Mammalian reverse genetics without crossing reveals Nr3a as a short-sleeper gene

The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%–100%). In addition, we developed a respiration-based fully automated noninvasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Chinese cultural competency and Australian law students: Reflections on the design of short term mobility programs

There is an emerging need for Australia’s law graduates to better understand the unique challenges and opportunities in our largest trading partner, China. Similarly, as China opens up to the world, its graduates are increasingly well-poised to make an indelible mark on Chinese-Australian relations, particularly in the areas of finance, property, trade and commerce. Chinese and Australian law schools must urgently develop a deeper awareness of each other’s language, culture and political systems in their graduates. The purpose of this article is to highlight the importance of Chinese cultural competency to Australian legal education and reflect on projects that enable students to attain a level of cultural competency over a short period. We do this by considering a recent ‘short term mobility project’ in Wuhan, China.

The lived experience of diagnosis delivery in motor neurone disease: A sociological-phenomenological study

Relatively few previous studies of individuals receiving a diagnosis of Motor Neurone Disease within the UK health care system have employed qualitative approaches to examine the diagnostic journey from a patient perspective. A qualitative sociological study was undertaken, involving interviews with 42 participants diagnosed with MND, to provide insight into their experiences of undergoing testing and receiving a diagnosis. Adopting a sociological-phenomenological perspective, this article examines key themes that emerged from participant accounts surrounding the lived experience of the diagnostic journey. The key themes that emerged were: The diagnostic quest; living with uncertainty; hearing bad news; communication difficulties; and a reified body of medical interest. In general, doctor-patient communication both at pre and post diagnosis was experienced as highly stressful, distressing and profoundly upsetting. Participants reported such distress as being due to the mode of delivery and communication strategies used by health professionals. We therefore suggest that professional training needs to emphasize the importance to health professionals of fostering greater levels of tact, sensitivity and empathy towards patients diagnosed with devastating, life-limiting illnesses such as MND.

Morphological changes in the conjunctiva, episclera and sclera following short-term miniscleral contact lens wear in rigid lens neophytes

PURPOSE To quantify the influence of short-term wear of miniscleral contact lenses on the morphology of the corneo-scleral limbus, the conjunctiva, episclera and sclera. METHODS OCT images of the anterior eye were captured before, immediately following 3h of wear and then 3h after removal of a miniscleral contact lens for 10 young (27±5 years) healthy participants (neophyte rigid lens wearers). The region of analysis encompassed 1mm anterior, to 3.5mm posterior to the scleral spur. Natural diurnal variations in thickness were measured on a separate day and compensated for in subsequent analyses. RESULTS Following 3h of lens wear, statistically significant tissue thinning was observed across all quadrants, with a mean decrease in thickness of -24.1±3.6μm (p<0.001), which diminished, but did not return to baseline 3h after lens removal (-16.9±1.9μm, p<0.001). The largest tissue compression was observed in the superior quadrant (-49.9±8.5μm, p<0.01) and in the annular zone 1.5mm from the scleral spur (-48.2±5.7μm), corresponding to the approximate edge of the lens landing zone. Compression of the conjunctiva/episclera accounted for about 70% of the changes. CONCLUSIONS Optimal fitting miniscleral contact lenses worn for three hours resulted in significant tissue compression in young healthy eyes, with the greatest thinning observed superiorly, potentially due to the additional force of the eyelid, with a partial recovery of compression 3h after lens removal. Most of the morphological changes occur in the conjunctiva/episclera layers.

Carbon dioxide emissions in the short run: The rate and sources of economic growth matter

This paper investigates the short-run effects of economic growth on carbon dioxide emissions from the combustion of fossil fuels and the manufacture of cement for 189 countries over the period 1961-2010. Contrary to what has previously been reported, we conclude that there is no strong evidence that the emissions-income elasticity is larger during individual years of economic expansion as compared to recession. Significant evidence of asymmetry emerges when effects over longer periods are considered. We find that economic growth tends to increase emissions not only in the same year, but also in subsequent years. Delayed effects - especially noticeable in the road transport sector - mean that emissions tend to grow more quickly after booms and more slowly after recessions. Emissions are more sensitive to fluctuations in industrial value added than agricultural value added, with services being an intermediate case. On the expenditure side, growth in consumption and growth in investment have similar implications for national emissions. External shocks have a relatively large emissions impact, and the short-run emissions-income elasticity does not appear to decline as incomes increase. Economic growth and emissions have been more tightly linked in fossil-fuel rich countries.

Development and reproducibility of a short questionnaire to measure use and usability of custom-made orthopaedic shoes

OBJECTIVE To develop a short and easy to use questionnaire to measure use and usability of custom-made orthopaedic shoes, and to investigate its reproducibility. DESIGN Development of the questionnaire (Monitor Orthopaedic Shoes) was based on a literature search, expert interviews, 2 expert meetings, and exploration and testing of reproducibility. The questionnaire comprises 2 parts: a pre part, measuring expectations; and a post part, measuring experiences. Patients The pre part of the final version was completed twice by 37 first-time users before delivery of their orthopaedic shoes. The post part of the final version was completed twice by 39 first-time users who had worn their orthopaedic shoes for 2–4 months. RESULTS High reproducibility scores (Cohen’s kappa > 0.60 or intra class correlation > 0.70) were found in all but one question of both parts of the final version of the Monitor Orthopaedic Shoes questionnaire. The smallest real difference on a visual analogue scale (100 mm) ranged from 21 to 50 mm. It took patients approximately 15 minutes to complete one part. CONCLUSION Monitor Orthopaedic Shoes is a practical and reproducible questionnaire that can measure relevant aspects of use and usability of orthopaedic shoes from a patient’s perspective.

Short and long term mortality rates after a lower limb amputation

Objective To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75–84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.

Tissue compression following short-term miniscleral contact lens wear

To quantify regional (nasal, superior, temporal and inferior) and location specific (corneal and scleral) tissue compression following short-term miniscleral contact lens wear.

Significance of a short-term test drive for prospective plug-in electric vehicle consumers: An exploratory study

The test drive is a well-known step in car buying. In the emerging plug-in electric vehicle (PEV) market, however, the influence of a pre-purchase test drive on a consumer's inclination to purchase is unknown. Policy makers and industry participants both are eager to understand what factors motivate vehicle consumers at the point-of-sale. A number of researchers have used choice models to shed light on consumer perceptions of PEVs, and others have investigated consumer change in disposition toward a PEV over the course of a trial, wherein test driving a PEV may take place over a number of consecutive days, weeks or months. However, there is little written on the impact of a short-term test drive - a typical experience at dealerships or public "ride-and-drive" events. The impact of a typical test drive, often measured in minutes of driving, is not well understood. This paper first presents a synthesis of the literature on the effect of PEV test drives as they relate to consumer disposition toward PEVs. An analysis of data obtained from an Australian case study whereby attitudinal and stated preference data were collected pre- and post- test drive at public "ride-and-drive" event held Brisbane, Queensland in March 2014 using a custom-designed iPad application. Motorists' perceptions and choice preferences around PEVs were captured, revealing the relative importance of their experience behind the wheel. Using the Australian context as a case-study, this paper presents an exploratory study of consumers' stated preferences toward PEVs both before and after a short test drive.

Middle-aged and elderly Finnish households considering moving, their preferences, and potential downsizing amidst changing life course and housing careers

We examine the moving and housing preferences of middle-aged and older in Finland, a country where population composition and movement through the life course are changing. A logistic regression reveals that middle-aged, moderate income residents, renters, those who have lived in their houses only a short time, and residents who are generally dissatisfied are most likely to consider moving. Downsizing appeals to residents with lower incomes who live alone, and who have been in their current houses longer. All potential movers agree on the importance of transportation access and a neighborhood grocery store; however, those preferring to downsize are also interested in house and neighborhood design as well as services that will allow aging in place. Income limitations may create affordability problems for some potential movers.

Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a valid screening tool in chemotherapy outpatients

Purpose In the oncology population where malnutrition prevalence is high, more descriptive screening tools can provide further information to assist triaging and capture acute change. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a component of a nutritional assessment tool which could be used for descriptive nutrition screening. The purpose of this study was to conduct a secondary analysis of nutrition screening and assessment data to identify the most relevant information contributing to the PG-SGA SF to identify malnutrition risk with high sensitivity and specificity. Methods This was an observational, cross-sectional study of 300 consecutive adult patients receiving ambulatory anti-cancer treatment at an Australian tertiary hospital. Anthropometric and patient descriptive data were collected. The scored PG-SGA generated a score for nutritional risk (PG-SGA SF) and a global rating for nutrition status. Receiver operating characteristic curves (ROC) were generated to determine optimal cut-off scores for combinations of the PG-SGA SF boxes with the greatest sensitivity and specificity for predicting malnutrition according to scored PG-SGA global rating. Results The additive scores of boxes 1–3 had the highest sensitivity (90.2 %) while maintaining satisfactory specificity (67.5 %) and demonstrating high diagnostic value (AUC = 0.85, 95 % CI = 0.81–0.89). The inclusion of box 4 (PG-SGA SF) did not add further value as a screening tool (AUC = 0.85, 95 % CI = 0.80–0.89; sensitivity 80.4 %; specificity 72.3 %). Conclusions The validity of the PG-SGA SF in chemotherapy outpatients was confirmed. The present study however demonstrated that the functional capacity question (box 4) does not improve the overall discriminatory value of the PG-SGA SF.

Reflections from East Asia's ageing population: An interaction designers' challenge

As Asia experiences the demographic imbalance between working and ageing populations, the need for attention in this area is highlighted. The shift of a country's age structure that results from people having small families and living long lives, where previously they had large families and lived short lives, results in more workers and fewer dependents creating economic growth, known as the demographic dividend. However for a generation after this bulge and dividend, a disproportionate number of older people must be supported by a smaller working population, a current concern in Asia with its rapidly growing number of older adults. This extended abstract draws practical and unique insights from three of the oldest and richest nations in Asia - Japan, South Korea and China, on the perspective of interactive technology design for older adults. ICT has powerful potential to ameliorate the imbalance in the population demographic through its potential to leverage various kinds of support. As HCI researchers, this is a challenge we embrace; a challenge for the ageing society of unique individuals to exploit the technologies that they have helped to create. The paper draws lessons from key sample studies, one from each country, which aimed to understand their ageing population. The insights for interaction designers are presented in the form of a practical set of reflections to guide the authors, who are in the early stages of research on technology design for older adults.