Towards humble geographies

This paper outlines the potential for a more “humble geography.” Most of us have been awed in some way by the world, humbled, but how often is that reflected in our work as geographers? As a thinking tool, “humble geographies” can combine insights and ethics from posthuman and feminist philosophies, participatory action research, and situated knowledges. Humility could helpfully contribute in debates seeking to improve geographic research practice. Humility, a quiet virtue, has potential to inspire change in the ways we relate with others and our institutions. Drawing on research experiences in the high Arctic archipelago of Svalbard, I give some examples of humble geographies in practice that raise questions about the ideal balance between authority and humility. How can we be humble in the face of rising pressures to sell ourselves and our research as highly impactful and important – in short, anything but humble? My aim is to open a discussion as to how we can helpfully inject more humility into our work.ESRC, Department of Geography and Earth Science, Aberystwyth Universit

Role of PARP1 and NAD+ Bioavailability in Base Excision and Single-Strand Break Repair

High-grade gliomas (HGGs) are malignant, highly metabolically active brain tumors. HGGs are associated with poor patient outcome, attributed to resistance to current therapies, with a survival rate between 12 to 15 months. Gliomas are highly complex tumors, making targeted therapy difficult, highlighting the need for novel approaches and new treatment options. In addition, a large percentage of HGGs are comprised of glioma stem cells (GSCs) that further contribute to therapeutic resistance. Notable characteristics of GSCs are a heightened DNA damage response (DDR) and elevated replication stress that could provide opportunities for therapeutic targeting. A notable feature of many glioma tumors that harbor mutations in isocitrate dehydrogenase isoforms 1 or 2 (IDH 1/2) mutations is reduced levels of the cellular metabolite nicotinamide adenine dinucleotide (NAD+). NAD+ is essential for cellular energy homeostasis and is responsible for the regulation of cellular processes such as fatty acid oxidation, glycolysis and the tricarboxylic acid cycle. IDH1/2 mutations are more sensitive to NAD+ depletion than wild-type cells and, therefore, may be a rational target for chemotherapeutics. In addition to a role in cellular metabolism, NAD+ serves as an important cofactor to poly-(ADP-ribose) polymerases (PARPs) and NAD-dependent deacetylases (Sirtuins) in chromatin remodeling. In our lab, we have found that GSCs have increased levels of the DDR protein Poly-(ADP-Ribose) polymerase 1 (PARP1) at both the mRNA and protein expression levels. However, we find that GSCs lack sufficient cellular NAD+ levels for xx robust PARP1 activation. PARP1 is involved in several DNA repair pathways that have evolved to repair specific types of DNA damage. Importantly, the NAD+ dependent enzymes PARP1 and PARP2, along with the sirtuin isoforms SIRT1 and SIRT6 (NAD+-dependent deacetylases), comprise a PARP-NAD+-SIRT axis that plays an essential role in the regulation and coordination of the base excision repair (BER) and single-stranded break repair (SSBR) pathways. The BER/SSBR pathway is responsible for repairing base damage and DNA single-strand breaks that result from both endogenous and exogenous sources, which are essential for genome maintenance. Defects in these pathways have been associated with the onset of cancer and other diseases. The activation of PARP1 is crucial to the cellular response to both base and SSB damage across the genome (referred to as canonical BER/SSBR) and the response to such lesions that impact replication associated BER/SSBR. The recruitment of and activation of PARP1 is essential for the relaxation of chromatin and recruitment of important BER/SSBR proteins to sites of DNA damage. However, central to that role is the hydrolysis of NAD+ by PARP1 to form poly-(ADP-ribose) (PAR) polymers. PARP1 covalently modifies itself and other proteins with PAR to facilitate and regulate DNA repair processes. We find that NAD+ is an important regulator of BER/SSBR as an essential substrate for PARP1. My hypothesis is that biological variation in cellular NAD+ levels modulate PARP1 activity, PAR metabolism and the PARP1-interactome to alter both canonical and replication-associated base excision and single-strand break repair. This variation impacts the efficacy of PARG inhibitors as a targeted cancer therapeutic option

Using DHS and MICS data to complement or replace NGO baseline health data: An exploratory study

Background: Non-government organizations (NGOs) spend substantial time and resources collecting baseline data in order to plan and implement health interventions with marginalized populations. Typically interviews with households, often mothers, take over an hour, placing a burden on the respondents. Meanwhile, estimates of numerous health and social indicators in many countries already exist in publicly available datasets, such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), and it is worth considering whether these could serve as estimates of baseline conditions. The objective of this study was to compare indicator estimates from non-governmental organizations (NGO) health projects' baseline reports with estimates calculated using the Demographic and Health Surveys (DHS) or the Multiple Indicator Cluster Surveys (MICS), matching for location, year, and season of data collection. / Methods: We extracted estimates of 129 indicators from 46 NGO baseline reports, 25 DHS datasets and three MICS datasets, generating 1,996 pairs of matched DHS/MICS and NGO indicators. We subtracted NGO from DHS/MICS estimates to yield difference and absolute difference, exploring differences by indicator. We partitioned variance of the differences by geographical level, year, and season using ANOVA. / Results: Differences between NGO and DHS/MICS estimates were large for many indicators but 33% fell within 5% of one another. Differences were smaller for indicators with prevalence 85%. Difference between estimates increased with increasing year and geographical level differences. However, <1% of the variance of the differences was explained by year, geographical level, and season. / Conclusions: There are situations where publicly available data could complement NGO baseline survey data, most importantly when the NGO has tolerance for estimates of low or unknown accuracy

Equity implications of rice fortification: a modelling study from Nepal.

OBJECTIVE: To model the potential impact and equity impact of fortifying rice on nutritional adequacy of different subpopulations in Nepal. DESIGN: Using 24-h dietary recall data and a household consumption survey, we estimated: rice intakes; probability of adequacy (PA) of eight micronutrients commonly fortified in rice (vitamin A, niacin (B3), pyridoxine (B6), cobalamin (B12), thiamin (B1), folate (B9), Fe and Zn) plus riboflavin (B2), vitamin C and Ca and mean probability of adequacy (MPA) of these micronutrients. We modelled: no fortification; fortification of purchased rice, averaged across all households and in rice-buying households only. We compared adequacy increases between population subgroups. SETTING: (i) Dhanusha and Mahottari districts of Nepal (24-h recall) and (ii) all agro-ecological zones of Nepal (consumption data). PARTICIPANTS: (i) Pregnant women (n 128), mothers-in-law and male household heads; (ii) households (n 4360). RESULTS: Unfortified diets were especially inadequate in vitamins B12, A, B9, Zn and Fe. Fortification of purchased rice in rice-purchasing households increased PA > 0·9 for thiamin, niacin, B6, folate and Zn, but B12 and Fe remained inadequate even after fortification (PA range 0·3-0·9). Pregnant women's increases exceeded men's for thiamin, niacin, B6, folate and MPA; men had larger gains in vitamin A, B12 and Zn. Adequacy improved more in the hills (coefficient 0·08 (95 % CI 0·05, 0·10)) and mountains (coefficient 0·07 (95 % CI 0·01, 0·14)) but less in rural areas (coefficient -0·05 (95 % CI -0·09, -0·01)). CONCLUSIONS: Consumption of purchased fortified rice improves adequacy and gender equity of nutrient intake, especially in non-rice-growing areas

A feminist vision for transformative change to disaster risk reduction policies and practices

Gender has received increased attention in disaster risk reduction (DRR) policies and practices over the past three decades. However, a critical analysis raises a number of questions: has the attention to gender brought transformative change to the lives of people, especially women and sexual minorities in all their diversity? To what extent has the inclusion of a gender perspective in DRR challenged the root causes of vulnerability and marginalization? Do the current gender sensitive DRR policies and practices have transformative potential? In this paper, we explore some of these questions with particular reference to the recent Disaster Risk Reduction and Management (DRRM) Act 2017 and current DRR practices in Nepal in which gender has been included. We present findings from three research projects, undertaken between 2016 and 2019 in six locations in Nepal. These comprised 105 individual interviews, 11 group interviews and 3 focus group discussions (FGDs) with internally displaced women; pregnant and newly delivered women; health and community workers; policy makers, political leaders and organisations working on DRR. We argue that, despite increased attention to gender, current DRR policies and practices do little to challenge existing, unequal social and institutional structures; instead, they accommodate the gender status quo. We suggest that in order for transformative social change to occur, we require a transformative vision; one that allows us to see the biases and problems within the current DRR policies and practices and allows us to imagine our future differently. A feminist vision offers that possibility

Independent associations of women's age at marriage and first pregnancy with their height in rural lowland Nepal

OBJECTIVES: In many South Asian communities, the majority of women are married during adolescence and reproduce before 20 years. Early reproduction may adversely affect maternal nutrition and linear growth, however whether early marriage has similar effects is unknown. Shorter women might also be preferentially chosen for earlier marriage. We hypothesized that early marriage and early pregnancy may each be associated with women's shorter height, independent of any selection effects. MATERIALS AND METHODS: We analyzed cross-sectional data on 7,146 women aged 20-30 years from rural lowland Nepal. Linear regression models tested associations of early marriage and early reproduction with height, adjusting for women's education and husbands' characteristics (education and wealth) that might index preferential selection of short young women for marriage. RESULTS: Median ages at marriage and first pregnancy were 15 and 18 years, respectively, with 20% pregnant <16 years. Both early marriage and early pregnancy were independently associated with shorter stature, accounting for a decrement of 1.4 cm, which decreased to 1 cm after adjusting for women's education. Effects of early marriage and reproduction persisted after adjusting for the tendency of poorer and less educated men to marry young and short women, indicating a role for social selection. DISCUSSION: The decrements in height associated with early marriage and reproduction are indicative of broader adverse effects on maternal metabolism during a "critical period" of growth and maturation in the life-course of women. Although the magnitudes of effect are relatively small, they affect large numbers of women in this population