The National Dialogue on the Quadrennial Homeland Security Review

Six years after its creation, the Department of Homeland Security (DHS) undertook the first Quadrennial Homeland Security Review (QHSR) to inform the design and implementation of actions to ensure the safety of the United States and its citizens. This review, mandated by the Implementing the 9/11 Commission Recommendations Act of 2007, represents the first comprehensive examination of the homeland security strategy of the nation. The QHSR includes recommendations addressing the long-term strategy and priorities of the nation for homeland security and guidance on the programs, assets, capabilities, budget, policies, and authorities of the department.Rather than set policy internally and implement it in a top-down fashion, DHS undertook the QHSR in a new and innovative way by engaging tens of thousands of stakeholders and soliciting their ideas and comments at the outset of the process. Through a series of three-week-long, web-based discussions, stakeholders reviewed materials developed by DHS study groups, submitted and discussed their own ideas and priorities, and rated or "tagged" others' feedback to surface the most relevant ideas and important themes deserving further consideration.Key FindingsThe recommendations included: (1) DHS should enhance its capacity for coordinating stakeholder engagement and consultation efforts across its component agencies, (2) DHS and other agencies should create special procurement and contracting guidance for acquisitions that involve creating or hosting such web-based engagement platforms as the National Dialogue, and (3) DHS should begin future stakeholder engagements by crafting quantitative metrics or indicators to measure such outcomes as transparency, community-building, and capacity

Gene transfer and expression in human neutrophils. The phox homology domain of p47(phox )translocates to the plasma membrane but not to the membrane of mature phagosomes

BACKGROUND: Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. RESULTS: Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX) domain of p47(phox )localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47(phox), is translocated to the membrane of mature phagosomes. CONCLUSION: We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils

Microbial impacts on 99mTc migration through sandstone under highly alkaline conditions relevant to radioactive waste disposal

Geological disposal of intermediate level radioactive waste in the UK is planned to involve the use of cementitious materials, facilitating the formation of an alkali-disturbed zone within the host rock. The biogeochemical processes that will occur in this environment, and the extent to which they will impact on radionuclide migration, are currently poorly understood. This study investigates the impact of biogeochemical processes on the mobility of the radionuclide technetium, in column experiments designed to be representative of aspects of the alkali-disturbed zone. Results indicate that microbial processes were capable of inhibiting 99mTc migration through columns, and X-ray radiography demonstrated that extensive physical changes had occurred to the material within columns where microbiological activity had been stimulated. The utilisation of organic acids under highly alkaline conditions, generating H2 and CO2, may represent a mechanism by which microbial processes may alter the hydraulic conductivity of a geological environment. Column sediments were dominated by obligately alkaliphilic H2-oxidising bacteria, suggesting that the enrichment of these bacteria may have occurred as a result of H2 generation during organic acid metabolism. The results from these experiments show that microorganisms are able to carry out a number of processes under highly alkaline conditions that could potentially impact on the properties of the host rock surrounding a geological disposal facility for intermediate level radioactive waste

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PurposeWomen with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).MethodsPatients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method.ResultsOf the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8).ConclusionLRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy

DHA supplementation during pregnancy does not reduce BMI or body fat mass in children: follow-up of the DHA to Optimize Mother Infant Outcome randomized controlled trial

First published March 30, 2016The omega-3 (n-3) long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) has proven effective at reducing fat storage in animal studies. However, a systematic review of human trials showed a lack of quality data to support or refute this hypothesis.We sought to determine whether maternal DHA supplementation during the second half of pregnancy results in a lower body mass index (BMI) and percentage of body fat in children.We conducted a follow-up at 3 and 5 y of age of children who were born to mothers enrolled in the DOMInO (DHA to Optimize Mother Infant Outcome) double-blind, randomized controlled trial, in which women with a singleton pregnancy were provided with DHA-rich fish-oil capsules (800 mg DHA/d) or vegetable-oil capsules (control group) in the second half of pregnancy. Primary outcomes were the BMIzscore and percentage of body fat at 3 and 5 y of age. Potential interactions between prenatal DHA and the peroxisome proliferator-activated receptor-γ (PPARγ) genotype as a measure of the genetic predisposition to obesity were investigated.A total of 1614 children were eligible for the follow-up. Parent or caregiver consent was obtained for 1531 children (95%), and these children were included in the analysis. BMIzscores and percentages of body fat of children in the DHA group did not differ from those of children in the control group at either 3 y of age [BMIzscore adjusted mean difference: 0.03 (95% CI: -0.07, 0.13;P= 0.61); percentage of body fat adjusted mean difference: -0.26 (95% CI: -0.99, 0.46;P= 0.47)] or 5 y of age [BMIzscore adjusted mean difference: 0.02 (95% CI: -0.08, 0.12;P= 0.66); percentage of body fat adjusted mean difference: 0.11 (95% CI: -0.60, 0.82;P= 0.75)]. No treatment effects were modified by thePPARγgenotype of the child.Independent of a genetic predisposition to obesity, maternal intake of DHA-rich fish oil during the second half of pregnancy does not affect the growth or body composition of children at 3 or 5 y of age. This trial was registered atwww.anzctr.org.auas ACTRN1260500056906 and ACTRN12611001127998.Beverly S Muhlhausler, Lisa N Yelland, Robyn McDermott, Linda Tapsell, Andrew McPhee, Robert A Gibson, and Maria Makride

Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer

No single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)–positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab

Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer

Trastuzumab is life-saving but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. Here we report the low cardiac toxicity of a non-anthracycline and trastuzumab based treatment for patients with early stage HER2-positive breast cancer (BCA)

Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial)

Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50% of all premenopausal recipients [1]

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29