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In this cross-sectional population-based study, women had significantly higher crude incidence rates of both community-associated Clostridioides difficile infection (CA-CDI) and ambulatory antibiotic prescriptions compared to men in South Carolina in 2015. After adjustments for antibiotic prescription rates, there was no difference in the incidence rates of CA-CDI between the genders.
To examine the temporal trends in ambulatory antibiotic prescription fill rates and to determine the influences of age, gender, and location.
Population-based cohort study.
Ambulatory setting in South Carolina.
Patients ≤64 years of age from January 2012 to December 2017.
Aggregated pharmacy claims data for oral antibiotic prescriptions were utilized to estimate community antibiotic prescription rates. Poisson regression or Student t tests were used to examine overall temporal trend in antibiotic prescription rates, seasonal variation, and the trends across age group, gender, and rural versus urban location.
Overall antibiotic prescription rates decrease from 1,127 to 897 per 1,000 person years (P < .001). The decrease was more noticeable in persons aged <18 years (26%) and 18–39 years (20%) than in those aged 40–64 years (5%; P < .001 for all). Prescription rates were higher among females than males in all age groups, although this finding was the most pronounced in group aged 18–39 years (1,232 vs 585 per 1,000 person years; P < .0001). Annualized antibiotic prescription rates were higher during the winter months (December–March) than the rest of the year (1,145 vs 885 per 1,000 person years; P < .0001), and rates were higher in rural areas than in urban areas (1,032 vs 941 per 1,000 person years; P < .0001).
The decline in ambulatory antibiotic prescription rates is encouraging. Ongoing ambulatory antibiotic stewardship efforts across South Carolina should focus on older adults, rural areas, and during the winter season when antibiotic prescriptions peak.
Demographic monitoring is required in threatened species management, yet effective and efficient monitoring is challenging for species that are difficult to capture or susceptible to capture stress. One possible monitoring approach for such species is non-invasive genetic sampling with capture–recapture methods (genetic capture–recapture). We evaluated the performance of genetic capture–recapture in a challenging model system, monitoring the threatened Sonoran pronghorn Antilocapra americana sonoriensis. In an effort to determine the best (i.e. efficient, accurate, precise, cost-effective) method for abundance estimation, we used simulations to examine the optimal genetic capture–recapture faecal sampling design for this population. We simulated encounter histories for 100–300 individuals, with 0.33–3.33 samples/individual/session, in 1–3 sampling sessions. We explored trade-offs between sample size, number of sessions and multi-session (MARK) versus single-session (capwire) closed capture–recapture abundance estimators, and an accurate and precise estimate. We also compared the cost between the genetic capture–recapture approaches and current aerial monitoring methods. Abundance was biased positively in capwire and negatively in MARK. Bias increased and precision decreased with fewer samples/individual/session. Annual genetic capture–recapture monitoring cost was nearly twice the cost of aerial surveys, although genetic capture–recapture methods provided much higher precision. However at the current estimated abundance (c. 200), the same level of precision achieved with aerial methods can be obtained by collecting 0.75 samples/individual in a single session, for an annual cost saving of > USD 4,000. This approach of comparing estimator performance and cost can easily be applied to other systems and is a useful evaluation for managers to implement prior to designing capture–recapture studies.
Introduction: Hereditary angioedema (HAE) patients (both diagnosed and undiagnosed) commonly present to the emergency department (ED). Presenting symptoms (swelling and pain) may be erroneously attributed to common allergic and gastrointestinal conditions resulting in major delays in diagnosis and appropriate treatment. No published tools currently exist for HAE screening and management in undiagnosed disease. The overall goal of the study was to develop a HAE-RT tool for ED settings. Methods: A two-phase mixed methods approach was used to develop the HAE-RT Tool including: Phase 1: A Delphi Study [HAE specialists (N=9) and National Patient Advocacy Group Members (N=3)] was conducted to reach consensus (80% agreement) on predictor variables to include. Phase 2: A retrospective chart review was conducted to assess the predictive findings of the predictor variables. A convenient sample of patients presenting with angioedema (with and without HAE) between January 2012 January 2017 were included in the study. Results: Of the 12 experts invited, 9 (75%) participated in the Delphi study. Of 8 HAE-specific predictive variables, 4 reached consensuses including: (1) recurrent angioedema; (2) absence of urticaria; (3) past recurrent abdominal pain/swelling; (4) response to allergic therapy. The retrospective study included 85 patients (N=46 with HAE; N=39 non-HAE; overall 72% female). HAE patients were significantly more likely to have a family history of HAE (72% vs 0%; P<0.0001); previous recurrent angioedema (96%; P<0.009); present with no hives (91%; P<0.036); previous recurrent abdominal pain (80%; P<0.0001); and only 2% responded positively to allergy treatments (P<0.0001). Conclusion: Our study emphasizes the importance of key stakeholder involvement and feedback to facilitate the prioritization of important information that must be included in the design of an HAE-RT tool. The next step is to observe the effect of the HAE-RT tool on patient triage in the ED.
Many Neotropical felids are threatened with extinction due to direct effects of habitat destruction and/or human persecution. However, indirect and synergistic effects of human-felid conflict remain under-studied and potentially include increased stress and diet shifts that may negatively impact felid health. We hypothesized that faecal glucocorticoid metabolites (FGM) and endoparasite species richness (ESR) would be higher, and diet would shift, for felids outside protected areas where conflict occurs. In north-western Belize, a scat-detector dog located 336 faecal samples, identified to species and individual using DNA analyses. DNA amplification success was substantially higher within protected areas than outside. We detected jaguar, puma, ocelot, jaguarundi and domestic cat. FGMs were higher in puma and jaguarundi than in other felids, while ESR was similar across felids with domestic cats exhibiting the highest number of genera. Diet partitioning occurred among felids, but domestic cats may compete with ocelot and jaguarundi for small prey. Outside of protected areas, large cats shifted their diet to smaller prey and livestock remains were not found. Contrary to our hypotheses, FGM and ESR did not differ inside versus outside protected areas, but sample sizes were low in human-modified areas. We provide a baseline on wild felid adrenal activity, endoparasites and diet and suggest improvements to increase sample sizes outside protected areas. Our research provides a template for expanding non-invasive sampling approaches more widely across the range of Neotropical felids.
Household contacts of an index case of invasive meningococcal disease (IMD) are at increased risk of acquiring disease. In revising WHO guidance on IMD in sub-Saharan Africa, a systematic review was undertaken to assess the effect of chemoprophylaxis and of vaccination in preventing subsequent cases of IMD in household contacts following an index case. A literature search for systematic reviews identified a single suitable review on chemoprophylaxis in 2004 (three studies meta-analysed). A search for primary research papers published since 2004 on chemoprophylaxis and without a date limit on vaccination was therefore undertaken. There were 2381 studies identified of which two additional studies met the inclusion criteria. The summary risk ratio for chemoprophylaxis vs. no chemoprophylaxis (four studies) in the 30-day period after a case was 0·16 [95% confidence interval (CI) 0·04-0·64, P = 0·008]; the number needed to treat to prevent one subsequent case was 200 (95% CI 111-1000). A single quasi-randomized trial assessed the role of vaccination. The risk ratio for vaccination vs. no vaccination at 30 days was 0·11 (95% CI 0·01–2·07, P = 0·14). The results support the use of chemoprophylaxis to prevent subsequent cases of IMD in household contacts of a case. Conclusions about the use of vaccination could not be drawn.
The synthesis of organic and inorganic nano- and microspheres has attracted much interest for a variety of applications ranging from drug delivery to chemical storage and catalysis. We recently demonstrated the assembly of magnetic nanoparticles and polycations into hybrid microspheres in a single-step synthesis via complex coacervation. These microspheres showed viability for bio-applications as indicated by toxicity tests, and are therefore potential targeted drug delivery devices, as they can be directed magnetically. This work reports the recent progress on the potential use of these assemblies in drug release by controlling their porosity. Fluorescein tagged dextran molecules with different MW have been infiltrated into these entities to determine critical pore size by confocal fluorescence microscopy. Different physicochemical characterization results are also presented.
Non-invasive genetic sampling (NGS) is becoming a popular tool for population estimation. However, multiple NGS studies have demonstrated that polymerase chain reaction (PCR) genotyping errors can bias demographic estimates. These errors can be detected by comprehensive data filters such as the multiple-tubes approach, but this approach is expensive and time consuming as it requires three to eight PCR replicates per locus. Thus, researchers have attempted to correct PCR errors in NGS datasets using non-comprehensive error checking methods, but these approaches have not been evaluated for reliability. We simulated NGS studies with and without PCR error and ‘filtered’ datasets using non-comprehensive approaches derived from published studies and calculated mark–recapture estimates using CAPTURE. In the absence of data-filtering, simulated error resulted in serious inflations in CAPTURE estimates; some estimates exceeded N by[ges ]200%. When data filters were used, CAPTURE estimate reliability varied with per-locus error (Eμ). At Eμ=0.01, CAPTURE estimates from filtered data displayed <5% deviance from error-free estimates. When Eμ was 0.05 or 0.09, some CAPTURE estimates from filtered data displayed biases in excess of 10%. Biases were positive at high sampling intensities; negative biases were observed at low sampling intensities. We caution researchers against using non-comprehensive data filters in NGS studies, unless they can achieve baseline per-locus error rates below 0.05 and, ideally, near 0.01. However, we suggest that data filters can be combined with careful technique and thoughtful NGS study design to yield accurate demographic information.
The jaws of the marine worm Nereis sp. are made of protein fibers and are reinforced by zinc. Here we study a transverse section through the jaw using optical microscopy and nanoindentation. Optical microscopy images demonstrate a complex microstructure which includes channels that extend throughout the jaw. We suggest that these channels may be related to jaw remodeling. The mechanical results reveal spatial variations in both indentation hardness and reduced modulus. Specifically, the toothed side of the jaw (used for grasping food) is harder than the remainder of the jaw and the very exterior surface is hardest.
The purpose of the present study was to determine the long-term outcome of 76 children (40 females and 36 males) diagnosed and treated with modern antituberculosis drugs. The median age of the children on admission was 29.5 months and on follow-up 9 years. Antituberculosis therapy consisted of daily isoniazid (20mg/kg), rifampicin (20mg/kg), ethionamide (20mg/kg), and pyrazinamide (40mg/kg) for 6 months. Twenty-three children received daily prednisone (2–4mg/kg) for the first month of treatment. Raised intracranial pressure was actively monitored and treated. Patients with non-communicating hydrocephalus received ventriculo-peritoneal shunts shortly after admission while communicating hydrocephalus was treated with oral acetazolamide (100mg/kg/day) and furosemide (1mg/kg/day) in 3–4 divided doses. Communicating hydrocephalus that did not respond to this regimen within the first month of treatment also underwent ventriculo-peritoneal shunting. Only 20% of children were functionally completely normal at follow-up. Main areas of functional deficit were cognitive impairment (80%), poor scholastic progress (43%), and emotional disturbance (40%). Twenty-five per cent of children had evidence of motor impairment, but all could walk and only 5 of 76 children (6% of total) were unable to run. One child was blind but no child had sensori-neural deafness. It was concluded that these disabilities in children from mainly deprived socioeconomic backgrounds have serious implications for their future social, academic, and career prospects. A high index of suspicion of TBM in high tuberculosis incidence communities will help prevent the morbidity documented in this study.
This descriptive study investigated an outbreak of hepatitis A virus (HAV) infection among injecting drug users (IDUs) and their contacts. Twenty-seven cases of acute HAV infection were identified in a 5-month period. Connections with the local injecting drug using (IDU) population were established for 25 of the cases of whom 14 admitted to injecting drug use. HAV RNA genotyping revealed two HAV variants, closely related to variants found in Scandinavian IDUs and in South East Asia. The study demonstrates that once HAV enters the IDU population extensive outbreaks are possible. We recommend that all IDUs should be tested for HAV and hepatitis B virus (HBV) infections and offered combined hepatitis A and B vaccines if non-immune.
Jovian auroral emissions are observed at infrared, visible, ultraviolet, and x-ray wavelengths. As at Earth, pitch-angle scattering of energetic particles into the atmospheric loss cone and the acceleration of current-carrying electrons in field-aligned currents both play a role in exciting the auroral emissions. The x-ray aurora is believed to result principally from heavy ion precipitation, while the ultraviolet aurora is produced predominantly by precipitating energetic electrons. The magnetospheric processes responsible for the aurora are driven primarily by planetary rotation. Acceleration of Iogenic plasma by rotationally-induced electric fields results in both the formation of the energetic ions that are scattered and the formation of strong, field-aligned currents that communicate the torques from the ionosphere. In addition to rotation-driven processes, solar-wind-modulated processes in the outer magnetosphere may lead to highly, time-dependent acceleration and thus also contribute to jovian auroral activity. Observational evidence for both sources will be presented. See Waite et al. (2001, Nat., 410, 787).
Silicon germanium pMOSFETs with channel lengths down to 0.4m have been fabricated on limited area silicon germanium virtual substrates. The devices have a 5nm thick Si0.3Ge0.7 active layer grown by MBE on top of relaxed Si0.7Ge0.3 virtual substrate. Virtual substrates were grown on top of 10μm square silicon pillars defined by etching trenches around their perimeter into the original silicon substrate. This limits the area of the growth zone, which in turn promotes the relaxation of the virtual substrate. Electrical measurements on 2μm long channel devices show that the maximum mobility in the strained SiGe devices is 211cm2V-1cm-1, compared to 104cm2V-1cm-1 for silicon reference devices. This increase in hole mobility increases the current drive of 0.4m devices measured at Vgt=-2V, Vds=-2.5V from 154μA/m to 192μA/μm.
The development of the vitellaria of Fasciola hepatica within the liver of its rat host was studied by means of whole-mount stained preparations and transmission electron microscopy, together with light and electron immunocytochemistry using an antibody to vitelline protein B, an eggshell precursor protein synthesized by F. hepatica. No vitelline cells could be identified in flukes recovered from the liver parenchyma, by any of the methods used. In contrast, follicles were present in flukes at the earliest time of recovery from the bile duct, namely, 5 weeks 3 days post-infection. The vitellaria in these flukes formed a row of small follicles on either side of the body. Development of the follicles was rapid: by 6 weeks 3 days, the vitellaria resembled those in the adult fluke and eggs were present in the uterus. Immunolabelling was confined to the shell protein globules in the vitelline cells, confirming the packaging of the eggshell protein within the shell globule clusters.
Multi-photon excitation has been used in microscopy for nearly a decade, providing a number of demonstrated advantages over other methods for fluorescence imaging. Because excitation is achieved using longer, less energetic light, photodamage and photobleaching of the sample are reduced. Furthermore, since excitation occurs only at the focal point, this approach allows the practical collection of three-dimensionally resolved fluorescence images of live cells. However, due to the small two-photon cross-section of most fluorophores, pulsed lasers are required to generate detectable signal levels. This is due to the quadratic dependence of twophoton absorption on the instantaneous power of the laser. Typically, these lasers are pulsed at very high repetition frequencies, on the order of 106 pulses per second with pulse durations of a few hundreds of femtoseconds. For example, a titanium:sapphire (Ti:S) laser mode-locked at 76 Mhz can provide up to 100,000 watts of instantaneous power and is ideal for exciting two-photon events.
Pangea Resources International AG, Switzerland, has put forward the concept of an international geological repository in an Australian desert area, for final disposal of certain of the world's high-level radioactive wastes and surplus fissile materials. Already publicly contentious in Australia, the concept raises unusual issues in safety and environmental assessment. It is timely, therefore, to consider why and how an initial case for such a repository might be made, in comparison with national options for high-level waste disposal that it might displace.
There are several stages ahead of development of a formal safety case for an international repository. The first, and almost certainly the most challenging, is winning of public and political acceptance in the host country that such a repository is the ‘best’ solution to a global problem.
We consider the basic need to identify and encompass the concerns of widely disparate stakeholders — industry, governments, national and international regulators, environmental interest groups and the public at large — so that public and political debates can be informed effectively. Many key issues will require comparison both of risks arising from very different operations, and of dissimilar prospective safety performances of complete disposal systems over periods spanning thousands of generations. Nevertheless, we conclude that the validity of such a comparative assessment could be assured by consistent application of a judicious blend of assessment techniques across the alternatives. We also conclude that its usefulness as a vehicle for public discussion would be enhanced by careful attention to public concerns, and by transparently independent review by scientific, technical, sociological and ethical specialists.
A new approach to materials design is presented, utilizing specific recognition and assembly at the molecular level. The approach described exploits the control over polymer chain microstructure afforded by biosynthesis to produce proteinbased materials with precisely defined physical properties. Incorporated into these materials are recognition elements that stringently control the placement and organization of each chain within higher order superstructures. The proteins, designated Recognin A2 through Recognin E2, are recombinant polypeptides designed de novo from both natural consensus sequences and an appreciation of the physical principles governing biological recognition. These materials are designed to examine the forces involved in specific recognition and complexation. through control of charge identity and placement, a pattern for specific interaction can be introduced. A subset of these materials are programmed to spontaneously assemble into complex, multicomponent structures and represent the first step in a rational approach to nanometer-scale structural design.