Economic burden of Huntington disease in Europe and the USA: Results from the Huntington's Disease Burden of Illness study.

BACKGROUND AND PURPOSE: The prevalence of Huntington disease (HD) has increased over time; however, there is a lack of up-to-date evidence documenting the economic burden of HD by disease stage. This study provides an estimate of the annual direct medical, nonmedical, and indirect costs associated with HD from participants in the Huntington's Disease Burden of Illness (HDBOI) study in five European countries and the USA. METHODS: The HDBOI is a retrospective, cross-sectional study. Data collection was conducted between September 2020 and May 2021. Participants were recruited by their HD-treating physicians and categorized as early stage (ES), mid stage (MS), or advanced stage (AS) HD. Data were collected via three questionnaires: a case report form, completed by physicians who collected health care resource use associated with HD to compute direct medical cost, and optional patient and caregiver questionnaires, which included information used to compute nondirect medical and indirect costs. Country-specific unit cost sources were used. RESULTS: HDBOI cost estimates were €12,663 (n = 2094) for direct medical costs, €2984 (n = 359) for nondirect medical costs, and €47,576 (n = 436) for indirect costs. Costs are higher in patients who are at later stages of disease; for example, direct medical costs estimates were €9220 (n = 846), €11,885 (n = 701), and €18,985 (n = 547) for ES, MS, and AS, respectively. Similar trends were observed for nondirect and indirect costs. Costs show large variations between patients and countries. CONCLUSIONS: Cost estimates from the HDBOI study show that people with HD and their caregivers bear a large economic burden that increases as disease progresses.

Bumblebees display characteristics of active vision during robust obstacle avoidance flight.

Insects are remarkable flyers and capable of navigating through highly cluttered environments. We tracked the head and thorax of bumblebees freely flying in a tunnel containing vertically oriented obstacles to uncover the sensorimotor strategies used for obstacle detection and collision avoidance. Bumblebees presented all the characteristics of active vision during flight by stabilizing their head relative to the external environment and maintained close alignment between their gaze and flightpath. Head stabilization increased motion contrast of nearby features against the background to enable obstacle detection. As bees approached obstacles, they appeared to modulate avoidance responses based on the relative retinal expansion velocity (RREV) of obstacles and their maximum evasion acceleration was linearly related to RREVmax. Finally, bees prevented collisions through rapid roll manoeuvres implemented by their thorax. Overall, the combination of visuo-motor strategies of bumblebees highlights elegant solutions developed by insects for visually guided flight through cluttered environments.

Effects of uniform vertical inflow perturbations on the performance of flapping wings.

Flapping wings have attracted significant interest for use in miniature unmanned flying vehicles. Although numerous studies have investigated the performance of flapping wings under quiescent conditions, effects of freestream disturbances on their performance remain under-explored. In this study, we experimentally investigated the effects of uniform vertical inflows on flapping wings using a Reynolds-scaled apparatus operating in water at Reynolds number ≈ 3600. The overall lift and drag produced by a flapping wing were measured by varying the magnitude of inflow perturbation from J Vert = -1 (downward inflow) to J Vert = 1 (upward inflow), where J Vert is the ratio of the inflow velocity to the wing's velocity. The interaction between flapping wing and downward-oriented inflows resulted in a steady linear reduction in mean lift and drag coefficients, C ¯ L and C ¯ D , with increasing inflow magnitude. While a steady linear increase in C ¯ L and C ¯ D was noted for upward-oriented inflows between 0 < J Vert < 0.3 and J Vert > 0.7, a significant unsteady wing-wake interaction occurred when 0.3 ≤ J Vert < 0.7, which caused large variations in instantaneous forces over the wing and led to a reduction in mean performance. These findings highlight asymmetrical effects of vertically oriented perturbations on the performance of flapping wings and pave the way for development of suitable control strategies.

Performance of passively pitching flapping wings in the presence of vertical inflows.

The successful implementation of passively pitching flapping wings strongly depends on their ability to operate efficiently in wind disturbances. In this study, we experimentally investigated the interaction between a uniform vertical inflow perturbation and a passive-pitching flapping wing using a Reynolds-scaled apparatus operating in water at Reynolds number ≈3600. A parametric study was performed by systematically varying the Cauchy number (Ch) of the wings from 0.09 to 11.52. The overall lift and drag, and pitch angle of the wing were measured by varying the magnitude of perturbation fromJVert= -0.6 (downward inflow) toJVert= 0.6 (upward inflow) at eachCh, whereJVertis the ratio of the inflow velocity to the wing's velocity. We found that the lift and drag had remarkably different characteristics in response to bothChandJVert. Across allCh, while mean lift tended to increase as the inflow perturbation varied from -0.6 to 0.6, drag was significantly less sensitive to the perturbation. However effect of the vertical inflow on drag was dependent onCh, where it tended to vary from an increasing to a decreasing trend asChwas changed from 0.09 to 11.52. The differences in the lift and drag with perturbation magnitude could be attributed to the reorientation of the net force over the wing as a result of the interaction with the perturbation. These results highlight the complex interactions between passively pitching flapping wings and freestream perturbations and will guide the design of miniature flying crafts with such architectures.

Gap perception in bumblebees.

A number of insects fly over long distances below the natural canopy, where the physical environment is highly cluttered consisting of obstacles of varying shape, size and texture. While navigating within such environments, animals need to perceive and disambiguate environmental features that might obstruct their flight. The most elemental aspect of aerial navigation through such environments is gap identification and 'passability' evaluation. We used bumblebees to seek insights into the mechanisms used for gap identification when confronted with an obstacle in their flight path and behavioral compensations employed to assess gap properties. Initially, bumblebee foragers were trained to fly though an unobstructed flight tunnel that led to a foraging chamber. After the bees were familiar with this situation, we placed a wall containing a gap that unexpectedly obstructed the flight path on a return trip to the hive. The flight trajectories of the bees as they approached the obstacle wall and traversed the gap were analyzed in order to evaluate their behavior as a function of the distance between the gap and a background wall that was placed behind the gap. Bumblebees initially decelerated when confronted with an unexpected obstacle. Deceleration was first noticed when the obstacle subtended around 35 deg on the retina but also depended on the properties of the gap. Subsequently, the bees gradually traded off their longitudinal velocity to lateral velocity and approached the gap with increasing lateral displacement and lateral velocity. Bumblebees shaped their flight trajectory depending on the salience of the gap, indicated in our case by the optic flow contrast between the region within the gap and on the obstacle, which decreased with decreasing distance between the gap and the background wall. As the optic flow contrast decreased, the bees spent an increasing amount of time moving laterally across the obstacles. During these repeated lateral maneuvers, the bees are probably assessing gap geometry and passability.

Bees with attitude: the effects of directed gusts on flight trajectories.

Flight is a complicated task at the centimetre scale particularly due to unsteady air fluctuations which are ubiquitous in outdoor flight environments. Flying organisms deal with these difficulties using active and passive control mechanisms to steer their body motion. Body attitudes of flapping organisms are linked with their resultant flight trajectories and performance, yet little is understood about how isolated unsteady aerodynamic phenomena affect the interlaced dynamics of such systems. In this study, we examined freely flying bumblebees subject to a single isolated gust to emulate aerodynamic disturbances encountered in nature. Bumblebees are expert commanders of the aerial domain as they persistently forage within complex terrain elements. By tracking the three-dimensional dynamics of bees flying through gusts, we determined the sequences of motion that permit flight in three disturbance conditions: sideward, upward and downward gusts. Bees executed a series of passive impulsive maneuvers followed by active recovery maneuvers. Impulsive motion was unique in each gust direction, maintaining control by passive manipulation of the body. Bees pitched up and slowed down at the beginning of recovery in every disturbance, followed by corrective maneuvers which brought body attitudes back to their original state. Bees were displaced the most by the sideward gust, displaying large lateral translations and roll deviations. Upward gusts were easier for bees to fly through, causing only minor flight changes and minimal recovery times. Downward gusts severely impaired the control response of bees, inflicting strong adverse forces which sharply upset trajectories. Bees used a variety of control strategies when flying in each disturbance, offering new insights into insect-scale flapping flight and bio-inspired robotic systems.This article has an associated First Person interview with the first author of the paper.

The gust-mitigating potential of flapping wings.

Nature's flapping-wing flyers are adept at negotiating highly turbulent flows across a wide range of scales. This is in part due to their ability to quickly detect and counterract disturbances to their flight path, but may also be assisted by an inherent aerodynamic property of flapping wings. In this study, we subject a mechanical flapping wing to replicated atmospheric turbulence across a range of flapping frequencies and turbulence intensities. By means of flow visualization and surface pressure measurements, we determine the salient effects of large-scale freestream turbulence on the flow field, and on the phase-average and fluctuating components of pressure and lift. It is shown that at lower flapping frequencies, turbulence dominates the instantaneous flow field, and the random fluctuating component of lift contributes significantly to the total lift. At higher flapping frequencies, kinematic forcing begins to dominate and the flow field becomes more consistent from cycle to cycle. Turbulence still modulates the flapping-induced flow field, as evidenced in particular by a variation in the timing and extent of leading edge vortex formation during the early downstroke. The random fluctuating component of lift contributes less to the total lift at these frequencies, providing evidence that flapping wings do indeed provide some inherent gust mitigation.

Emulating avian orographic soaring with a small autonomous glider.

This paper explores a method by which an unpowered, fixed-wing micro air vehicle (MAV) may autonomously gain height by utilising orographic updrafts in urban environments. These updrafts are created when wind impinges on both man-made and natural obstacles, and are often highly turbulent and very localised. Thus in contrast to most previous autonomous soaring research, which have focused on large thermals and ridges, we use a technique inspired by kestrels known as 'wind-hovering', in order to maintain unpowered flight within small updrafts. A six-degree-of-freedom model of a MAV was developed based on wind-tunnel tests and vortex-lattice calculations, and the model was used to develop and test a simple cascaded control system designed to hold the aircraft on a predefined trajectory within an updraft. The wind fields around two typical updraft locations (a building and a hill) were analysed, and a simplified trajectory calculation method was developed by which trajectories for height gain can be calculated on-board the aircraft based on a priori knowledge of the wind field. The results of simulations are presented, demonstrating the behaviour of the system in both smooth and turbulent flows. Finally, the results from a series of flight tests are presented. Flight tests at the hill were consistently successful, while flights around the building could not be sustained for periods of more than approximately 20 s. The difficulty of operating near a building is attributable to significant levels of low-frequency unsteadiness (gustiness) in the oncoming wind during the flight tests, effectively resulting in a loss of updraft for sustained periods.

Rolling with the flow: bumblebees flying in unsteady wakes.

Our understanding of how variable wind in natural environments affects flying insects is limited because most studies of insect flight are conducted in either smooth flow or still air conditions. Here, we investigate the effects of structured, unsteady flow (the von Karman vortex street behind a cylinder) on the flight performance of bumblebees (Bombus impatiens). Bumblebees are 'all-weather' foragers and thus frequently experience variable aerial conditions, ranging from fully mixed, turbulent flow to unsteady, structured vortices near objects such as branches and stems. We examined how bumblebee flight performance differs in unsteady versus smooth flow, as well as how the orientation of unsteady flow structures affects their flight performance, by filming bumblebees flying in a wind tunnel under various flow conditions. The three-dimensional flight trajectories and orientations of bumblebees were quantified in each of three flow conditions: (1) smooth flow, (2) the unsteady wake of a vertical cylinder (inducing strong lateral disturbances) and (3) the unsteady wake of a horizontal cylinder (inducing strong vertical disturbances). In both unsteady conditions, bumblebees attenuated the disturbances induced by the wind quite effectively, but still experienced significant translational and rotational fluctuations as compared with flight in smooth flow. Bees appeared to be most sensitive to disturbance along the lateral axis, displaying large lateral accelerations, translations and rolling motions in response to both unsteady flow conditions, regardless of orientation. Bees also displayed the greatest agility around the roll axis, initiating voluntary casting maneuvers and correcting for lateral disturbances mainly through roll in all flow conditions. Both unsteady flow conditions reduced the upstream flight speed of bees, suggesting an increased cost of flight in unsteady flow, with potential implications for foraging patterns and colony energetics in natural, variable wind environments.

Chromatin remodelling in plant light signalling.

The structure and compaction of chromatin exerts a major regulatory influence on eukaryotic transcription. Changes in both histone composition and post-translational modifications of individual histone proteins can lead to remodelling of higher order chromatin structure. Chromatin remodelling regulates transcriptional activity through modifying gene accessibility, via DNA/histone interactions and the recruitment of non-histone proteins to DNA. Plant growth and development is regulated by the integration of multiple environmental signals. Of these, light is one of the most important. Chromatin remodelling processes have been identified in plants following a variety of different light treatments. These include the initiation of seedling de-etiolation, changes in photon irradiance and ultraviolet-B radiation exposure. In this review, we will summarize the roles of chromatin remodelling in plant photomorphogenesis and discuss these in the wider context of plant environmental adaptation.

Bisphosphonate use and hip fracture epidemiology: ecologic proof from the contrary.

AIM: The objective of this article is to evaluate the relationship between the changes in prescriptions of antiosteoporotic drugs (mainly the rapid fall in the use of bisphosphonates [BPs]) and standardized hip fracture (HF) rates over the period 2005-2008 in the Australian Capital Territory (ACT). METHODS: Annual sex- and age-specific HF rates (per 100,000 population) were determined and standardized using the Australian 2006 population census. Data on the annual prescriptions of BPs (mainly alendronate and risedronate), strontium ranelate, and hormone replacement therapy were obtained from the Australian Pharmaceutical Benefits Scheme (PBS) and Repatriation Australian Pharmaceutical Benefits Scheme (RPBS) databases. RESULTS: In the ACT, the peak annual number of prescriptions for BPs was observed in 2006. Following reports linking osteonecrosis of the jaw with BP use, the number of BP prescriptions dropped by 14% in 2007-2008 compared with 2005, when the lowest HF rates were recorded. The reduction in BP prescriptions coincided with increased HF rates in females in 2007 (+22.6%) and in 2008 (+25.2%) compared with 2005; in males, HF incidence declined by 6.6% and 16.7%, respectively. The proportion of filled prescriptions for strontium ranelate, risedronate, and alendronate in 2007-2008 was 1:8.4:15.5, indicating that BPs were the dominant antiosteoporotic drugs. There was an inverse statistically significant relationship between the total annual number of BP prescriptions and standardized HF incidence rates for the 10-year period 1999-2008. CONCLUSION: Although currently there is no clear understanding of factors contributing to changing HF epidemiology, the available evidence suggests that much of the decline in HF rates is due to the use of BPs. The fall in the use of BPs is associated with an increase in HF rates in females, indicating that BPs should still be considered the first-line medications for the prevention and treatment of osteoporosis. Our results need to be confirmed in other populations and countries.

Using a monitored test to assess risk of aspiration in postoperative patients.

Pulmonary aspiration is associated with high morbidity and mortality rates. Older adult patients have been shown to be particularly at risk for aspiration. A randomized controlled trial was conducted to investigate the efficacy of a simple, noninvasive screening test-the monitored sip test-in identifying patients at risk for aspiration, including "silent aspirators." Based on clinical judgment using the study's outcome measures, incidence of aspiration-related lung injury was high (ie, 37.5%); however, no identification of patients at risk for aspiration occurred after either the use of the monitored sip test or routine cautious introduction of fluids during the data collection phase of the study.

Increased mammographic screening and use of percutaneous image-guided core biopsy in non-palpable breast cancer: impact on surgical treatment.

BACKGROUND: Major efforts are being directed at the early diagnosis of breast cancer. The diagnosis rate of non-palpable tumors is steadily growing as a result of increased screening by mammography. In most patients with non-palpable lesions, percutaneous image-guided biopsies have replaced wire localization with surgical excision for obtaining tissue diagnosis. In recent years the Israel Ministry of Health initiated a mammograpy screening program. Percutaneous image-guided biopsies have also become widely available. OBJECTIVE: To assess the impact of these changes on breast cancer surgical treatment in our hospital. METHODS: The charts of 483 patients operated on in our department for primary breast carcinoma during the years 1997 to mid-2001 were reviewed. Data on the mode of diagnosis, tumor stage, resection margins, and number and types of operations were recorded and analyzed. The term non-palpable tumors relates to tumors necessitating wire localization for surgical excision. RESULTS: The percentage of patients diagnosed with non-palpable tumors rose from 16.2% in 1997 to 47.4% in 2001, with an average size of 2.6 cm for palpable and 1.7 cm for non-palpable tumors. The rate of preoperative diagnosis for non-palpable tumors rose from 6.2% in 1997 to 96.4% in 2001. The rate of involved or very close margins was reduced by 73% in the patient group diagnosed preoperatively as compared to those without a preoperative diagnosis (10.6% vs. 39.4%). Finally, the percentage of patients who had two operations fell from 56.2% in 1997 to 11.1% in 2001. CONCLUSIONS: The mammography screening program in Jerusalem in 1997-2001 was effective in increasing the relative percentage of non-palpable breast cancers with reduced tumor size at diagnosis. The improved availability of preoperative tissue diagnosis in these patients reduced the number of surgical procedures needed.

Postprandial systolic blood pressure responses of older people in residential care: association with risk of falling.

BACKGROUND: The association between postprandial blood pressure, falls and medications is controversial. OBJECTIVE: To investigate cardiovascular responses to meals in elderly people together with clinical associations and therapeutic issues. METHODS: A cross-sectional observational study of 179 semi-independent older people (age 83.2 +/- 7.0 years) in residential care facilities was undertaken. Data on the frequency of falls, medical and medication history and measurement of blood pressure before and after a breakfast meal, and then after standing and walking after the meal were documented. RESULTS: Postprandial hypotension (>/=20 mm Hg fall in systolic blood pressure (SBP)) and low absolute SBP (

A multicenter, case-control study of the effects of antihypertensive therapy on orthostatic hypotension, postprandial hypotension, and falls in octo- and nonagenarians in residential care facilities.

BACKGROUND: Orthostatic hypotension, postprandial hypotension, and falls are considered to be adverse drug reactions of antihypertensive therapy in older people with comorbidities. Concerns regarding these adverse events may limit the use of antihypertensive agents in this group of people. OBJECTIVE: The aim of this study was to determine the relationship between antihypertensive therapy in octo- and nonagenarians and the risk for orthostatic hypotension, postprandial hypotension, and falls. METHODS: This was a case-control study of octo- and nonagenarians living in residential care facilities who were receiving antihypertensive therapy and a control group who were not receiving antihypertensive therapy. RESULTS: A total of 119 patients, 77 who were receiving regular antihypertensive therapy and 42 who were not taking any antihypertensive agents, were enrolled in the study. The prevalence of antihypertensive use, orthostatic hypotension, postprandial hypotension, and falls was high (65%, 29%, 57%, and 45%, respectively). There were no associations between antihypertensive therapy and orthostatic hypotension, postprandial hypotension, and falls. When individual classes of antihypertensive agents were examined, the only observed association was a negative association (ie, a protective effect) between potassium-sparing diuretics and falls (odds ratio, 0.2; 95% CI, 0.04-1.0). CONCLUSION: Antihypertensive therapy was not associated with an increased risk for orthostatic hypotension, postprandial hypotension, or falls in this case-control study of octo- and nonagenarians living in residential care facilities.