illness, exercise training and rehabilitation. We searched the reference lists of included studies and contacted primary authors to obtain further information regarding potentially eligible studies. We also searched major clinical trials registries (Clinical Trials and Current Controlled Trials) and the personal libraries of the review authors. We applied no language or publication restriction. We reran the search in February 2015. We will deal with any studies of interest when we update the review.  Selection criteria:We included randomized controlled trials (RCTs), quasi-RCTs, and controlled clinical trials (CCTs) that compared an exercise interventioninitiated after ICU discharge to any other intervention or a control or ‘usual care’ programme in adult (≥18years) survivors ofcritical illness. Data collection and analysis:We used standard methodological procedures expected by The Cochrane Collaboration. Main results:We included six trials (483 adult ICU participants). Exercise-based interventions were delivered on the ward in two studies; both onthe ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to the length of stay in hospital following ICU discharge (up to a fixed duration of 12 weeks).Risk of bias was variable for all domains across all trials. High risk of bias was evident in all studies for performance bias, although blinding of participants and personnel in therapeutic rehabilitation trials can be pragmatically challenging. Low risk of bias was at least 50% for all other domains across all trials, although high risk of bias was present in one study for random sequence generation (selection bias), incomplete outcome data (attrition bias) and other sources. Risk of bias was unclear for remaining studies across the domains.All six studies measured effect on the primary outcome of functional exercise capacity, although there was wide variability in natureof intervention, outcome measures and associated metrics, and data reporting. Overall quality of the evidence was very low. Only two studies using the same outcome measure for functional exercise capacity, had the potential for pooling of data and assessment of heterogeneity. On statistical advice, this was considered inappropriate to perform this analysis and study findings were therefore qualitatively described. Individually, three studies reported positive results in favour of the intervention. A small benefit (versus. control)was evident in anaerobic threshold in one study (mean difference, MD (95% confidence interval, CI), 1.8 mlO2/kg/min (0.4 to 3.2),P value = 0.02), although this effect was short-term, and in a second study, both incremental (MD 4.7 (95% CI 1.69 to 7.75) Watts, P value = 0.003) and endurance (MD 4.12 (95% CI 0.68 to 7.56) minutes, P value = 0.021) exercise testing demonstrated improvement.Finally self-reported physical function increased significantly following a rehabilitation manual (P value = 0.006). Remaining studies found no effect of the intervention.Similar variability in with regard findings for the primary outcome of health-related quality of life were also evident. Only two studies evaluated this outcome. Following statistical advice, these data again were considered inappropriate for pooling to determine overall effect and assessment of heterogeneity. Qualitative description of findings was therefore undertaken. Individually, neither study reported differences between intervention and control groups for health-related quality of life as a result of the intervention. Overall quality of the evidence was very low.Mortality was reported by all studies, ranging from 0% to 18.8%. Only one non-mortality adverse event was reported across all patients in all studies (a minor musculoskeletal injury). Withdrawals, reported in four studies, ranged from 0% to 26.5% in control groups,and 8.2% to 27.6% in intervention groups. Loss to follow-up, reported in all studies, ranged from 0% to 14% in control groups, and 0% to 12.5% in intervention groups. Authors’ conclusions:We are unable, at this time, to determine an overall effect on functional exercise capacity, or health-related quality of life, of an exercise based intervention initiated after ICU discharge in survivors of critical illness. Meta-analysis of findings was not appropriate. This was due to insufficient study number and data. Individual study findings were inconsistent. Some studies reported a beneficial effect of the intervention on functional exercise capacity, and others not. No effect was reported on health-related quality of life. Methodological rigour was lacking across a number of domains influencing quality of the evidence. There was also wide variability in the characteristics of interventions, outcome measures and associated metrics, and data reporting.If further trials are identified, we may be able to determine the effect of exercise-based interventions following ICU discharge, on functional exercise capacity and health-related quality of life in survivors of critical illness.

Common causes and current guidelines

Chronic cough is a common and disabling symptom. Recent guidelines have attempted to provide direction in the clinical management of cough in both primary and secondary care. They have also provided a critical review of the available literature and identified gaps in current knowledge. Despite this they have been criticized for a reliance on a low quality evidence base. In this review, we summarize the current consensus on the clinical management of chronic cough and attempt to rationalize this based on recent evidence. We have also provided an overview of the likely pathophysiological mechanisms responsible for cough and highlighted areas, where knowledge deficits exist and suggest directions for future research. Such progress will be critical in the search for new and effective treatments for cough.