Do Demographic Profiles of Listed and Unlisted Households Differ? Results of a Nationwide Telephone Survey

A growing number of households are not reachable through traditional directory-based samples, which can have important implications for the representativeness of telephone surveys. The current study aims to investigate the demographic differences between households which have their telephone numbers listed or not listed in the Australian White Pages telephone directory. A total of 5,023 eligible Australian residents who were currently in paid employment participated in this study. Each respondent’s telephone number was individually matched to the residential White Pages to determine its listed status, and demographic variables were compared between those with a listed and unlisted telephone number. Those with an unlisted number were significantly more likely to be younger, to have been born in a country outside of Australia, and to live in a lower socioeconomic area than those who were listed in the White Pages. These demographic differences should be considered when undertaking telephone surveys using a White Pages sample

Penalties and Rewards for Fair Learning in Paired Kidney Exchange Programs

A kidney exchange program, also called a kidney paired donation program, can be viewed as a repeated, dynamic trading and allocation mechanism. This suggests that a dynamic algorithm for transplant exchange selection may have superior performance in comparison to the repeated use of a static algorithm. We confirm this hypothesis using a full scale simulation of the Canadian Kidney Paired Donation Program: learning algorithms, that attempt to learn optimal patient-donor weights in advance via dynamic simulations, do lead to improved outcomes. Specifically, our learning algorithms, designed with the objective of fairness (that is, equity in terms of transplant accessibility across cPRA groups), also lead to an increased number of transplants and shorter average waiting times. Indeed, our highest performing learning algorithm improves egalitarian fairness by 10% whilst also increasing the number of transplants by 6% and decreasing waiting times by 24%. However, our main result is much more surprising. We find that the most critical factor in determining the performance of a kidney exchange program is not the judicious assignment of positive weights (rewards) to patient-donor pairs. Rather, the key factor in increasing the number of transplants, decreasing waiting times and improving group fairness is the judicious assignment of a negative weight (penalty) to the small number of non-directed donors in the kidney exchange program.Comment: Shorter version accepted in WINE 202

Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers

The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB

Interventions to promote cycling: systematic review

Objectives To determine what interventions are effective in promoting cycling, the size of the effects of interventions, and evidence of any associated benefits on overall physical activity or anthropometric measures

Age-related differences in breast cancer mortality according to race/ethnicity, insurance, and socioeconomic status.

BackgroundWe assessed breast cancer mortality in older versus younger women according to race/ethnicity, neighborhood socioeconomic status (nSES), and health insurance status.MethodsThe study included female breast cancer cases 18 years of age and older, diagnosed between 2005 and 2015 in the California Cancer Registry. Multivariable Cox proportional hazards modeling was used to generate hazard ratios (HR) of breast cancer specific deaths and 95% confidence intervals (CI) for older (60+ years) versus younger (< 60 years) patients separately by race/ethnicity, nSES, and health insurance status.ResultsRisk of dying from breast cancer was higher in older than younger patients after multivariable adjustment, which varied in magnitude by race/ethnicity (P-interaction< 0.0001). Comparing older to younger patients, higher mortality differences were shown for non-Hispanic White (HR = 1.43; 95% CI, 1.36-1.51) and Hispanic women (HR = 1.37; 95% CI, 1.26-1.50) and lower differences for non-Hispanic Blacks (HR = 1.17; 95% CI, 1.04-1.31) and Asians/Pacific Islanders (HR = 1.15; 95% CI, 1.02-1.31). HRs comparing older to younger patients varied by insurance status (P-interaction< 0.0001), with largest mortality differences observed for privately insured women (HR = 1.51; 95% CI, 1.43-1.59) and lowest in Medicaid/military/other public insurance (HR = 1.18; 95% CI, 1.10-1.26). No age differences were shown for uninsured women. HRs comparing older to younger patients were similar across nSES strata.ConclusionOur results provide evidence for the continued disparity in Black-White breast cancer mortality, which is magnified in younger women. Moreover, insurance status continues to play a role in breast cancer mortality, with uninsured women having the highest risk for breast cancer death, regardless of age

Vulvar Cancer Outcomes in Women Living with HIV in the Age of Anti-Retroviral Therapy

https://openworks.mdanderson.org/sumexp23/1123/thumbnail.jp

New mutations in flagellar motors identified by whole genome sequencing in Chlamydomonas

BACKGROUND: The building of a cilium or flagellum requires molecular motors and associated proteins that allow the relocation of proteins from the cell body to the distal end and the return of proteins to the cell body in a process termed intraflagellar transport (IFT). IFT trains are carried out by kinesin and back to the cell body by dynein. METHODS: We used whole genome sequencing to identify the causative mutations for two temperature-sensitive flagellar assembly mutants in Chlamydomonas and validated the changes using reversion analysis. We examined the effect of these mutations on the localization of IFT81, an IFT complex B protein, the cytoplasmic dynein heavy chain (DHC1b), and the dynein light intermediate chain (D1bLIC). RESULTS: The strains, fla18 and fla24, have mutations in kinesin-2 and cytoplasmic dynein, respectively. The fla18 mutation alters the same glutamic acid (E(24)G) mutated in the fla10-14 allele (E(24)K). The fla18 strain loses flagella at 32?C more rapidly than the E(24)K allele but less rapidly than the fla10-1 allele. The fla18 mutant loses its flagella by detachment rather than by shortening. The fla24 mutation falls in cytoplasmic dynein and changes a completely conserved amino acid (L(3243)P) in an alpha helix in the AAA5 domain. The fla24 mutant loses its flagella by shortening within 6 hours at 32?C. DHC1b protein is reduced by 18-fold and D1bLIC is reduced by 16-fold at 21?C compared to wild-type cells. We identified two pseudorevertants (L(3243)S and L(3243)R), which remain flagellated at 32?C. Although fla24 cells assemble full-length flagella at 21?C, IFT81 protein localization is dramatically altered. Instead of localizing at the basal body and along the flagella, IFT81 is concentrated at the proximal end of the flagella. The pseudorevertants show wild-type IFT81 localization at 21?C, but proximal end localization of IFT81 at 32?C. CONCLUSIONS: The change in the AAA5 domain of the cytoplasmic dynein in fla24 may block the recycling of IFT trains after retrograde transport. It is clear that different alleles in the flagellar motors reveal different functions and roles. Multiple alleles will be important for understanding structure-function relationships

'Functional' inspiratory and core muscle training enhances running performance and economy.

We compared the effects of two 6-week high-intensity interval training interventions. Under the control condition (CON), only interval training was undertaken, whilst under the intervention condition (ICT), interval training sessions were followed immediately by core training, which was combined with simultaneous inspiratory muscle training - 'functional' IMT. Sixteen recreational runners were allocated to either ICT or CON groups. Prior to the intervention phase, both groups undertook a 4-week programme of 'foundation' IMT to control for the known ergogenic effect of IMT [30 inspiratory efforts at 50% maximal static inspiratory pressure (P0) per set, 2 sets.d, 6 d.wk]. The subsequent 6-week interval running training phase, consisted of 3-4 sessions.wk. In addition, the ICT group undertook four inspiratory-loaded core exercises [10 repetitions.set, 2 sets.d, inspiratory load set at 50% post-IMT P0] immediately after each interval training session. The CON group received neither core training nor functional IMT. Following the intervention phase, global inspiratory and core muscle functions increased in both groups (P<0.05), as evidenced by P0 and a sport-specific endurance plank test performance (SEPT), respectively. Compared to CON, the ICT group showed larger improvements in SEPT, running economy at the speed of the OBLA, and 1-hr running performance (3.04% vs 1.57%, P<0.05). The changes in these variables were inter-individually correlated (r≥0.57, n=16, P<0.05). Such findings suggest that the addition of inspiratory-loaded core conditioning into a high-intensity interval training program augments the influence of the interval program upon endurance running performance, and that this may be underpinned by an improvement in running economy