Perceived Limitations of Walking in Individuals With Cerebral Palsy.

OBJECTIVE: Impairments associated with cerebral palsy (CP) can affect gait quality and limit activity and participation. The purpose of this study was to quantify (1) which of 6 factors (pain, weakness, endurance, mental ability, safety concerns, balance) were perceived to limit walking ability the most in individuals with CP and (2) whether age or Gross Motor Function Classification System (GMFCS) level is related to that perception. METHODS: This cross-sectional study queried data from a gait laboratory database. Perceived walking limitation was quantified using a 5-point Likert scale ("never" to "all of the time"). Included were 1566 children and adults (mean age = 10.9 y [SD = 6.8]; range = 3.0-72.1 y) with CP (GMFCS level I: 502; II: 564; III: 433; IV: 67). RESULTS: Patients or caregivers perceived balance to limit walking ability to the greatest extent, followed by endurance, weakness, safety, mental ability, and pain. Balance was perceived to always limit walking ability in 8%, 22%, 30%, and 34% of individuals in GMFCS levels I through IV, respectively. Endurance was perceived to always limit walking ability in 5%, 13%, 13%, and 27% of individuals in GMFCS levels I through IV, respectively. There were minor differences in the perceived extent of limitation caused by the factors by GMFCS level. Only weak associations between age and pain, mental ability, safety, and balance were observed (Spearman rho = -0.13 to 0.24). CONCLUSION: Patients or caregivers perceived decreased balance and endurance to most strongly limit walking ability. Efforts should be made to clinically track how both perceived and objective measures of these limiting factors change with age and intervention. IMPACT: Following a patient- and family-centered care model, therapy that places greater emphasis on balance and cardiovascular endurance may have the greatest effect on walking ability for individuals with CP. Future research should quantify which therapeutic, surgical, and pharmacologic interventions minimize these impairments and optimize activity and participation. LAY SUMMARY: Balance and endurance are perceived to be the greatest factors limiting walking in people with CP. If you have CP, your physical therapist might emphasize balance and cardiovascular endurance to improve your walking ability.

An operando spatially resolved study of alkaline battery discharge using a novel hyperspectral detector and X-ray tomography.

An experimental technique is described for the collection of time-resolved X-ray diffraction information from a complete commercial battery cell during discharging or charging cycles. The technique uses an 80 × 80 pixel 2D energy-discriminating detector in a pinhole camera geometry which can be used with a polychromatic X-ray source. The concept was proved in a synchrotron X-ray study of commercial alkaline Zn-MnO2 AA size cells. Importantly, no modification of the cell was required. The technique enabled spatial and temporal changes to be observed with a time resolution of 20 min (5 min of data collection with a 15 min wait between scans). Chemical changes in the cell determined from diffraction information were correlated with complementary X-ray tomography scans performed on similar cells from the same batch. The clearest results were for the spatial and temporal changes in the Zn anode. Spatially, there was a sequential transformation of Zn to ZnO in the direction from the separator towards the current collector. Temporally, it was possible to track the transformation of Zn to ZnO during the discharge and follow the corresponding changes in the cathode.

Clinician preferences for computerised clinical decision support for medications in primary care: a focus group study.

BACKGROUND: To improve user-centred design efforts and efficiency; there is a need to disseminate information on modern day clinician preferences for technologies such as computerised clinical decision support (CDS). OBJECTIVE: To describe clinician perceptions regarding beneficial features of CDS for chronic medications in primary care. METHODS: This study included focus groups and clinicians individually describing their ideal CDS. Three focus groups were conducted including prescribing clinicians from a variety of disciplines. Outcome measures included identification of favourable features and unintended consequences of CDS for chronic medication management in primary care. We transcribed recordings, performed thematic qualitative analysis and generated counts when possible. RESULTS: There were 21 participants who identified four categories of beneficial CDS features during the group discussion: non-interruptive alerts, clinically relevant and customisable support, presentation of pertinent clinical information and optimises workflow. Non-interruptive alerts were broadly defined as passive alerts that a user chooses to review, whereas interruptive were active or disruptive alerts that interrupted workflow and one is forced to review before completing a task. The CDS features identified in the individual descriptions were consistent with the focus group discussion, with the exception of non-interruptive alerts. In the individual descriptions, 12 clinicians preferred interruptive CDS compared with seven clinicians describing non-interruptive CDS. CONCLUSION: Clinicians identified CDS for chronic medications beneficial when they are clinically relevant and customisable, present pertinent clinical information (eg, labs, vitals) and improve their workflow. Although clinicians preferred passive, non-interruptive alerts, most acknowledged that these may not be widely seen and may be less effective. These features align with literature describing best practices in CDS design and emphasise those features clinicians prioritise, which should be considered when designing CDS for medication management in primary care. These findings highlight the disparity between the current state of CDS design and clinician-stated design features associated with beneficial CDS.

Prescribing attitudes, behaviors and opinions regarding metformin for patients with diabetes: a focus group study.

BACKGROUND: The purpose of this study was to identify the reasons why metformin prescribing is suboptimal. METHODS: Two semi-structured focus groups with attitudinal questionnaires and a brief educational presentation were held in two US cities. Participants included providers (physicians, pharmacists, midlevel practitioners) caring for patients with type 2 diabetes mellitus (T2DM) in an ambulatory setting. Outcome measures included provider attitudes, behaviors and opinions regarding the use of metformin. RESULTS: Participants identified three main themes influencing the use of metformin, including the appropriate timing of metformin initiation, known risks associated with metformin, and procedures to manage safety concerns and mitigate adverse effects associated with metformin. Participant prescribing behaviors of metformin were not consistent with the best available evidence in the settings of renal insufficiency, heart failure, hepatic dysfunction, alcohol use, and lactic acidosis. With minimal education, provider prescribing behaviors appeared to change by the end of the focus group to align more closely with the best available evidence. CONCLUSIONS: Provider attitudes, behaviors and opinions regarding the use of metformin for T2DM reveals the need for further education to improve appropriate use of metformin. Educational interventions should target prescribing behaviors and opinions identified to be inconsistent with the evidence.

Shiga Toxin 1-Producing Shigella sonnei Infections, California, United States, 2014-2015.

Shiga toxins (Stx) are primarily associated with Shiga toxin-producing Escherichia coli and Shigella dysenteriae serotype 1. Stx production by other shigellae is uncommon, but in 2014, Stx1-producing S. sonnei infections were detected in California. Surveillance was enhanced to test S. sonnei isolates for the presence and expression of stx genes, perform DNA subtyping, describe clinical and epidemiologic characteristics of case-patients, and investigate for sources of infection. During June 2014-April 2015, we identified 56 cases of Stx1-producing S. sonnei, in 2 clusters. All isolates encoded stx1 and produced active Stx1. Multiple pulsed-field gel electrophoresis patterns were identified. Bloody diarrhea was reported by 71% of case-patients; none had hemolytic uremic syndrome. Some initial cases were epidemiologically linked to travel to Mexico, but subsequent infections were transmitted domestically. Continued surveillance of Stx1-producing S. sonnei in California is necessary to characterize its features and plan for reduction of its spread in the United States.

Aptamer ARC19499 mediates a procoagulant hemostatic effect by inhibiting tissue factor pathway inhibitor.

Hemophilia A and B are caused by deficiencies in coagulation factor VIII (FVIII) and factor IX, respectively, resulting in deficient blood coagulation via the intrinsic pathway. The extrinsic coagulation pathway, mediated by factor VIIa and tissue factor (TF), remains intact but is negatively regulated by tissue factor pathway inhibitor (TFPI), which inhibits both factor VIIa and its product, factor Xa. This inhibition limits clot initiation via the extrinsic pathway, whereas factor deficiency in hemophilia limits clot propagation via the intrinsic pathway. ARC19499 is an aptamer that inhibits TFPI, thereby enabling clot initiation and propagation via the extrinsic pathway. The core aptamer binds tightly and specifically to TFPI. ARC19499 blocks TFPI inhibition of both factor Xa and the TF/factor VIIa complex. ARC19499 corrects thrombin generation in hemophilia A and B plasma and restores clotting in FVIII-neutralized whole blood. In the present study, using a monkey model of hemophilia, FVIII neutralization resulted in prolonged clotting times as measured by thromboelastography and prolonged saphenous-vein bleeding times, which are consistent with FVIII deficiency. ARC19499 restored thromboelastography clotting times to baseline levels and corrected bleeding times. These results demonstrate that ARC19499 inhibition of TFPI may be an effective alternative to current treatments of bleeding associated with hemophilia.

Healers in a non-traditional role; a focus group study of Sangoma's knowledge of and attitudes to cervical cancer prevention and screening in Johannesburg, South Africa.

Twelve Sangomas or traditional healers participated in a focus group exploring their understanding of cervical cancer and human papilloma virus (HPV), their role informing women about cervical cancer prevention and screening; and their interaction/cooperation with western medicine. Participants lacked knowledge of HPV and the HPV vaccine but had an understanding of cervical cancer prevention and pap smears. Participants expressed interest in greater collaboration with western doctors, requested more prevention information, and noted the vaccine could serve as strategy to prevent HPV in victims of sexual violence, and time of vaccination could serve as an opportunity for parents to talk to their children about sex.

Hammerhead redux: does the new structure fit the old biochemical data?

The cleavage rates of 78 hammerhead ribozymes containing structurally conservative chemical modifications were collected from the literature and compared to the recently determined crystal structure of the Schistosoma mansoni hammerhead. With only a few exceptions, the biochemical data were consistent with the structure, indicating that the new structure closely resembles the transition state of the reaction. Since all the biochemical data were collected on minimal hammerheads that have a very different structure, the minimal hammerhead must be dynamic and occasionally adopt the quite different extended structure in order to cleave.

Minimal and extended hammerheads utilize a similar dynamic reaction mechanism for catalysis.

Analysis of the catalytic activity of identical mutations in the catalytic cores of nHH8, a very active "extended" hammerhead, and HH16, a less active "minimal" hammerhead, reveal that the tertiary Watson-Crick base pair between C3 and G8 seen in the recent structure of the Schistosoma mansoni extended hammerhead can be replaced by other base pairs in both backgrounds. This supports the model that both hammerheads utilize a similar catalytic mechanism but HH16 is slower because it infrequently samples the active conformation. The relative effect of different mutations at positions 3 and 8 also depends on the identity of residue 17 in both nHH8 and HH16. This synergistic effect can best be explained by transient pairing between residues 3 and 17 and 8 and 13, which stabilize an inactive conformation. Thus, mutants of nHH8 and possibly nHH8 itself are also in dynamic equilibrium with an inactive conformation that may resemble the X-ray structure of a minimal hammerhead. Therefore, both minimal and extended hammerhead structures must be considered to fully understand hammerhead catalysis.

When to believe what you see.

The recent X-ray crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni containing the rate-enhancing peripheral domain has a catalytic core that is very different from the catalytic core present in the structure of the "minimal" hammerhead, which lacks a peripheral domain (Martick and Scott, 2006). The new structure reconciles many of the disagreements between the minimal hammerhead structure and the biochemical data on the cleavage properties of chemically modified hammerheads. The new structure also emphasizes the dynamic nature of small RNA domains and provides a cautionary tale for everyone who tries to use structure to understand function.

Diet, activity, and overweight among preschool-age children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

INTRODUCTION: Overweight is affecting children at younger ages and in increasing numbers, putting them at risk for a lifetime of chronic disease. Consumption of unhealthy foods and time spent watching television have increased concurrently. METHODS: Parents of 526 children aged 2 to 4 years old enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) answered questions about their children's food and beverage consumption, television-viewing and computer time, and physical activity. The children's height and weight measurements were collected from administrative records. Crude and adjusted odds ratios were calculated to test for associations between demographic, consumption, and activity variables and overweight or at risk of overweight (body mass index > or =85th percentile for age and sex). RESULTS: Of the participants, 38% of the children were overweight or at risk of overweight. Hispanic and white children were twice as likely as black children to be overweight or at risk of overweight. Fifty-eight percent of the children drank more than one and 30% drank more than two 8-oz servings of fruit juice per day. The children who drank more than one serving of nonjuice fruit drink per day (30%) had increased odds of being overweight or at risk of overweight. On average, the children spent more than twice as much time watching television and using computers as they did engaging in physical activity. In multivariate analyses, race and ethnicity as well as physical activity were associated with being overweight or at risk of overweight. CONCLUSION: Efforts to improve nutrition and prevent overweight in children should focus on the parents of infants and toddlers and provide them with anticipatory guidance on physical activity for young children and nutrition and food transitions.

Hammerheads derived from sTRSV show enhanced cleavage and ligation rate constants.

The catalytic properties of the hammerhead ribozyme embedded in the (+) strand of the satellite tobacco ringspot viral genome are analyzed with the goal of obtaining the elemental rate constants of the cleavage (k(2)) and ligation (k(-)(2)) steps. Two different chimeras combining the sTRSV (+) hammerhead and the well-characterized hammerhead 16 were used to measure the cleavage rate constant (k(2)), the rate of approach to equilibrium (k(obs) = k(2) + k(-)(2)), and the fraction of full-length hammerhead at equilibrium (k(-)(2)/k(2) + k(-)(2)). When compared to minimal hammerheads that lack the recently discovered loop I-loop II interaction, an extended format hammerhead derived from sTRSV studied here shows at least a 20-fold faster k(2) and a 1300-fold faster k(-)(2) at 10 mM MgCl(2). However, the magnesium dependence of the cleavage rate is not significantly changed. Thus, the enhanced cleavage of this hammerhead observed in vivo is due to its higher intrinsic rate and not due to its tighter binding of magnesium ions. The faster k(-)(2) of this hammerhead suggests that ligation may be used to form circular RNA genomes. This in vitro system will be valuable for experiments directed at understanding the hammerhead mechanism and the role of the loop I-loop II interaction.

Childhood overweight in a New York City WIC population.

OBJECTIVES: We estimated the prevalence of overweight in a population of young children enrolled in a New York City Special Supplemental Nutrition Program for Women, Infants, and Children. METHODS: Administrative and survey data were collected from a sample of enrolled families. Body mass index (BMI) of 557 children aged 2, 3, and 4 years was compared by sociodemographic and nutrition characteristics. RESULTS: Forty percent of the children were overweight or at risk for overweight (BMI >/= 85th percentile). Compared with other racial/ethnic groups combined, Hispanic children were more than twice as likely (odds ratio = 2.6; 95% confidence interval = 1.8, 3.8) to be overweight or at risk for overweight. Two-year-olds were less likely to be overweight than 3- and 4-year-olds. CONCLUSIONS: Interventions to address childhood overweight should be culturally specific and target very young children.

Synthesis of sodium tantalate nanorods by alkalide reduction.

NaTaO3 nanorods were synthesized with high (>90%) yield by reduction of TaCl5 with THF solutions of the alkalide K+(15C5)2Na-, followed by product annealing under dynamic vacuum at 250 and 600 degrees C. In addition to the nanorods, the product is comprised of 5-10% approximately 10-nm diameter spheroidal NaTaO3 nanocrystals. The nanorods are generally longer than 500 nm, with some exceeding 1 mum, and 10-100 nm wide, with aspect ratios that vary between 10 and 20:1. Select area electron diffraction patterns of individual nanorods indicate that each nanorod is a single crystal with its axis oriented in the [010] direction.

Solution synthesis of gadolinium nanoparticles.

Gadolinium nanoparticles have been produced at subambient temperature by alkalide reduction. The nanoparticles display maxima in the temperature dependence of their magnetization, cooled in the absence of an applied external field, at T(max) of 5.0 and 17.5 K for unheated samples and samples annealed at 1000 degrees C for 4 h, respectively. Field cooled behavior deviates at temperatures slightly above T(max), increasing at lower temperature. Curie-Weiss law fits of the high-temperature data yield magnetic moments in close agreement with those expected for noninteracting Gd(3+) ions, suggesting that the behavior seen is due to a magnetic transition rather than superparamagnetism. Magnetization is linearly dependent on field at temperatures higher than 7-8 times T(max) and shows remanence-free hysteresis at lower temperature, suggesting metamagnetism. Some annealed samples show evidence of additional ferromagnetic interactions below approximately 170 K. Magnetic entropy curves generated from magnetization data are consistent with that expected for a paramagnet.