The goal of this study was to compare the ability of morphology and molecular-based surveys to estimate species richness for two species-rich diatom genera, Chaetoceros Ehrenb. and Thalassiosira Cleve, in the Bay of Fundy. Phytoplankton tows were collected from two sites at intervals over two years and subsampled for morphology-based surveys (2010, 2011), a culture-based DNA reference library (DRL; 2010), and a molecular-based survey (2011). The DRL and molecular-based survey utilized the 3′ end of the RUBISCO large subunit (rbcL-3P) to identify genetic species groups (based on 0.1% divergence in rbcL-3P), which were subsequently identified morphologically to allow comparisons to the morphology-based survey. Comparisons were compiled for the year (2011) by site (n = 2) and by season (n = 3). Of the 34 taxa included in the comparisons, 50% of taxa were common to both methods, 35% were unique to the molecular-based survey, and 12% were unique to the morphology-based survey, while the remaining 3% of taxa were unidentified genetic species groups. The morphology-based survey excelled at identifying rare taxa in individual tow subsamples, which were occasionally missed with the molecular approach used here, while the molecular methods (the DRL and molecular-based survey), uncovered nine cryptic species pairs and four previously overlooked species. The last mentioned were typically difficult to identify and were generically assigned to Thalassiosira spp. during the morphology-based survey. Therefore, for now we suggest a combined approach encompassing routine morphology-based surveys accompanied by periodic molecular-based surveys to monitor for cryptic and difficult to identify taxa. As sequencing technologies improve, molecular-based surveys should become routine, leading to a more accurate representation of species composition and richness in monitoring programs.
The gene product of M. tuberculosis Rv2969c is shown to be a disulfide oxidase enzyme that has a canonical DsbA-like fold with novel structural and functional characteristics.
The bacterial disulfide machinery is an attractive molecular target for developing new antibacterials because it is required for the production of multiple virulence factors. The archetypal disulfide oxidase proteins in Escherichia coli (Ec) are DsbA and DsbB, which together form a functional unit: DsbA introduces disulfides into folding proteins and DsbB reoxidizes DsbA to maintain it in the active form. In Mycobacterium tuberculosis (Mtb), no DsbB homologue is encoded but a functionally similar but structurally divergent protein, MtbVKOR, has been identified. Here, the Mtb protein Rv2969c is investigated and it is shown that it is the DsbA-like partner protein of MtbVKOR. It is found that it has the characteristic redox features of a DsbA-like protein: a highly acidic catalytic cysteine, a highly oxidizing potential and a destabilizing active-site disulfide bond. Rv2969c also has peptide-oxidizing activity and recognizes peptide segments derived from the periplasmic loops of MtbVKOR. Unlike the archetypal EcDsbA enzyme, Rv2969c has little or no activity in disulfide-reducing and disulfide-isomerase assays. The crystal structure of Rv2969c reveals a canonical DsbA fold comprising a thioredoxin domain with an embedded helical domain. However, Rv2969c diverges considerably from other DsbAs, including having an additional C-terminal helix (H8) that may restrain the mobility of the catalytic helix H1. The enzyme is also characterized by a very shallow hydrophobic binding surface and a negative electrostatic surface potential surrounding the catalytic cysteine. The structure of Rv2969c was also used to model the structure of a paralogous DsbA-like domain of the Ser/Thr protein kinase PknE. Together, these results show that Rv2969c is a DsbA-like protein with unique properties and a limited substrate-binding specificity.
DsbA; VKOR; DsbB; antibacterial target; oxidative folding; virulence; thioredoxin
Insomnia is a common problem among older adults. In particular, older adults experience insomnia coupled with early morning awakenings due to an interaction between age-related changes in circadian rhythm timing coupled with behavior changes that contribute to sustained poor sleep. Cognitive–behavioral therapy for insomnia (CBT-I), at times coupled with circadian interventions (e.g., timed light exposure), are likely to be most successful in optimizing sleep quality. In delivering CBT-I to older adults, modifications are sometimes necessary to accommodate for medical problems, lifestyle, social factors, and patient preferences. Addition of circadian interventions can ameliorate the negative effects of inappropriately timed sleep as well. These treatment methods can be highly effective and benefits can be long-standing. A case example is used to illustrate these points.
insomnia; circadian rhythms; advanced sleep phase syndrome; aging; cognitive–behavioral therapy; light therapy
To describe sleep patterns in older adults living in assisted living facilities (ALFs) and to explore the relationship between sleep disturbance and quality of life, functional status, and depression over 6 months of follow-up.
Prospective, observational cohort study. SETTING: Eighteen ALFs in the Los Angeles area. PARTICIPANTS: One hundred twenty-one ALF residents aged 65 and older (mean age 85.3, 86% female, 88% non-Hispanic white).
Data were collected at baseline and 3 and 6 months after enrollment. Data collected were demographics, physical and cognitive functioning, depression, quality of life, comorbidities, medications, and subjective (i.e., questionnaires) and objective (i.e., 3 days and nights of wrist actigraphy) measures of sleep.
Sixty-five percent of participants reported clinically significant sleep disturbance on the Pittsburgh Sleep Quality Index, and objective wrist actigraphy confirmed poor sleep quality. In regression analyses including sleep variables and other predictors, more self-reported sleep disturbance at baseline was associated with worse health-related quality of life (Medical Outcomes Study 12-item Short Form Survey Mental Component Summary score) and worse depressive symptoms five-item Geriatric Depression Scale at follow-up. Worse nighttime sleep (according to actigraphy) at baseline was associated with worse activities of daily living functioning and more depressive symptoms at follow-up.
Sleep disturbance is common in older ALF residents, and poor sleep is associated with declining functional status and quality of life and greater depression over 6 months of follow-up. Studies are needed to determine whether improving sleep in ALF residents will result in improvements in these outcomes. Well-established treatments should be adapted for use in ALFs and systematically evaluated in future research.
sleep; assisted living facilities; depression; quality of life; functional status
Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation.
Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge − admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 AM, 2 PM, 4:30 PM, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures.
The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 PM, 4:30 PM, and bedtime. A morning cortisol rise was also associated with greater mFIM change.
Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are “at risk” of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay.
Cortisol; Older adults; Rehabilitation; Inpatient; Functional Status
To evaluate whether objectively- and subjectively-measured sleep disturbances persist among older adults in assisted living facilities (ALFs) and to identify predictors of sleep disturbance in this setting.
Prospective, observational cohort study
Setting and Participants
121 residents, aged ≥ 65 years, in 18 ALFs in the Los Angeles area
Objective (actigraphy) and subjective (Pittsburgh Sleep Quality Index, PSQI) sleep measures were collected at baseline and 3- and 6-month follow-up. Predictors of baseline sleep disturbance tested in bivariate analyses and multiple regression models included demographics, Mini-Mental State Examination score, number of comorbidities, nighttime sedating medication use, functional status (Activities of Daily Living, ADL; Instrumental Activities of Daily Living, IADL), restless legs syndrome, and sleep apnea risk.
Objective and subjective sleep measures were similar at baseline, 3- and 6-month follow-up (objective nighttime total sleep (hours) 6.3, 6.5, and 6.4; objective nighttime percent sleep 77.2, 77.7, and 78.3; and PSQI total score 8.0, 7.8, and 7.7, respectively). The mean baseline nighttime percent sleep decreased by 2% for each additional unit increase in baseline comorbid conditions (measured as number of conditions) and increased by 4.5% for each additional unit increase in baseline ADLs (measured as number of ADLs), in a multiple regression model.
In this study, we found that objectively- and subjectively-measured sleep disturbances are persistent among ALF residents and are related to greater number of comorbidities and poorer functional status at baseline. Interventions are needed to improve sleep in this setting.
sleep; assisted living facilities; long-term care
To explore the unique impact of poor sleep and symptoms of depression on sleep quality for up to one year after inpatient post-acute rehabilitation among older adults.
Prospective longitudinal cohort study.
Two in-patient post-acute rehabilitation facilities
245 individuals over age 65 years (mean age=80 years, 38% female)
Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) during the post-acute care stay twice to evaluate pre-illness sleep quality and sleep quality during the post-acute care stay, and again at 3, 6, 9 and 12-months follow-up. Demographics, symptoms of depression, cognitive functioning, and comorbidities were also assessed.
Across time points, sleep was significantly disturbed for many individuals. Nested regression models predicting PSQI total score at 3, 6, 9 and 12 months showed that variables entered in Block 1 (age, gender, cognitive functioning and comorbidities) were significant predictors of poor sleep at 6-months, but not at 3, 9 or 12 months follow-up. Depression (Block 2) and pre-illness PSQI total score (Block 3) were significant predictors of PSQI total score at all follow-up time points. PSQI total score during post-acute care (Block 4) explained a significant proportion of variance only at the 3-month follow-up.
This study confirms that chronic poor sleep is common among older adults during post-acute rehabilitation, and resolution of sleep disturbance after acute health events may be a lengthy process. Our findings expand understanding of the role of depressive symptoms and pre-existing sleep complaints in predicting poor sleep over time among these vulnerable older adults.
rehabilitation; sleep; aging; depression
Sleep problems among assisted living facility (ALF) residents are not well understood, and sleep-related differences between ALF residents and home-dwelling older adults have not been examined.
We compared sleep patterns in 19 ALF residents to sleep patterns in 19 matched home-dwelling older people (age ≥65 years). All were participating in the follow-up portion of a longitudinal study of sleep and functional outcomes following post-acute rehabilitation. Sleep was assessed with the Pittsburgh Sleep Quality Index and 1 week of wrist actigraphy.
By actigraphy, ALF residents awoke earlier in the morning and exhibited more nighttime awakenings compared to home-dwelling participants (06:50 hours ± 1:29 hours vs 07:51 hours ± 1:19 hours and 19.5 ± 8.5 vs 12.9 ± 11.4 awakenings, respectively).
Larger studies are needed to confirm these initial findings that ALF residents have more disrupted sleep than do home-dwelling older persons, and to examine the functional and health consequences of poor sleep among ALF residents.
Sleep; Aging; Circadian rhythms; Assisted living
The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital.
AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital.
Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution.
AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department.
User needs elicitation; Analytic hierarchy process; AHP; Medical decision-making; Medical device
In pulmonary rehabilitation (PR) effective measures have been taken while in analyzing a patient’s intervention with the help of entry to exit evaluations. The absence of an objective and quantifiable scale are limitations of PR that allow analyzing of a patient’s self reported symptoms throughout PR. The Breathlessness, Cough and Sputum Scale (BCSS©) is used to predict patient exacerbations by evaluating common symptoms identified in the COPD population. This study used the BCSS© survey to track complex symptom changes throughout the course of PR intervention. The BCSS© tool measured the patient’s self reported symptoms in real time for each visit when patient enrolled in PR.
Thirty-five patients with COPD from three outpatient PR centers were asked to report the severity of breathlessness, cough, and sputum prior to each PR session using the BCSS© survey.
There was a significant decrease in self reported symptoms of the mean BCSS© score from entry 4.6(± 2.9) to exit 2.3 (± 2.5), p < 0.001. The results showed variable decrease in the self reported symptoms with more PR visits. The secondary outcome showed high correlations with quality of life measures using the Pulmonary Function Status Scale (PFSS) on entry and exit to PR.
The BCSS© tool is an effective means for measuring the impact of PR on improving patient tolerance and self-reported symptoms as a result of COPD. More research is needed to better assess the complex symptoms of COPD patients in PR to enhance programmatic outcomes.
Rehabilitation; quality of life; dyspnea; cough; sputum.
Nighttime sleep disruption is characteristic of long-term care residents, is typically accompanied by daytime sleepiness and may be caused by a multitude of factors. Causal factors include medical and psychiatric illness, medications, circadian rhythm abnormalities, sleep disordered breathing and other primary sleep disorders, environmental factors and lifestyle habits. There is some suggestion that these factors are amenable to treatment; however, further research on the implementation of treatments within the long-term care setting is needed. Additional work is also needed to understand the administrative and policy factors that might lead to systemic changes in how sleep is viewed and sleep problems are addressed in long-term care settings.
A growing number of older adults reside in long-term care facilities. In this setting, residents commonly suffer from nighttime sleep disruption, which is often accompanied by daytime sleepiness and may be caused by a multitude of factors. Importantly, sleep disturbance is associated with negative health outcomes, including risk for falling, and elevated mortality risk among long-term care residents. A number of factors contribute to sleep disturbance in the long-term care setting including medical and psychiatric illness, medications, circadian rhythm abnormalities, sleep disordered breathing and other primary sleep disorders, environmental conditions (e.g., noise and light) and lifestyle habits. Based on research with older adults in the community and work conducted within long-term care settings, there is some suggestion that these factors are amenable to nonpharmacological treatments. Further research on the broad implementation of treatments for sleep problems within the long-term care setting is still needed. Additional work is also needed to understand the administrative and policy factors that might lead to systemic changes in how sleep is viewed and sleep problems are addressed in long-term care settings.
long; term care; dementia; circadian rhythms; sleep disorders
Sleep disruption is common in the long-term care setting. This paper discusses the available literature on two herbal approaches to sleep problems in long-term care. The largest body of evidence exists for the use of the dietary/herbal supplements valerian and melatonin. While these agents appear to have a modest positive effect on sleep quality among older adults, most studies were small in size and included only subjective assessments of sleep quality. In addition, it is unclear whether these agents pose risks to long-term care residents due to potential drug interactions. Additional research is needed prior to making conclusive recommendations about the use of these interventions for sleep in the long-term care setting.
alternative therapies; elderly; insomnia; sleep
With increased governmental interest in value assessment of technologies and where medical device manufacturers are finding it increasingly necessary to become more familiar with economic evaluation methods, the study sought to explore the levels of health economics knowledge within small and medium-sized enterprises (SMEs) and to scope strategies they employ to demonstrate the value of their products to purchasers.
A short questionnaire was completed by participants attending one of five workshops on product development in the medical device sector that took place in England between 2007 and 2011. From all responses obtained, a large proportion of participants were based in SMEs (N = 43), and these responses were used for the analysis. Statistical analysis using non-parametric tests was performed on questions with approximately interval scales. Qualitative data from participant responses were analysed to reveal emerging themes.
The questionnaire results revealed that 60% of SME participants (mostly company directors or managers, including product or project managers) rated themselves as having low or no knowledge of health economics prior to the workshops but the rest professed at least medium knowledge. Clinical trials and cost analyses or cost-effectiveness studies were the most highly cited means by which SMEs aim to demonstrate value of products to purchasers. Purchasers were perceived to place most importance on factors of safety, expert opinion, cost-effectiveness and price. However many companies did not utilise formal decision-making tools to prioritise these factors. There was no significant dependence of the use of decision-making tools in general with respect to professed knowledge of health economics methods. SMEs did not state a preference for any particular aspect of potential value when deciding whether to develop a product. A majority of SMEs stated they would use a health economics tool. Research and development teams or marketing and sales departments would most likely use one.
This study points to the need for further research into the education requirements of SMEs in the area of Health Technology Assessment (HTA) and also for investigation into how SMEs engage with existing HTA processes as required by assessors such as NICE.
It is well established that considering users is an important aspect of medical device development. However it is also well established that there are numerous barriers to successfully conducting user research and integrating the results into product development. It is not sufficient to simply conduct user research, it must also be effectively integrated into product development.
A case study of the development of a new medical imaging device was conducted to examine in detail how users were involved in a medical device development project. Two user research studies were conducted: a requirements elicitation interview study and an early prototype evaluation using contextual inquiry. A descriptive in situ approach was taken to investigate how these studies contributed to the product development process and how the results of this work influenced the development of the technology. Data was collected qualitatively through interviews with the development team, participant observation at development meetings and document analysis. The focus was on investigating the barriers that exist to prevent user data from being integrated into product development.
A number of individual, organisational and system barriers were identified that functioned to prevent the results of the user research being fully integrated into development. The user and technological aspects of development were seen as separate work streams during development. The expectations of the developers were that user research would collect requirements for the appearance of the device, rather than challenge its fundamental concept. The manner that the user data was communicated to the development team was not effective in conveying the significance or breadth of the findings.
There are a range of informal and formal organisational processes that can affect the uptake of user data during medical device development. Adopting formal decision making processes may assist manufacturers to take a more integrated and reflective approach to development, which should result in improved business decisions and a higher quality end product.
Medical device; Product development; User centred-design
To determine seniors’ beliefs about falls and design a fall-risk self-assessment and educational materials to promote early identification of evidence-based fall risks and encourage prevention behaviors.
Focus groups with community-dwelling seniors, conducted in two phases to identify perceptions about fall risks and risk reduction and to assess face validity of the fall-risk self-assessment and acceptability of educational materials.
Lay perception of fall risks was in general concordance with evidence-based research. Maintaining independence and positive tone were perceived as key motivators for fall prevention. Seniors intended to use information in the educational tool to stimulate discussions about falls with health care providers.
An evidence-based, educational fall-risk self-assessment acceptable to older adults can build on existing lay knowledge about fall risks and perception that falls are a relevant problem and can educate seniors about their specific risks and how to minimize them.
falls; qualitative research methods; preventive medicine; preventive care; preventive services
Excessive daytime sleeping is associated with poorer functional outcomes in rehabilitation populations and may be improved with targeted interventions. The purpose of this study was to test simple methods of screening for excessive daytime sleeping among older adults admitted for post-acute rehabilitation.
Secondary analysis of data from two clinical samples.
Two post-acute rehabilitation (PAR) units in southern California.
Two hundred twenty-six patients aged > 65 years with Mini-Mental State Examination (MMSE) score > 11 undergoing rehabilitation.
The primary outcome was excessive daytime sleeping, defined as greater than 15% (1.8 hours) of daytime hours (8AM to 8PM) sleeping as measured by actigraphy.
Participants spent, on average, 16.2% (SD 12.5%) of daytime hours sleeping as measured by actigraphy. Thirty nine percent of participants had excessive daytime sleeping. The Pittsburgh Sleep Quality Index (PSQI) was significantly associated with actigraphically-measured daytime sleeping (p= 0.0038), but the Epworth Sleepiness Scale (ESS) was not (p = 0.49). Neither the ESS nor the PSQI achieved sufficient sensitivity and specificity to be used as a screening tool for excessive daytime sleeping. Two additional models using items from these questionnaires were not significantly associated with the outcome.
In an older PAR population, self-report items from existing sleep questionnaires do not identify excessive daytime sleeping. Therefore we recommend objective measures for the evaluation of excessive daytime sleeping as well as further research to identify new self-report items that may be more applicable in PAR populations.
sleep; post-acute care; rehabilitation; screen
In the Gulf of Maine area (GoMA), as elsewhere in the ocean, the organisms of greatest numerical abundance are microbes. Viruses in GoMA are largely cyanophages and bacteriophages, including podoviruses which lack tails. There is also evidence of Mimivirus and Chlorovirus in the metagenome. Bacteria in GoMA comprise the dominant SAR11 phylotype cluster, and other abundant phylotypes such as SAR86-like cluster, SAR116-like cluster, Roseobacter, Rhodospirillaceae, Acidomicrobidae, Flavobacteriales, Cytophaga, and unclassified Alphaproteobacteria and Gammaproteobacteria clusters. Bacterial epibionts of the dinoflagellate Alexandrium fundyense include Rhodobacteraceae, Flavobacteriaceae, Cytophaga spp., Sulfitobacter spp., Sphingomonas spp., and unclassified Bacteroidetes. Phototrophic prokaryotes in GoMA include cyanobacteria that contain chlorophyll (mainly Synechococcus), aerobic anoxygenic phototrophs that contain bacteriochlorophyll, and bacteria that contain proteorhodopsin. Eukaryotic microalgae in GoMA include Bacillariophyceae, Dinophyceae, Prymnesiophyceae, Prasinophyceae, Trebouxiophyceae, Cryptophyceae, Dictyochophyceae, Chrysophyceae, Eustigmatophyceae, Pelagophyceae, Synurophyceae, and Xanthophyceae. There are no records of Bolidophyceae, Aurearenophyceae, Raphidophyceae, and Synchromophyceae in GoMA. In total, there are records for 665 names and 229 genera of microalgae. Heterotrophic eukaryotic protists in GoMA include Dinophyceae, Alveolata, Apicomplexa, amoeboid organisms, Labrynthulida, and heterotrophic marine stramenopiles (MAST). Ciliates include Strombidium, Lohmaniella, Tontonia, Strobilidium, Strombidinopsis and the mixotrophs Laboea strobila and Myrionecta rubrum (ex Mesodinium rubra). An inventory of selected microbial groups in each of 14 physiographic regions in GoMA is made by combining information on the depth-dependent variation of cell density and the depth-dependent variation of water volume. Across the entire GoMA, an estimate for the minimum abundance of cell-based microbes is 1.7×1025 organisms. By one account, this number of microbes implies a richness of 105 to 106 taxa in the entire water volume of GoMA. Morphological diversity in microplankton is well-described but the true extent of taxonomic diversity, especially in the femtoplankton, picoplankton and nanoplankton – whether autotrophic, heterotrophic, or mixotrophic, is unknown.
A C-terminal fragment of VERNALIZATION1 from A. thaliana, a DNA-binding protein required for the acceleration of flowering in response to prolonged cold treatment, was crystallized. X-ray diffraction data were collected to a resolution of 2.1 Å.
VERNALIZATION1 (VRN1) is required in the model plant Arabidopsis thaliana for the epigenetic suppression of the floral repressor FLC by prolonged cold treatment. Stable suppression of FLC accelerates flowering, a physiological process known as vernalization. VRN1 is a 341-residue DNA-binding protein that contains two plant-specific B3 domains (B3a and B3b), a putative nuclear localization sequence (NLS) and two putative PEST domains. VRN1208–341 includes the second B3 domain and a region upstream that is highly conserved in the VRN1 orthologues of other dicotyledonous plants. VRN1208–341 was crystallized by the hanging-drop method in 0.05 M sodium acetate pH 6.0 containing 1.0 M NaCl and 18%(w/v) PEG 3350. Preliminary X-ray diffraction data analysis revealed that the VRN1208–341 crystal diffracted to 2.1 Å and belonged to space group C2, with unit-cell parameters a = 105.2, b = 47.9, c = 61.2 Å, α = 90.0, β = 115.4, γ = 90.0°. Assuming that two molecules occupy the asymmetric unit, a Matthews coefficient of 2.05 Å3 Da−1 and a solvent content of 40.1% were calculated.
vernalization; B3 domain; DNA binding; chromatin; epigenetic suppression; Arabidopsis thaliana
Academic literature and international standards bodies suggest that user involvement, via the incorporation of human factors engineering methods within the medical device design and development (MDDD) process, offer many benefits that enable the development of safer and more usable medical devices that are better suited to users' needs. However, little research has been carried out to explore medical device manufacturers' beliefs and attitudes towards user involvement within this process, or indeed what value they believe can be added by doing so.
In-depth interviews with representatives from 11 medical device manufacturers are carried out. We ask them to specify who they believe the intended users of the device to be, who they consult to inform the MDDD process, what role they believe the user plays within this process, and what value (if any) they believe users add. Thematic analysis is used to analyse the fully transcribed interview data, to gain insight into medical device manufacturers' beliefs and attitudes towards user involvement within the MDDD process.
A number of high-level themes emerged, relating who the user is perceived to be, the methods used, the perceived value and barriers to user involvement, and the nature of user contributions. The findings reveal that despite standards agencies and academic literature offering strong support for the employment formal methods, manufacturers are still hesitant due to a range of factors including: perceived barriers to obtaining ethical approval; the speed at which such activity may be carried out; the belief that there is no need given the 'all-knowing' nature of senior health care staff and clinical champions; a belief that effective results are achievable by consulting a minimal number of champions. Furthermore, less senior health care practitioners and patients were rarely seen as being able to provide valuable input into the process.
Medical device manufacturers often do not see the benefit of employing formal human factors engineering methods within the MDDD process. Research is required to better understand the day-to-day requirements of manufacturers within this sector. The development of new or adapted methods may be required if user involvement is to be fully realised.
Behavioral scientists have increasingly included inflammatory biology as mechanisms in their investigation of psychosocial dynamics on the pathobiology of disease. However, a lack of standardization of inclusion and exclusion criteria and assessment of relevant control variables impacts the interpretation of these studies. The present paper reviews and discusses human biobehavioral factors that can affect the measurement of circulating markers of inflammation. Keywords relevant to inflammatory biology and biobehavioral factors were searched through PubMed. Age, sex, and hormonal status, socioeconomic status, ethnicity and race, body mass index, exercise, diet, caffeine, smoking, alcohol, sleep disruption, antidepressants, aspirin, and medications for cardiovascular disease are all reviewed. A tiered set of recommendations as to whether each variable should be assessed, controlled for, or used as an exclusion criteria is provided. These recommendations provide a framework for observational and intervention studies investigating linkages between psychosocial and behavioral factors and inflammation.
Patients with Alzheimer’s dementia often display both agitated behavior and poor sleep. Given that the disease is often associated with low endogenous levels of melatonin, exogenous melatonin administration may lead to improvements in sleep and agitation.
Randomized, placebo-controlled study.
Nursing homes in San Diego metropolitan area.
Subjects were patients with probable Alzheimer’s disease.
Melatonin (8.5 mg immediate release and 1.5 mg sustained release) (n=24) or placebo (n=17) administered at 10:00 PM for 10 consecutive nights. The protocol consisted of baseline (3 days), treatment (10 days), and post-treatment (5 days) phases.
Sleep was measured continuously using actigraphy. Agitation was rated using both the Agitated Behavior Rating Scale and the Cohen-Mansfield Agitation Inventory. Treatment effects were examined both across the 24-hour day and separately by nursing shift.
There were no significant effects of melatonin, compared to placebo, on sleep, circadian rhythms, or agitation.
This study failed to find a beneficial effect of exogenous melatonin, consistent with a number of other studies. The lack of efficacy may be related to the absence of a true treatment effect or to the super-physiological dose of melatonin used.
Alzheimer’s; sleep; agitation; melatonin; dementia
Protein crystallisation screening involves the parallel testing of large numbers of candidate conditions with the aim of identifying conditions suitable as a starting point for the production of diffraction quality crystals. Generally, condition screening is performed in 96-well plates. While previous studies have examined the effects of protein construct, protein purity, or crystallisation condition ingredients on protein crystallisation, few have examined the effect of the crystallisation plate.
We performed a statistically rigorous examination of protein crystallisation, and evaluated interactions between crystallisation success and plate row/column, different plates of same make, different plate makes and different proteins. From our analysis of protein crystallisation, we found a significant interaction between plate make and the specific protein being crystallised.
Protein crystal structure determination is the principal method for determining protein structure but is limited by the need to produce crystals of the protein under study. Many important proteins are difficult to crystallise, so that identification of factors that assist crystallisation could open up the structure determination of these more challenging targets. Our findings suggest that protein crystallisation success may be improved by matching a protein with its optimal plate make.
To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light.
Randomized controlled trial.
Two San Diego–area nursing homes.
Seventy-seven (58 women, 19 men) nursing home residents participated. Mean age ± standard deviation was 85.7 ± 7.3 (range 60–100) and mean Mini-Mental State Examination was 12.8 ± 8.8 (range 0–30).
Participants were assigned to one of four treatments: evening bright light, morning bright light, daytime sleep restriction, or evening dim red light.
Improvement in nighttime sleep quality, daytime alertness, and circadian activity rhythm parameters.
There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups. Morning bright light delayed the peak of the activity rhythm (acrophase) and increased the mean activity level (mesor). In addition, subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment.
Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust. These changes have the potential to be clinically beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable.
dementia; sleep; light; circadian rhythms; nursing home; older
Cocrystallization with a peptide, free-interface diffusion crystal chips and crystal dehydration were important in the production of diffraction-quality crystals of the Munc18c protein that helps to regulate membrane fusion.
The production of diffraction-quality crystals of Munc18c, a protein involved in regulating vesicular exocytosis in mammals, is reported. The diffraction resolution of Munc18c crystals was optimized by (i) cocrystallizing with a peptide fragment of the Munc18c functional binding partner syntaxin4, (ii) using nanolitre free-interface diffusion crystallization-screening chips and microlitre hanging-drop vapour diffusion and (iii) applying a post-crystallization dehydration treatment. Crystals belonging to the cubic space group P213, with unit-cell parameters a = b = c = 170.8 Å, α = β = γ = 90°, were generated that diffract to 3.7 Å resolution on a laboratory X-ray source.
Munc18c; syntaxin4; free-interface diffusion; dehydration