Form-Based Codes, Design Guidelines and Placemaking: The Case of Hayward, Ca.

Throughout history planning codes and standards have been used to regulate the built environment for health, power, order, and economic reasons. More recently, in the urban design and planning field, planning codes and standards have emerged to become tools in the process of “placemaking”. The concept of placemaking builds from the desire of humans to create places, not spaces, which are unique, attractive, identifiable, and memorable. It is a concept that is comprised of visual and social components, recognizing the need for both in the creation of successful places. In the field of urban design and planning, form-based codes (FBCs) and design guidelines have emerged to become two types of planning tools used in the process of placemaking. This study explores the relationship between FBCs, design guidelines, and placemaking, investigating it through an extensive literature review, and then in the context of the case of Hayward, California through an update of the City’s Downtown design requirements and guidelines. To frame the update of the Hayward’s Downtown design requirements and guidelines this study used an exploratory methodology that combined quantitative and qualitative methods. Archival research was conducted to provide a historical narrative of the City and the Downtown area and a documents analysis was conducted to reveal information about existing Downtown policies and programs. Community participation through the crowdsourcing platform of MindMixer was used to collect community input and feedback about concepts of place in Downtown. The data analysis and findings from these methods were combined with findings from the literature review to formulate recommendations that were used in the update of Hayward’s Downtown design requirements and guidelines document. Keywords

Minimal Permutations and 2-Regular Skew Tableaux

Bouvel and Pergola introduced the notion of minimal permutations in the study of the whole genome duplication-random loss model for genome rearrangements. Let $\mathcal{F}_d(n)$ denote the set of minimal permutations of length $n$ with $d$ descents, and let $f_d(n)= |\mathcal{F}_d(n)|$. They derived that $f_{n-2}(n)=2^{n}-(n-1)n-2$ and $f_n(2n)=C_n$, where $C_n$ is the $n$-th Catalan number. Mansour and Yan proved that $f_{n+1}(2n+1)=2^{n-2}nC_{n+1}$. In this paper, we consider the problem of counting minimal permutations in $\mathcal{F}_d(n)$ with a prescribed set of ascents. We show that such structures are in one-to-one correspondence with a class of skew Young tableaux, which we call $2$-regular skew tableaux. Using the determinantal formula for the number of skew Young tableaux of a given shape, we find an explicit formula for $f_{n-3}(n)$. Furthermore, by using the Knuth equivalence, we give a combinatorial interpretation of a formula for a refinement of the number $f_{n+1}(2n+1)$.Comment: 19 page

Balancing Early Antibiotic Administration and Stewardship in Sepsis

Presented at the 3rd Annual Sepsis Symposiu

Fluorescence in situ hybridization (FISH) and risk factors for non-Hodgkin lymphoma (NHL) subtypes defined by t(14;18) translocations and bcl-2 expression

In hopes of increasing etiologic specificity of non-Hodgkin lymphoma (NHL), we defined NHL tumors by acquired chromosomal translocations involving the immunoglobulin heavy chain (any IGH), t(14;18), t(8;14) and BCL6 translocations using fluorescence in situ hybridization (FISH) assays of archival paraffin-embedded tumor blocks. Translocations were identified in samples from over 200 unselected NHL cases originally enrolled in the National Cancer Institute's Factors Affecting Rural Men (FARM) study (1981-1984). We re-evaluated reported associations between tobacco exposures and t(14;18)-NHL case-subtypes that were previously defined based on polymerase chain reaction (PCR) assays. We also evaluated bcl-2 protein expression based on immunohistochemistry. t(14;18)-FISH case-subtypes were compared with t(14;18)-PCR case-subtypes by frequency according to histologic subtype and bcl-2 status. Case:control associations were estimated using multivariate polytomous logistic regression for t(14;18)-NHL and factors including tobacco use, family history of hemolymphatic cancer, and hair dye use. The expectation-maximization (EM) algorithm was applied to case:control models to reduce bias due to missing case-subtype data. BCL6 translocations, t(8;14), and other IGH translocations were uncommon in the study population. t(14;18) was identified in 53% of cases, including 39% of diffuse large cell lymphomas (26 of 66 cases) and 81% of follicular lymphomas (35 of 43 cases). FISH assays detected almost twice as many t(14;18)-positive follicular lymphomas as PCR assays (44%) run on the same samples. The majority of cases expressed bcl-2, including 87% of t(14;18)-positive cases and 58% of t(14;18)-negative cases. Adjusting for age, state, and proxy status, t(14;18)-negative NHL was associated with any tobacco use (OR=1.98, 95% CI=1.09-3.59) and cigarette smoking, without evidence of a linear dose-response with increasing pack-years or intensity of smoking. In contrast, tobacco and cigarette use were not clearly associated with t(14;18)-positive NHL or with bcl-2 case-subtypes. Our results support the use of FISH assays of archival samples to identify t(14;18)-NHL case-subtypes. The association between t(14;18)-negative NHL and cigarette smoking was unexpected given previous evidence of associations between smoking and follicular lymphoma (which is largely t(14;18)-positive). Additional molecular characterization of t(14;18)-negative cases may clarify whether the association between tobacco use and t(14;18)-negative NHL was causal versus an artifact of chance or bias

Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping.

Tissue clearing methods promise to provide exquisite three-dimensional imaging information; however, there is a need for simplified methods for lower resource settings and for non-fluorescence based phenotyping to enable light microscopic imaging modalities. Here we describe the simplified CLARITY method (SCM) for tissue clearing that preserves epitopes of interest. We imaged the resulting tissues using light sheet microscopy to generate rapid 3D reconstructions of entire tissues and organs. In addition, to enable clearing and 3D tissue imaging with light microscopy methods, we developed a colorimetric, non-fluorescent method for specifically labeling cleared tissues based on horseradish peroxidase conversion of diaminobenzidine to a colored insoluble product. The methods we describe here are portable and can be accomplished at low cost, and can allow light microscopic imaging of cleared tissues, thus enabling tissue clearing and imaging in a wide variety of settings

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57− PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57− PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.This work was supported by National Health and Medical Research Council (Australia) program grants APP1016953 and APP427620 (CGV, CCG, SGT, MCC)

Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3

Hyper–immunoglobulin E syndrome (HIES) is a primary immune deficiency characterized by abnormal and devastating susceptibility to a narrow spectrum of infections, most commonly Staphylococcus aureus and Candida albicans. Recent investigations have identified mutations in STAT3 in the majority of HIES patients studied. Despite the identification of the genetic cause of HIES, the mechanisms underlying the pathological features of this disease remain to be elucidated. Here, we demonstrate a failure of CD4+ T cells harboring heterozygous STAT3 mutations to generate interleukin 17–secreting (i.e., T helper [Th]17) cells in vivo and in vitro due to a failure to express sufficient levels of the Th17-specific transcriptional regulator retinoid-related orphan receptor γt. Because Th17 cells are enriched for cells with specificities against fungal antigens, our results may explain the pattern of infection susceptibility characteristic of patients with HIES. Furthermore, they underscore the importance of Th17 responses in normal host defense against the common pathogens S. aureus and C. albicans

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed