Rethinking zoning for people: Utilizing the concept of the village

In this chapter, we propose it is time to re-think and re-imagine how we approach zoning. This is especially true for suburban developments. Today, especially in the United States, zoning in suburban areas is being used to segregate and separate the component parts of our communities into distinct zones which are spread out geographically and in most cases require the daily use of an automobile. The negative consequences of this form of development for health, community and the environment are discussed. Using a study of neighborhoods in Dublin, Ireland and its suburbs we examine how professionals and the public view the places they live and connect these perspectives to the manner in which zoning has changed over the course of the twentieth century. Insights from these professionals and the public lead us to propose that planners, engineers and developers be expected to think more about the kinds of walkable village neighborhoods that people seem to be drawn to almost instinctively. We urge that zoning laws be re-purposed to enable the building of communities that people prefer to live in

Identifying High and Low Walkable Neighbourhoods Using Multi-disciplinary Walkability Criteria

Neighbourhood features contributing to the walkability (pedestrian friendliness) of a neighbourhood are diverse and depend on both its physical and social attributes. Earlier work in the Cleaner, Greener, Leaner (CGL) Study identified differences in opinion between professional stakeholder groups (planners, designers, engineers, public representatives, and public health and advocacy professionals) on what constitutes a walkable environment [1]. This diversity has implications for neighbourhood design and planning policy. The findings of a multi-disciplinary focus group study were used to generate a list of walkability criteria to select areas for a population study. In this study twenty areas were shortlisted and grouped under four categories: high walkable deprived, high walkable not deprived, low walkable deprived and low walkable not deprived. This paper presents the process undertaken to identify the study sites. International walkability research has favoured macro-scale objective geographic information systems (GIS) information to identify study areas [2]. While these macro scale attributes are important for walkability, alone they were considered insufficient for site selection by the CGL team as street characteristics were not considered and the attributes had a bias towards transportation walking. Also, indications from the focus group participants were that walkability is perceptual and therefore some resulting criteria were subjective, for example ‘a pleasant atmosphere contextual to area characteristics’ and therefore difficult to measure objectively. The CGL site selection process presented a number of challenges including limitations with available GIS information, unrepresentative neighbourhood boundaries on GIS datasets, and only one deprived neighbourhood identified as high walkable by the focus group participants. An investigation of the role of high and low walkable environments on resident’s behaviours and health can be used to inform future planning, transport, public health and neighbourhood design policies

Walkable Neighborhoods: Linkages Between Place, Health, and Happiness in Younger and Older Adults

Problem, research strategy, and findings: We examined whether living in a walkable neighborhood influenced the happiness of younger and older city residents. The data for this study came from a comprehensive household population survey of 1,064 adults living in 16 neighborhoods in Dublin City (Ireland) and its suburbs. We used multigroup structural equation modeling to analyze the direct and indirect effects of walkability on happiness, mediated by health, trust, and satisfaction with neighborhood appearance. We found living in a walkable neighborhood was directly linked to the happiness of people aged 36 to 45 (p¼.001) and, to a lesser extent, those aged 18 to 35 (p¼.07). For older adults, we found that walkable places mattered for happiness indirectly. Such built environments enhanced the likelihood that residents felt more healthy and more trusting of others, and this in turn affected the happiness of older people living in walkable neighborhoods. Takeaway for practice: We found that the way neighborhoods are planned and maintained mattered for happiness, health, and trust. Our findings suggest that mixed-use neighborhood designs that enable residents to shop and socialize within walking distance to their homes have direct and indirect effects on happiness. We call for an ongoing dialogue and evaluation of the way our urban and suburban neighborhoods are planned, designed, and developed, so that people can live in walkable places that better enable health and wellbeing

Characterizing the Causal Pathway From Childhood Adiposity to Right Heart Physiology and Pulmonary Circulation Using Lifecourse Mendelian Randomization

BACKGROUND: Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging. METHODS AND RESULTS: In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end-diastolic volume: β=0.24 [95% CI, 0.15-0.33]; P=3×10-7) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat-free mass and childhood height, respectively. CONCLUSIONS: Our findings suggest that, although childhood body size has a long-term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse

APC loss in breast cancer leads to doxorubicin resistance via STAT3 activation

Resistance to chemotherapy is one of the leading causes of death from breast cancer. We recently established that loss of Adenomatous Polyposis Coli (APC) in the Mouse Mammary Tumor Virus – Polyoma middle T (MMTV-PyMT) transgenic mouse model results in resistance to cisplatin or doxorubicin-induced apoptosis. Herein, we aim to establish the mechanism that is responsible for APC-mediated chemotherapeutic resistance. Our data demonstrate that MMTV-PyMT;ApcMin/+ cells have increased signal transducer and activator of transcription 3 (STAT3) activation. STAT3 can be constitutively activated in breast cancer, maintains the tumor initiating cell (TIC) population, and upregulates multidrug resistance protein 1 (MDR1). The activation of STAT3 in the MMTV-PyMT;ApcMin/+ model is independent of interleukin 6 (IL-6); however, enhanced EGFR expression in the MMTV-PyMT;ApcMin/+ cells may be responsible for the increased STAT3 activation. Inhibiting STAT3 with a small molecule inhibitor A69 in combination with doxorubicin, but not cisplatin, restores drug sensitivity. A69 also decreases doxorubicin enhanced MDR1 gene expression and the TIC population enhanced by loss of APC. In summary, these results have revealed the molecular mechanisms of APC loss in breast cancer that can guide future treatment plans to counteract chemotherapeutic resistance

The anaesthetic-ECT time interval with thiopentone—Impact on seizure quality

Background: The time between anaesthetic induction and ECT stimulus administration has been hypothesised to significantly impact ictal EEG quality. In this study, our aim was to examine the effect of the time interval between anaesthetic induction and the ECT stimulus for ictal seizure quality in ECT sessions utilising thiopentone anaesthesia. Methods: 413 EEG traces from 42 patients, collected retrospectively, were manually rated using a quantitative-qualitative structured rating scale (indices including seizure amplitude, regularity, post-ictal suppression and general seizure quality). Linear Mixed Effects Models were used to analyse the effect of the anaesthetic-ECT time interval on seizure quality indices, seizure duration and orientation scores after ECT, controlling for patient and ECT treatment factors. Results: The anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p < 0.05), with longer times producing higher quality seizures. Seizure duration and orientation scores after ECT were not significantly influenced by the anaesthetic-ECT time interval. Age, anaesthetic dose, ECT type and ECT treatment number also had a significant impact on measures of seizure quality (p < 0.05). Limitations: The effect of ventilation technique was not explicitly measured. Only manual ratings of ictal quality were analysed. Conclusions: The time between anaesthetic induction and ECT stimulus administration has a significant impact on the ictal EEG seizure quality observed, with thiopentone anaesthetic. These results are consistent with prior findings with propofol anaesthesia, and suggest a need for routine clinical monitoring of this time interval. This variable warrants consideration when interpreting ictal EEGs, which often informs subsequent dosing decisions

A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.</p