Crystallography of honeycomb formation under geometric frustration.

As honeybees build their nests in preexisting tree cavities, they must deal with the presence of geometric constraints, resulting in nonregular hexagons and topological defects in the comb. In this work, we study how bees adapt to their environment in order to regulate the comb structure. Specifically, we identify the irregularities in honeycomb structure in the presence of various geometric frustrations. We 3D-print experimental frames with a variety of constraints imposed on the imprinted foundations. The combs constructed by the bees show clear evidence of recurring patterns in response to specific geometric frustrations on these starter frames. Furthermore, using an experimental-modeling framework, we demonstrate that these patterns can be successfully modeled and replicated through a simulated annealing process, in which the minimized potential is a variation of the Lennard-Jones potential that considers only first-neighbor interactions according to a Delaunay triangulation. Our simulation results not only confirm the connection between honeycomb structures and other crystal systems such as graphene, but also show that irregularities in the honeycomb structure can be explained as the result of analogous interactions between cells and their immediate surroundings, leading to emergent global order. Additionally, our computational model can be used as a first step to describe specific strategies that bees use to effectively solve geometric mismatches while minimizing cost of comb building.

Effectiveness of a mindfulness intervention for older adults to improve emotional well-being and cognitive function in a Chinese population: A randomized waitlist-controlled trial.

BACKGROUND: To investigate the effect of a modified mindfulness-based stress reduction (mMBSR) program on mental well-being and cognitive function of older adults. METHOD: Two hundred and fourty-six participants were randomly assigned to mMBSR (n = 120) group or waitlist control group which received mMBSR at 2-month (n = 123). Data collected at baseline, 2 and 4 months after recruitment. PRIMARY OUTCOME: mental well-being: Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS). SECONDARY OUTCOMES: Five Facet Mindfulness Questionnaire Short Form, Montreal Cognitive Assessment (MOCA), Verbal Fluency Test (VFT), international shopping list test, self-compassion scale, peace of mind scale, geriatric depression scale (GDS), and Pittsburgh sleep quality index (PSQI). In modified-intention-to-treat analysis, paired t-test for within group comparison, and ANCOVA to compare group differences at 2-months with adjustment of baseline values. RESULTS: Most participants were female (83.7%), living with others (67.0%), and married (50.7%). No significant difference of baseline characteristics except sleep quality. At 2 months, intervention group reported better mental well-being (0.9, 95%CI: 0.1-1.8, p = 0.025) and less depressive symptoms (-1.0; 95%CI: -1.7 to -0.3, p = 0.004). Within group at 2 months, intervention group had improvement in: mental well-being (SWEMWBS: 22.5-23.4, p = 0.011), cognitive function (MOCA: 24.6-25.8, p < 0.001; VFT: 38.7-42.1, p < 0.001), depressive symptoms (GDS: 4.1-3.1, p < 0.001), and sleep quality (PSQI: 8.3-6.7, p < 0.001). All these changes, except mental well-being, were sustained at 4 months. DISCUSSION: Attrition rate was 14% and mindfulness intervention was found to be feasible and acceptable in older adults. Major limitation of the study was the absence of an active control group to control for non-specific effect.

Clinic-Based Patellar Mobilization Therapy for Knee Osteoarthritis: A Randomized Clinical Trial.

PURPOSE: We performed a phase 2 randomized clinical trial to evaluate the preliminary effectiveness of a clinic-based patellar mobilization therapy (PMT) in patients with knee osteoarthritis. METHODS: We recruited 208 patients with knee osteoarthritis at primary care clinics in Hong Kong. Patients were randomly assigned (1:1) to the intervention group or the control group. The intervention group received 3 PMT treatment sessions from primary care physicians at 2-month intervals, with concomitant prescription of a home-based vastus medialis oblique muscle exercise. The control group received PMT after the study period. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Secondary outcomes included the WOMAC composite, function, and stiffness scores; the visual analog scale score for pain; objective physical function tests (30-s chair stand, 40-m walk test, timed up and go test, and EuroQol-5D). All outcomes were evaluated at baseline and at 24 weeks through intention-to-treat analysis. RESULTS: We observed no baseline between-group differences. The WOMAC pain score showed greater improvement in the intervention group than in the control group at 24 weeks (between-group difference - 15.6, 95% CI, - 20.5 to - 10.7, P <.001). All secondary outcomes also demonstrated significant between-group differences. CONCLUSIONS: Patellar mobilization therapy has the potential to reduce pain and improve function and quality of life for patients with knee osteoarthritis. Future clinical trials with comparison to other active comparator controls will help determine the overall efficacy and facilitate the deployment of PMT in real-world practice.

Exercise Intervention to Normalize Blood Pressure and Nocturnal Dipping in HyperTensive Patients (END-HT): Protocol of a Randomized Controlled Trial.

BACKGROUND: Lack of decrease (≤10%) in systolic blood pressure (BP) during sleep, referred to as non-dipping (ND), independently predicts cardiovascular events and mortality. There has been no prospective and adequately powered randomized controlled trial (RCT) to determine whether exercise, when compared with standard treatment, can normalize ND in patients with hypertension (HT). Further, most patients do not sustain an exercise program by 12 months. METHODS: A 2-arm, assessor-blinded RCT, involving 198 hypertensive Chinese patients who have ND will be conducted to evaluate the effectiveness of a combined exercise (aerobic exercise and resistance training) program to normalize ND. The combined exercise program, "exercise is medicine" (EIM), was developed to maintain exercise habit using a variety of techniques (e.g. 12-week exercise classes, mobile application, wrist trackers, self-scheduling, monitoring, regular feedback, and motivational interviewing). Eligible patients will be randomized to EIM plus usual care or to usual care in 1:1 ratio by stratified randomization according to age and sex. The randomization sequence is blinded to the investigators and allocation is disclosed only after valid consent. Ambulatory BP measurements will be performed at baseline, 3, and 12 months. The primary outcome is proportion of participants with ND at 3 months; secondary outcomes include proportion of participants with ND at 12 months, absolute BP values at 3 and 12 months. Exercise level will be detected by validated questionnaire and compared between 2 arms at 3 and 12 months. CONCLUSION: The trial will examine the efficacy of treating ND and HT by an exercise program.

Intra-articular and extra-articular platelet-rich plasma injections for knee osteoarthritis: A 26-week, single-arm, pilot feasibility study.

AIM: Platelet Rich Plasma (PRP) is an emerging therapy for knee osteoarthritis (KOA). Studies have evaluated the effectiveness of intra-articular PRP, which ignores extra-articular tissue dysfunction and may provide incomplete treatment of KOA. The study aimed to pilot test a leukocyte-rich (mononuclear cells) PRP injection protocol for primary KOA, which consisted of single intra-articular injection and extra-articular injections on the medial coronary and medial collateral ligaments. METHODS: A prospective 26-week single-arm uncontrolled feasibility pilot study. Patients (N = 12) with primary KOA as defined by the American Rheumatology Association, with moderate to severe medial knee pain which failed conservative management, were recruited in a university primary care clinic and received a single session of PRP injection in week 1. The primary outcome was the feasibility of the protocol at 26 weeks as defined by rates of recruitment, compliance, retention, dropout, side effects or adverse events; and treatment satisfaction. Secondary outcomes included the Western Ontario McMaster University Osteoarthritis Index, the Intermittent and Constant Osteoarthritis Pain total and subscales, objective physical function tests and EuroQol-5D. RESULTS: Twelve of 40 potential patients were recruited in 3 months period (recruitment rate 30%, x2 = 3.33, P = 0.068). All participants adhered to the protocol and completed the follow up assessment with no dropouts (dropout rate 0%, X2= 2.67, P = 0.103). Satisfaction was high; no related adverse events were reported. Most secondary outcomes showed statistically significant improvement. CONCLUSIONS: Concomitant intra-articular and extra-articular PRP injections were feasible and produced preliminary favourable outcomes.

Clinical effectiveness of patella mobilisation therapy versus a waiting list control for knee osteoarthritis: a protocol for a pragmatic randomised clinical trial.

INTRODUCTION: Knee osteoarthritis (KOA) is a common, disabling and costly medical condition. The patellofemoral joint is a critical source of pain in individuals with KOA, and coexistence of patellofemoral osteoarthritis (PFOA) and tibiofemoral osteoarthritis (TFOA) is sometimes observed. The identification of subgroups with PFOA and customised interventions to correct underlying pathomechanics is beneficial for individuals with KOA. This study aims to evaluate whether a clinic-based patella mobilisation therapy (PMT) leads to significant improvement in pain, physical function and quality of life of individuals with KOA. METHODS AND ANALYSIS: A total of 208 participants with coexistence of PFOA and TFOA will be recruited. A pragmatic randomised clinical trial will be conducted, and participants will be randomised into the PMT and waiting list groups. For the PMT group, three manual mobilisation sessions, along with home-based vastus medialis oblique muscle exercise, will be conducted at 2-month intervals. The waiting list group will continue to receive their usual care, and as an incentive the waiting list group will be offered PMT after the study period is over. The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, and secondary outcomes include the WOMAC function and stiffness subscales, scores for objective physical function tests (the 30 s chair stand, 40-metre fast-paced walk test, the Timed Up and Go Test), and the EuroQol-5D scores. All outcomes will be evaluated at baseline and 6 months using intention-to-treat and incorporating covariate analysis. ETHICS AND DISSEMINATION: Ethics approval has been obtained (CREC no: 2014.379). Results of the trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR-IPC-15006618; Pre-results.

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review.

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59-0.90% and 0.77-1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups.

Exposure to air pollutants and mortality in hypertensive patients according to demography: a 10 year case-crossover study.

This study evaluated whether short term exposures to NO2, O3, particulate matter <10 mm in diameter (PM10) were associated with higher risk of mortality. A total of 223,287 hypertensive patients attended public health-care services and newly prescribed at least 1 antihypertensive agent were followed-up for up to 5 years. A time-stratified, bi-directional case-crossover design was adopted. For all-cause mortality, significant positive associations were observed for NO2 and PM10 at lag 0-3 days per 10 µg/m(3) increase in concentration (excess risks 1.187%-2.501%). Significant positive associations were found for O3 at lag 1 and 2 days and the excess risks were 1.654% and 1.207%, respectively. We found similarly positive associations between these pollutants and respiratory disease mortality. These results were significant among those aged ≥65 years and in cold seasons only. Older hypertensive patients are susceptible to all-cause and respiratory disease-specific deaths from these air pollutants in cold weather.

Do deviations from bond enthalpy additivity define the thermodynamic stabilities of diradicals?

Deviations from bond enthalpy additivity (DeltaBEA) are frequently used to assess the thermodyamic stabilities of diradicals. (U)B3LYP/6-31G calculations have been performed in order to determine how well DeltaBEA values actually do reflect the thermodynamic stabilities of the triplet states of diradicals in which one or both nonbonding electrons occupy a delocalized pi orbital. The calculations find that different pathways for forming sigma,pi-diradicals, such as alpha,2- and alpha,4-dehydrotoluene (4 and 6), give DeltaBEA values that differ by ca. 1 kcal/mol. The path dependency of the DeltaBEA values is computed to be one order of magnitude larger for non-Kekulé hydrocarbon diradicals, such as m-benzoquinodimethane (12) and 1,3-dimethylenecyclobutane-2,4-diyl (15), than for sigma,pi-diradicals. Since the DeltaBEA values for forming 4, 6, 12, and 15 are all path dependent, we conclude that DeltaBEA values for diradicals with one or two delocalized, nonbonding pi electrons do not, in general, uniquely define the thermodynamic stabilities of the diradicals. Hence, DeltaBEA values should not be used for this purpose, especially for non-Kekulé hydrocarbon diradicals.

Between geometry, stability, and polarizability: density functional theory studies of silicon clusters Sin (n = 3-10).

The relationship between the polarizability, stability, and the geometry of small-size silicon clusters has been investigated by the density functional theory methods. Results obtained at local density approximation/Vosko-Wilk-Nusair and general gradient approximation/BLYP levels with polarized even-tempered basis set of quadruple zeta quality are presented and compared with those obtained by the B3LYP method, as well as with the ab initio results in recent literature. We have found that the polarizability is directly related to the size of the energy gap between symmetry-compatible bonding and antibonding molecular orbitals, but not necessarily to the size of the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gap. Furthermore, we have defined two structural parameters, namely, the averaged Si-Si distances and the standard deviation of the Si-Si distances, which were found to correlate remarkably well with the binding energy of the clusters and the HOMO-LUMO gap, respectively. These straightforward correlations would, therefore, provide a means to predict the physical properties, in particular, the polarizability and the stability, simply based on the structural information of the cluster.

DFT calculations on the effects of para substituents on the energy differences between singlet and triplet states of 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls.

UB3LYP/6-31g* calculations have been performed on a series of para-substituted 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls (4). The singlet is computed to be the ground state for each of the diradicals, regardless of the nature of the para substituents, which range from strongly pi-electron-donating (amino) to strongly pi-electron-withdrawing (nitro). In the symmetrically para-disubstituted diradicals, the size of the singlet-triplet energy gap (Delta E(ST)) increases with the pi-electron-donating ability of the substituents, but in the unsymmetrically substituted diradicals, large values of Delta E(ST) are calculated even when one of the substituents is a pi electron acceptor. The origins of the competitive and cooperative substituent effects, predicted for diradical 4, are discussed in light of the calculated effects of the same substituents on the singlet and triplet states of diradical 6, which lacks the geminal fluorines at C-2 that are present in 4.