Measuring speed of vessels operating around endangered southern resident killer whales (Orcinus orca) in Salish Sea critical habitat.

Motorized vessels are a major source of anthropogenic noise and can have adverse effects on species relying on sound for communication and feeding. Monitoring noise levels received by endangered southern resident killer whales (SRKWs) requires knowing the number, distance, and speed of surrounding vessels, including small boats that do not have Automatic Identification Systems (AIS). A method for estimating their speed is required to predict received noise levels and compliance with vessel regulations. We compared theodolite and photogrammetry methods to estimate the number, distance, and speed of vessels in SRKW Salish Sea summertime critical habitat. By treating AIS as "truth", we found photogrammetry-derived ranges and speeds were more variable than theodolite estimates. Error in photogrammetry-derived speeds increased with range. Overall, we found time saved in the field using photogrammetry was more than offset by long analysis time. Theodolite data were relatively easy to collect, and produced accurate and precise results.

Evaluation of the Effectiveness and Safety of Direct Oral Anticoagulants in Elderly Patients With Nonvalvular Atrial Fibrillation Who Are Not Candidates for Warfarin in Real-World Setting.

ABSTRACT: Limited literature has established the role of direct oral anticoagulants (DOAC) for elderly patients with nonvalvular atrial fibrillation who are unsuited for warfarin. Therefore, the objectives of this study were to assess the effectiveness and safety of DOAC use in this vulnerable patient population. This was a retrospective propensity score matching cohort study. Among all patients aged 75+ years who were not candidates for warfarin, we matched those who initiated DOAC between September 2017 and September 2018 with those who did not receive DOAC or warfarin in a 1:1 ratio. Effectiveness outcome was a composite measure of stroke, transient ischemic attack, and pulmonary embolism. Safety outcome was a composite measure of non-trauma-related intracranial hemorrhage and gastrointestinal bleed. Unless patients died or lost membership, follow-up period for the effectiveness outcome was until the end of 2019, whereas the safety outcome was for a period up to 1 year. Conditional logistic regression was used to analyze both outcomes. We identified 7818 patients who met the inclusion criteria and started DOAC, which matched to 7818 patients who did not receive anticoagulants. The mean age was 82.3 ± 5.1 years, and 51.5% male. The DOAC group had a lower hazard ratio of 0.37 (confidence interval, 0.24-0.57; P < 0.01) for composite effectiveness outcomes, whereas no difference in the composite safety outcome (hazard ratio, 0.91; confidence interval, 0.65-1.25; P = 0.55) when compared with matched control. In conclusion, DOAC was found to be effective in preventing thromboembolic events in patients aged 75+ years with nonvalvular atrial fibrillation who were not eligible for warfarin.

Behavioural responses of wild Pacific salmon and herring to boat noise.

There is growing concern about impacts of ship and small boat noise on marine wildlife. Few studies have quantified impacts of anthropogenic noise on ecologically, economically, and culturally important fish. We conducted open net pen experiments to measure Pacific herring (Clupea pallasii) and juvenile salmon (pink, Oncorhynchus gorbuscha, and chum, Oncorhynchus keta) behavioural response to noise generated by three boats travelling at different speeds. Dose-response curves for herring and salmon estimated 50% probability of eliciting a response at broadband received levels of 123 and 140 dB (re 1 µPa), respectively. Composite responses (yes/no behaviour change) were evaluated. Both genera spent more time exhibiting behaviours consistent with anti-predator response during boat passings. Repeated elicitation of vigilance or anti-predatory responses could result in increased energy expenditure or decreased foraging. These experiments form an important step toward assessing population-level consequences of noise, and its ecological costs and benefits to predators and prey.

Securitizing HIV/AIDS: a game changer in state-societal relations in China?

BACKGROUND: China has experienced unprecedented economic growth since the 1980s. Despite this impressive economic development, this growth exists side by side with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and severe acute respiratory syndrome (SARS) crises and the persisting deficiencies in public health provision in China. Acknowledging the prevailing health problems, the Chinese government has encouraged the development of health non-governmental organizations (NGOs) to respond to the health challenges and address the gaps in public health provision of the government. HIV/AIDS-focused NGOs have been perceived as the most outstanding civil society group developed in China. Considering the low priority of health policies since the economic reform, the limitation of the "third sector" activity permitted in authoritarian China, together with the political sensitivity of the HIV/AIDS problem in the country, this article aims to explain the proliferation of HIV/AIDS-focused NGOs in China with the usage of the securitization framework in the field of international relations (IR). METHODS: The research that underpins this article is based on a desk-based literature review as well as in-depth field interviews with individuals working in HIV/AIDS-focused NGOs in China. Face-to-face interviews for this research were conducted between January and May in 2011, and between December 2016 and January 2017, in China. Discourse analysis was in particular employed in the study of the security-threat framing process (securitization) of HIV/AIDS in China. RESULTS: This article argues that the proliferation of HIV/AIDS-related NGOs in China is largely attributed to the normative and technical effects of HIV/AIDS securitization ushered in by the United Nations Security Council (UNSC) and supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria (hereinafter Global Fund) observed in China. Despite depicting a positive scenario, the development of HIV/AIDS-focused NGOs in China generated by the international securitization efforts is largely limited. An internal and external factor was identified to verify the argument, namely (1) the reduction of international financial commitments, as well as (2) the fragmentation of HIV/AIDS-focused NGO community in China. CONCLUSIONS: This article shows that international securitization weakened with the rise of Chinese commitment on HIV/AIDS interventions. In other words, HIV/AIDS-related responses delivered by the national government are no longer checked by the global mechanism of HIV/AIDS; thus it is unclear whether these NGOs would remain of interest as partners for the government. The fragmentation of the HIV/AIDS community would further hinder the development, preventing from NGOs with the same interest forming alliances to call for changes in current political environment. Such restriction on the concerted efforts of HIV/AIDS-related NGOs in China would make achievement of the Sustainable Development Goals (SDGs) to foster stronger partnerships between the government and civil society difficult, which in turn hindering the realization of ending HIV/AIDS in the world by 2030.

Managing Nonoperable Intracranial Bleeding Associated With Apixaban: A Series of 2 Cases.

OBJECTIVE: To report 2 cases of nonoperable intracranial bleeding associated with apixaban managed by 3-factor prothrombin complex concentrate (PCC3). CASE SUMMARIES: Case 1 presented with a 1.3-cm left parieto-occipital hemorrhage and a thin subdural hematoma (SDH) on the left tentorium of the brain about 6 hours after his last dose of apixaban. Case 2 presented with a 4-mm left parafalcine SDH with time of most recent apixaban dose unknown. The patients received 24.9 to 25.5 U/kg of PCC3 with none to 1 U fresh frozen plasma (FFP) and demonstrated minimal or no progression in lesions measured by repeat computed tomography (CT) after treatment. One patient was discharged to a skilled nursing facility after 8 days; the other patient was discharged to home after 18 days. DISCUSSION: Apixaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and little clinical experience for managing apixaban-associated intracranial bleeding has been reported to date. These cases describe the clinical use of PCC3 to manage parieto-occipital and subdural hemorrhage associated with apixaban in events not requiring surgical intervention. CONCLUSION: In these 2 cases, 25 U/kg PCC3, with none to one unit FFP, ceased apixaban-associated intracranial bleeding without apparent thrombogenic complications.

Profiling lymphocyte interactions at the single-cell level by microfluidic cell pairing.

Establishing a successful immune response requires cell-cell interactions, where the nature of antigen presentation dictates functional outcomes. Methods to study these interactions, however, suffer from limited throughput and a lack of control over cell pairing. Here we describe a microfluidic platform that achieves high-throughput deterministic pairing of lymphocytes with a defined contact time, thereby allowing accurate assessment of early activation events for each pair in controlled microenvironments. More importantly, the platform allows the capture of dynamic processes and static parameters from both partners simultaneously, thus enabling pairwise-correlated multiparametric profiling of lymphocyte interactions over hundreds of pairs in a single experiment. Using our platform, we characterized early activation dynamics of CD8 T cells (OT-1 and TRP1 transnuclear (TN)) and investigated the extent of heterogeneity in T-cell activation and the correlation of multiple readouts. The results establish our platform as a promising tool for quantitative investigation of lymphocyte interactions.

Cell-based biosensor to report DNA damage in micro- and nanosystems.

Understanding how newly engineered micro- and nanoscale materials and systems that interact with cells impact cell physiology is crucial for the development and ultimate adoption of such technologies. Reports regarding the genotoxic impact of forces applied to cells in such systems that can both directly or indirectly damage DNA emphasize the need for developing facile methods to assess how materials and technologies affect cell physiology. To address this need we have developed a TurboRFP-based DNA damage reporter cell line in NIH-3T3 cells that fluoresce to report genotoxic stress caused by a wide variety of agents, from chemical genotoxic agents to UV-C radiation. Our biosensor was successfully implemented in reporting the genotoxic impact of nanomaterials, demonstrating the ability to assess size dependent geno- and cyto-toxicity. The biosensor cells can be assayed in a high throughput, noninvasive manner, with no need for overly sophisticated equipment or additional reagents. We believe that this open-source biosensor is an important resource for the community of micro- and nanomaterials and systems designers and users who wish to evaluate the impact of systems and materials on cell physiology.

Feasibility and effects of TAI CHI for the promotion of sleep quality and quality of life: a single-group study in a sample of older Chinese individuals in Hong Kong.

Poor sleep in later life is a global issue that reduces many individuals' quality of life (QOL). The purpose of this pilot study was to test the feasibility and effects of a simplified tai chi exercise intervention on sleep quality and QOL among Chinese community-dwelling older adults with poor sleep quality. This single-group, descriptive feasibility study included 34 individuals with poor sleep quality who agreed to participate in a 12-week tai chi intervention. Twenty-six individuals completed the program (23.5% dropout rate). Older adults with poor sleep quality who completed the intervention showed significant improvement in the Medical Outcomes Study Short Form-36 mental component and the Pittsburgh Sleep Quality Index global and component scores. The low recruitment and attendance and high dropout rates might be associated with participants' age, gender, and sleep quality. Further long-term studies are required to examine the potential effects of the tai chi intervention. [Journal of Gerontological Nursing, 40(3), 46-52.].

Prevalence and impacts of poor sleep on quality of life and associated factors of good sleepers in a sample of older Chinese adults.

BACKGROUND: Sleep disturbance is a complex health problem in ageing global populations decreasing quality of life among many older people. Geographic, cultural, and ethnic differences in sleep patterns have been documented within and between Western and Asian populations. The aim of this study was to explore sleep problems among Hong Kong seniors by examining the prevalence of poor sleep quality, the relationship between sleep quality and health-related quality of life, and associated factors of good sleepers in different age groups. METHODS: This cross-sectional study used convenience sampling and gathered data during face-to-face interviews. Older community-dwelling individuals (n = 301) were recruited in community centres in 2010. The Pittsburgh Sleep Quality Index and Medical Outcomes Study Short Form-36 were used to measure sleep quality and health-related quality of life. The Medical Outcomes Study Short Form-36 domain scores were compared between good and bad sleepers and between long and short sleepers using Hotelling's T-Square test. SF-36 domain scores were placed into a logistic regression model that controlled for significant demographic variables (gender, educational level, perceived health). RESULTS: Most (77.7%) participants were poor sleepers. Participants who had global Pittsburgh Sleep Quality Index scores <5 and slept ≥5.5 h/night had better health-related quality of life. Vitality, emotional role, physical functioning, and bodily pain domain scores were associated factors of good sleepers in different age groups. CONCLUSIONS: This study found a strong negative association between sleep deprivation (poor quality, short duration) and health-related quality of life. Associated factors for good sleep quality in later life differ among age groups in relation to universal age-related changes, and should be addressed by social policies and health-care programmes.

Controlled self-assembly of monodisperse niosomes by microfluidic hydrodynamic focusing.

Niosomes are synthetic membrane vesicles formed by self-assembly of nonionic surfactant, often in a mixture with cholesterol and dicetyl phosphate. Because of their inner aqueous core and bilayer membrane shell, niosomes are commonly used as carriers of treatment agents for pharmaceutical and cosmetic applications or contrast agents for clinical imaging applications. In those applications, niosomes are considered as a more economical and stable alternative to their biological counterpart (i.e., liposomes). However, conventional bulk method of niosome preparation requires bulk mixing of two liquid phases, which is time-consuming and not well-controlled. Such mixing conditions often lead to large niosomes with high polydispersity in size and thus affect the consistency of niosome dosage or imaging quality. In this study, we present a new method of niosome self-assembly by microfluidic hydrodynamic focusing to improve on the size and size distributions of niosomes. By taking advantage of the rapid and controlled mixing of two miscible fluids (i.e., alcohol and water) in microchannels, we were able to obtain in seconds nanoscaled niosomes with approximately 40% narrower size distributions compared to the bulk method. We further investigated different parameters that might affect on-chip assembly of niosomes, such as (1) conditions for the microfluidic mixing, (2) chemical structures of the surfactant used (i.e., sorbitan esters Span 20, Span 60, and Span 80), and (3) device materials for the microchannel fabrication. This work suggests that microfluidics may facilitate the development and optimization of biomimetic colloidal systems for nanomedicine applications.

Poly(lactide-co-glycolide) nanoparticle assembly for highly efficient delivery of potent therapeutic agents from medical devices.

Controlled delivery of therapeutic agents from medical devices can improve their safety and effectiveness in vivo, by ameliorating the surrounding tissue responses and thus maintaining the functional integrity of the devices. Previously, we presented a new method for providing simultaneous controlled delivery from medical devices, by surface assembly of biodegradable polymer nanoparticles (NPs) encapsulating fluorescent dyes. Here, we continue our investigation with NPs loaded with therapeutic agents, dexamethasone (DEX) or plasmid DNA, and evaluated the bioactivity of the released molecules with macrophage cells associated with inflammation. Over a period of one week, NPs encapsulating DEX released 24.9+/-0.8ng from the probe surface and was successful at suppressing macrophage cell growth by 40+/-10%. This percentage of suppression corresponded to approximately 100% drug delivery efficiency, in comparison with the unencapsulated drug. DNA NP coatings, in contrast, released approximately 1ng of plasmid DNA and were effective at transfecting macrophage cells to express the luciferase gene at 300+/-200 relative luminescence/mg total protein. This amount of luciferase activity corresponded to 100% gene delivery efficiency. Thus, NP coatings were capable of providing continuous release of bioactive agents in sufficient quantities to induce relevant biological effects in cell culture studies. These coatings also remained intact, even after 14 days of incubation with phosphate buffered saline. Although the maximum loading for NP coatings is inherently lower than the more established matrix coating, our study suggests that the NP coatings are a more versatile and efficient approach toward drug delivery or gene delivery from a medical device surface and are perhaps best suited for continuous release of highly potent therapeutic agents.

Simultaneous release of multiple molecules from poly(lactide-co-glycolide) nanoparticles assembled onto medical devices.

Cell and tissue responses to implanted biomaterials often limit their effectiveness and lifetime. This is particularly true for materials implanted into the brain. We present here a new approach for the modification of materials to enable release of multiple agents, which might be useful in modulating tissue responses, without changing the properties of the underlying material, in this case, a silicon probe. Poly(lactide-co-glycolide) nanoparticles (NPs) were assembled onto silicon probe surfaces by electrostatic interactions. Charged NPs were fabricated by altering the properties of the surfactant. NPs formed with poly(ethylene-alt-maleic anhydride) (PEMA) were strongly negatively charged; these NPs assembled onto probes best when suspended at nearly physiological conditions (surface density approximately 83,600+/-3000 particles/mm(2)). The percentage of surface area coverage by the NPs was estimated to be approximately 13% and was maintained over two weeks during constant exposure to PBS. Multiple fluorescent NP populations were attached to the same probe to allow visualization of simultaneous delivery of multiple agents by fluorescence microscopy. Release from NP coatings was reproducible and controllable. The distinct release profiles of each agent from the coatings were preserved upon attachment to the surfaces. The unique feature of this new system is that NPs encapsulating various molecules (i.e. drugs, proteins, or DNA) can be fabricated separately, in advance, and simply mixed prior to attachment. The versatility of this delivery system, therefore, makes it suitable for many applications.

Photopolymerized diffusion-defined polyacrylamide gradient gels for on-chip protein sizing.

We report on a facile diffusion-based photopatterning technique for generating linear and non-linear decreasing pore-size gradients in cross-linked polyacrylamide gels. Diffusion of low viscosity polymer precursor solutions and a two-step photopatterning process were used to define the decreasing pore-size gradient gels in a microfluidic format, thus eliminating the need for controlled mixing and delivery of polymer precursor solutions. We present an analytical model of the non-steady state diffusion process and numerically evaluate that model for direct comparison with empirical characterizations of the gradient gels. We show that the analytical model provides an effective means to predict the steepness and linearity of a desired gradient gel prior to fabrication. To assess electrophoretic assay performance in the microfluidic gradient gels, on-chip sizing of protein samples (20-116 kDa) was investigated. Baseline resolution of six proteins was demonstrated in 4 s using 3.5% to 10% polyacrylamide gradient gels. The demonstrated ability to conduct efficient protein sizing in ultra-short separation lengths (0.3 cm) means low applied electric potentials are needed to achieve the electric field strengths required for protein separations. The low required electric potentials relax operating constraints on electrical components, as is especially important for translation of the assay into pre-clinical and clinical settings. The gradient gel fabrication method reported is amenable to adaptation to non-sizing protein assays, as well as integration with upstream sample preparation steps and subsequent orthogonal downstream assays.

Restoration of lung volume using the Flutter VRP1 or breathing exercise.

A method of chest wall restriction imposed for 30 minutes demonstrated a mean (SD) decrease of 42 (14) per cent in forced vital capacity (FVC) during restrictor application. Following the application of chest wall restriction, 30 healthy subjects then underwent a 15 minute treatment with either Flutter VRP1 (Flutter) or breathing exercise with end-inspiratory hold (BE) after chest wall restriction release. Both Flutter and BE applied for 15 minutes immediately restored FVC to pre-restriction values. Tidal breathing control subjects demonstrated a clinically small but statistically significant decrease in FVC of 3 per cent (p<0.001). Visual analogue assessment of each treatment technique showed BE to be the subject- preferred technique for lung volume restoration. This study shows that in normal subjects, Flutter and BE are equally effective in restoring FVC and superior to tidal breathing.