representative sample of rural Bangladeshi households. • With the onset of the pandemic, combined with the lockdown restrictions imposed from March through May 2020, moderate and severe food insecurity tripled to 45 percent. This was likely driven by income losses and difficulties accessing food because of shop closures. • By January 2021, the proportion of moderately or severely food insecure households had largely returned to pre-pandemic levels. The September-October 2021 survey showed no meaningful further change in the prevalence of moderate or severe food insecurity despite the strict national lockdown imposed in July-August 2021. • A different picture emerges when we include the prevalence of mild food insecurity. The proportion of households reporting any food insecurity (mild, moderate or severe) increased from the pre-pandemic average of 45.7 percent to 87.8 percent in June 2020, before declining to 70.9 percent in January 2021 and 68 percent in September-October 2021. Dimensions of food insecurity that include consuming less diverse diets, being unable to eat healthy/nutritious food, and above all, being worried about not having enough food increased dramatically at the start of the pandemic and have remained elevated. • Pre-pandemic, the majority of rural households in our sample were fully food secure; 18 months after the onset of the pandemic only 32 percent report no forms of food insecurity. • In the immediate months after the outbreak (June 2020), many rural households coped by reducing expenditures on non-food goods, electricity and other utilities, and health-related items. The use of these forms of coping mechanisms has subsequently declined. However, the proportion of rural households that purchased food on credit (69 percent in June 2020) has barely changed and in all surveys fielded since the start of the pandemic, more than half of surveyed households have borrowed money to buy food. The continued use of savings and the ongoing use of credit to purchase food is consistent with the elevated levels of worry about not having enough food. • A substantial share of rural households reported receiving cash or in-kind safety net support during the pandemic, mostly from government sources. • Continued and expanded support from safety nets may be important, as many rural households face ongoing food insecurity and are using unsustainable coping strategies.

The COVID-19 pandemic compelled the Government of Bangladesh to impose policy measures to stop the spread of the virus. These efforts were critical for public health, but have led to serious disruptions in the economy and livelihoods. To document the experiences of Bangladeshi households during this time, the International Food Policy Research Institute (IFPRI) and Cornell University conducted two rounds of socioeconomic phone surveys in rural areas of Bangladesh in June 2020 and in January 2021, and benchmarked them against data from in-person interviews carried out on the same households in 2019. Together, these surveys have tracked the experiences of Bangladeshi households in terms of unemployment, income loss, food insecurity, and coping mechanisms during the COVID-19 pandemic.

Targeting DNA repair enzymes has attracted much attention in recent years to overcome the therapeutic resistance in cancer therapy. Inhibition of DNA repair enzymes can be used to make cancer cells sensitive to the DNA damaging effect of ionizing radiation or chemotherapy. In addition, the downregulation or mutation of specific DNA repair enzymes and/or tumor suppressor proteins in cancer cells can make them particularly more sensitive to the inhibition of DNA repair, a process known as "synthetic lethality". Human polynucleotide kinase/phosphatase (PNKP) is a bifunctional DNA repair enzyme which phosphorylates DNA 5′-termini and dephosphorylates DNA 3′-termini that processes the ligation of damaged DNA termini. The inhibition of PNKP can make cancer cells more sensitive to DNA damage by ionizing radiation or Topoisomerase I inhibitors. Through siRNA library screening, a synthetic lethal partnership between loss of PNKP and tumor suppressor Phosphatase and TENsin homolog deleted on chromosome 10 (PTEN). This inspired development of several small molecule inhibitors of PNKP. These newly synthesized PNKP inhibitors are not water-soluble, therefore not injectable. My research aim was to develop delivery systems at nanometer size range that can target a small molecule inhibitor of PNKP, known as A83B4C63 to the tumor while reducing their access to normal tissues. The nanocarriers were fabricated from self-associating block copolymers based on poly(ethylene oxide) (PEO) and poly(caprolactone) (PEO-PCL) or a-benzyl carboxylate substituted poly(caprolactone), abbreviated as PEO-PBCL. The developed nanocarriers were used for the encapsulation of A83B4C63 alone or with the active metabolite of irinotecan, i.e., SN-38. The developed formulations were characterized for their average diameter, polydispersity, morphology, loading properties, release profiles as well as sensitization of cancer cells to SN38 and/or ionizing radiation both in vitro and in vivo. To identify the binding affinity between intracellular PNKP and A83B4C63, a novel biophysical assay known as Cellular Thermal Shift Assay (CETSA) was developed and used. Maximum tolerated dose of A83B4C63 formulated with the aid of Cremophor EL:Ethanol (CE) and nanocarrier formulations was investigated in healthy CD-1 mice. The performed biochemical toxicity and immune histochemical experiments demonstrated that the intravenous (IV) administration of A83B4C63 in nanocarriers or CE form was not toxic up to the maximum examined dose of 50 mg/kg dose, although the nanocarrier injection was tolerated better by mice. The in vivo anticancer activity of the above formulations was also determined in colorectal cancer xenografts in mice either in PTEN negative model as monotherapy or in wild type model in combination with radiation therapy using the Small Animal Radiation Research Platform (SARRP). The results provided evidence for the anticancer activity of nanocarrier formulation of A83B4C63 as monotherapy in PTEN deficient HCT116 xenografts in mice. Inhibition of tumor growth was also observed as a result of combination of A83B4C63 nanocarriers with radiation therapy in wild type PTEN+ HCT116 xenografts in mice. This contrasted with the CE formulation of the PNKP inhibitor that did not show any activity, in vivo. The superior activity of the nano-formulation of A83B4C63 over CE formulation was attributed to the enhanced distribution of the drug to tumor site by its nanocarrier. A synergistic effect was also observed when nanocarriers of A83B4C63 were combined with SN-38 or its nano-formulation in CRC models, in vitro. The outcomes of this thesis have demonstrated the great feasibility of nano-delivery of a novel inhibitor of DNA repair for CRC therapy either as a single drug in PTEN deficient form or in combination with DNA damaging therapeutics.