The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.
Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.


A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library.
We describe the construction of a DNA-encoded chemical library comprising 148 135 members, generated through the self-assembly of two sub-libraries, containing 265 and 559 members, respectively. The library was designed to contain building blocks potentially capable of forming covalent interactions with target proteins. Selections performed with JNK1, a kinase containing a conserved cysteine residue close to the ATP binding site, revealed the preferential enrichment of a 2-phenoxynicotinic acid moiety (building block A82) and a 4-(3,4-difluorophenyl)-4-oxobut-2-enoic acid moiety (building block B272). When the two compounds were joined by a short PEG linker, the resulting bidentate binder (A82-L-B272) was able to covalently modify JNK1 in the presence of a large molar excess of glutathione (0.5 mm), used to simulate intracellular reducing conditions. By contrast, derivatives of the individual building blocks were not able to covalently modify JNK1 in the same experimental conditions. The A82-L-B272 ligand was selective over related kinases (BTK and GAK), which also contain targetable cysteine residues in the vicinity of the active site.


A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units.
To study late onset systemic infections with coagulase negative staphylococci. Prospective longitudinal study of coagulase negative staphylococcal infection in 18 Australasian neonatal nurseries. From 1991 to 2000 inclusive, there were 1281 cases of coagulase negative staphylococcal (CoNS) sepsis, comprising 57.1% of all late onset infections. The male/female ratio was 1.27:1 (p < 0.05). The incidence of CoNS sepsis was 3.46 episodes per 1000 live births. Most infected babies (71%) were 24-29 weeks gestation at birth (mode 26 weeks). The first positive culture was day 7-14 in 49% of babies (mode 10 days). Five cases of meningitis were reported, an incidence of 0.4% of all CoNS infections. Twenty nine babies (2.3%) had concurrent necrotising enterocolitis and CoNS septicaemia. Four babies (0.3%) died from CoNS infection, but CoNS infection possibly contributed to the death of an additional 20 babies (1.6%). The mortality directly attributable to CoNS infection was significantly lower than that from late onset infections with Staphylococcus aureus (13.1%; relative risk (RR) = 36.1 (95% confidence interval (CI) 13.0 to 100.2) or with Gram negative bacilli (14.2%; RR = 45.5 (95% CI 16.8 to 123.3)). CoNS are currently responsible for most late onset neonatal infections. Most infected babies are < 30 weeks gestation at birth, and usually present between 7 and 14 days of age. CoNS infections may be associated with necrotising enterocolitis, although causality is unproven. Neonatal CoNS infections are relatively benign: meningitis is rare and mortality low compared with infection from other organisms. Over-vigorous attempts to reduce the incidence of CoNS infections using prophylactic antibiotics are not advisable.


The Uganda Newborn Study (UNEST): an effectiveness study on improving newborn health and survival in rural Uganda through a community-based intervention linked to health facilities - study protocol for a cluster randomized controlled trial.
Reducing neonatal-related deaths is one of the major bottlenecks to achieving Millennium Development Goal 4. Studies in Asia and South America have shown that neonatal mortality can be reduced through community-based interventions, but these have not been adapted to scalable intervention packages for sub-Saharan Africa where the culture, health system and policy environment is different. In Uganda, health outcomes are poor for both mothers and newborn babies. Policy opportunities for neonatal health include the new national Health Sector Strategic Plan, which now prioritizes newborn health including use of a community model through Village Health Teams (VHT). The aim of the present study is to adapt, develop and cost an integrated maternal-newborn care package that links community and facility care, and to evaluate its effect on maternal and neonatal practices in order to inform policy and scale-up in Uganda. Through formative research around evidence-based practices, and dialogue with policy and technical advisers, we constructed a home-based neonatal care package implemented by the responsible VHT member, effectively a Community Health Worker (CHW). This CHW was trained to identify pregnant women and make five home visits - two before and three just after birth - so that linkages will be made to facility care and targeted messages for home-care and care-seeking delivered. The project is improving care in health units to provide standardized care for the mother and the newborn in both intervention and comparison areas.The study is taking place in a new Demographic Surveillance Site in two rural districts, Iganga and Mayuge, in Uganda. It is a two-arm cluster randomized controlled design with 31 intervention and 32 control areas (villages). The comparison parishes receive the standard care already being provided by the district, but to the intervention villages are added a system for CHWs to visit the mother five times in her home during pregnancy and the neonatal period. Both areas benefit from a standardized strengthening of facility care for mothers and neonates. UNEST is designed to directly feed into the operationalization of maternal and newborn care in the national VHT strategy, thereby helping to inform scale-up in rural Uganda. The study is registered as a randomized controlled trial, number ISRCTN50321130.


Sheep breed and shearing influences attraction and blood-feeding behaviour of Culicoides (Diptera: Ceratopogonidae) on a UK farm.
Culicoides biting midges (Diptera: Ceratopogonidae) are responsible for the biological transmission of arboviruses of international importance between ruminant livestock. These arboviruses include bluetongue virus (BTV) and Schmallenberg virus (SBV), which have emerged in unprecedented outbreaks in northern Europe. The impact of breed and shearing of sheep on Culicoides: host contact rates has not been investigated in detail and has the potential to influence arbovirus transmission and control measures employed to limit spread. Attraction of Culicoides to Hartline and Hartline/Suffolk cross-breed sheep was compared using 224 drop trap collections over 22 nights and 181 catches from sheared or unsheared Hartline/Suffolk ewes were made over 17 nights to compare Culicoides activity and rates of blood engorgement. A total of 31,314 Culicoides was collected in the two trials and females of the subgenus Avaritia represented over 96.9% of individuals collected. Attraction to breed was dependent upon species of Culicoides and physiological status, with a significantly greater number of individuals collected on the cross-breed sheep. Shearing of sheep did not significantly increase or decrease the number of Culicoides attracted but increased the rate of successful engorgement. Both breed and shearing were shown to influence Culicoides biting rate on sheep. These data are useful in a direct context in understanding the likely impact of control measures against arboviruses including BTV and SBV and additionally in providing data from field-based studies to enable modelling exercises of arbovirus transmission and spread.


Geographic access to dental care varies in Missouri and Wisconsin.
To examine geographic access to dental providers for the general population and children with public insurance in Missouri and Wisconsin. Using a newly constructed dentist office database from the American Dental Association master file and other sources, we use the two-step floating area catchment area method to calculate population to provider ratios at the census block group level. These ratios are used to determine potential geographic dentist shortage areas. We utilize street network data to estimate travel times and catchment areas between population centers and dental offices. This methodology accounts for the actual spatial distribution of dental providers and potential dental patients. Within and across Missouri and Wisconsin, there is some variation in geographic access to dental offices for the general population and publicly insured children. More than 90 percent of publicly insured children have access to dental providers within 30 minutes. Among the states examined, Missouri has more geographic disparities to dental care. The Health Resources and Services Administration, which designates dental health professional shortage areas, relies on administrative boundaries to calculate population to dental provider ratios. These boundaries may not reflect actual or "real-time" dental care markets. The methods employed in this paper may give policymakers a template to better determine geographic dentist shortage areas.


An Artificial Intelligence Approach for Gears Diagnostics in AUVs.
In this paper, an intelligent scheme for detecting incipient defects in spur gears is presented. In fact, the study has been undertaken to determine these defects in a single propeller system of a small-sized unmanned helicopter. It is important to remark that although the study focused on this particular system, the obtained results could be extended to other systems known as AUVs (Autonomous Unmanned Vehicles), where the usage of polymer gears in the vehicle transmission is frequent. Few studies have been carried out on these kinds of gears. In this paper, an experimental platform has been adapted for the study and several samples have been prepared. Moreover, several vibration signals have been measured and their time-frequency characteristics have been taken as inputs to the diagnostic system. In fact, a diagnostic system based on an artificial intelligence strategy has been devised. Furthermore, techniques based on several paradigms of the Artificial Intelligence (Neural Networks, Fuzzy systems and Genetic Algorithms) have been applied altogether in order to design an efficient fault diagnostic system. A hybrid Genetic Neuro-Fuzzy system has been developed, where it is possible, at the final stage of the learning process, to express the fault diagnostic system as a set of fuzzy rules. Several trials have been carried out and satisfactory results have been achieved.


Hemodynamic changes in chick embryos precede heart defects after cardiac neural crest ablation.
Neural crest cells are known to contribute to the normal architecture of the heart and aortic arch arteries. Ablation of neural crest cells over somites 1 to 3 in the chick embryo prevents conotruncal septation and results in persistent truncus arteriosus. To determine whether a deficiency of cardiac neural crest cells produces hemodynamic changes prior to the development of identifiable structural defects in the heart, we measured dorsal aortic blood velocity and vitelline artery blood pressure in lesioned and control embryos at a period of cardiac morphogenesis prior to septal formation. The internal diameter of the dorsal aorta at the level of the sinus venosus and the internal diameter of the aortic arch arteries at their midpoints were measured in embryos at Stage 18 of development using a filar micrometer eyepiece and a dissecting microscope. Embryos with neural crest lesions had significantly greater dorsal aortic blood flow velocity than control embryos. In addition, embryos lacking cardiac neural crest had significantly lower systolic and diastolic blood pressures than control embryos. There was no difference in heart rate, dorsal aortic diameter or internal diameter of the aortic arch arteries between lesioned and control embryos. Scanning electron micrographs revealed no gross morphological differences in cardiac looping or conotruncal wall development between lesioned and control embryos; however, embryos with cardiac neural crest ablations developed markedly hypoplastic 4th pharyngeal arches. This data suggests that hemodynamic changes precede the onset of structural heart defects in embryos with cardiac neural crest ablations.


2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.


The prevalence and clinical significance of inhalant withdrawal symptoms among a national sample.
BACKGROUND: Inhalants are among the most common and dangerous forms of substance use, but very little research on inhalant use disorders exist. Unlike other substances, the Diagnostic and Statistical Manual, 4th edition (DSM-IV) indicates that inhalants do not have an associated withdrawal syndrome among persons who meet criteria for inhalant dependence. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions, this study examines the prevalence of withdrawal symptoms among inhalant users. Prevalence of inhalant withdrawal symptoms for inhalants was also compared with the prevalence of cocaine withdrawal symptoms to help determine the presence of an inhalant withdrawal syndrome. RESULTS: Approximately 47.8% of persons who met criteria for inhalant dependence reported experiencing three or more inhalant-related withdrawal symptoms that were clinically significant. Among those with inhalant dependence, almost half of the withdrawal symptoms were as common as the corresponding withdrawal symptoms experienced by persons with cocaine dependence. Furthermore, the percentage of persons with inhalant dependence reporting clinically significant inhalant withdrawal symptoms was almost equal to the percentage of persons with cocaine dependence reporting clinically significant cocaine withdrawal symptoms. CONCLUSIONS: These data provide evidence for an inhalant-related withdrawal syndrome among persons with inhalant dependence. Revisions to DSM-IV should consider including inhalant withdrawal as a diagnostic criterion for this disorder.


Preventing the transmission of mitochondrial DNA disorders using prenatal or preimplantation genetic diagnosis.
Mitochondrial disorders are among the most common inborn errors of metabolism; at least 15% are caused by mitochondrial DNA (mtDNA) mutations, which occur de novo or are maternally inherited. For familial heteroplasmic mtDNA mutations, the mitochondrial bottleneck defines the mtDNA mutation load in offspring, with an often high or unpredictable recurrence risk. Oocyte donation is a safe option to prevent the transmission of mtDNA disease, but the offspring resulting from oocyte donation are genetically related only to the father. Prenatal diagnosis (PND) is technically possible but usually not applicable because of limitations in predicting the phenotype. For de novo mtDNA point mutations, recurrence risks are low and PND can be offered to provide reassurance regarding fetal health. PND is also the best option for female carriers with low-level mutations demonstrating skewing to 0% or 100%. A fairly new option for preventing the transmission of mtDNA diseases is preimplantation genetic diagnosis (PGD), in which embryos with a mutant load below a mutation-specific or general expression threshold of 18% can be transferred. PGD is currently the best reproductive option for familial heteroplasmic mtDNA point mutations. Nuclear genome transfer and genome editing techniques are currently being investigated and might offer additional reproductive options for specific mtDNA disease cases.


Novel multitargeted anticancer oral therapies: sunitinib and sorafenib as a paradigm.
The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases--such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas--considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is tyically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities mandate prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.


The initiation of the heart beat.
During a normal lifetime, the heart may beat over 2 billion times, but the mechanisms by which the heart beats are initiated remain a subject of intense investigation. Since the discovery of a pacemaker current (I(f)) in 1978, multiple studies have shown that rhythmic changes in membrane voltage (the "membrane voltage clock") underlie the mechanisms of automaticity. The I(f) is a depolarization current activated during hyperpolarization. Therefore, when the cardiac cells recover, the I(f) is activated and slowly depolarizes the cell membrane, leading to the onset of action potential. Recent studies, however, suggest that increased intracellular Ca (Ca(i)) induced by spontaneous rhythmic sarcoplasmic reticulum Ca release (the "calcium clock") is also jointly responsible for the initiation of the heart beat. Elevated Ca(i) activates another ionic current (the sodium-calcium exchanger current or I(NCX)), leading to spontaneous phase 4 depolarization. Under normal conditions, both clocks are needed to initiate the heart beat. Malfunction of the clocks is associated with sinus node dysfunction in heart failure and atrial fibrillation. More studies are needed to determine how both clocks work together to initiate heart beat under normal and disease conditions.


The host cell response in the local graft-versus-host reaction induced in the kidneys of F 1 rats by parental thoracic duct lymphocytes.
Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F(1) rats labeled with tritiated thymidine (TdR(3)H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR(3)H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body gamma-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F(1) bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F(1) type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls. Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F(1)-type TDL in the apparent absence of mononuclear phagocytes. The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.


Specific brain regions of female rats are differentially depleted of docosahexaenoic acid by reproductive activity and an (n-3) fatty acid-deficient diet.
Low tissue levels of (n-3) PUFA, particularly docosahexaenoic acid [DHA, 22:6(n-3)], are implicated in postpartum depression. Brain DHA content is depleted in female rats undergoing pregnancy and lactation when the diet supplies inadequate (n-3) PUFA. In this study, the effects of DHA depletion as a result of reproductive activity and an (n-3) PUFA-deficient diet were examined in 8 specific brain regions of female rats after undergoing 2 sequential reproductive cycles. Virgin females, fed the alpha-linolenic acid (ALA)-containing or deficient (low-ALA) diets for a commensurate duration (13 wk) served as a control for reproduction. Total phospholipid composition of each brain region was determined at weaning (postnatal d 21) by TLC/GC. The regional PUFA composition of ALA virgins was similar to that previously measured in male rats. All brain regions examined were affected by reproductive activity and/or the low-ALA diet; however, the magnitude of the loss of DHA and compensatory incorporation of docosapentaenoic acid [(n-6) DPA, 22:5(n-6)] varied among brain regions. In low-ALA parous dams, frontal cortex (77% of ALA virgin) and temporal lobe (83% of ALA virgin), regions involved in cognition and affect, were among those exhibiting the greatest depletion of DHA. Caudate-putamen also exhibited significant depletion of DHA (82% of ALA virgin), whereas only (n-6) DPA levels were altered in ventral striatum, hypothalamus, hippocampus, and cerebellum. This pattern of changes in regional DHA and (n-6) DPA content suggests that specific neuronal systems may be differentially affected by depletion of brain DHA in the postpartum organism.


ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins.
Ca(2+)-activated Cl(-) channels (CaCCs) participate in numerous physiological functions such as neuronal excitability, sensory transduction, and transepithelial fluid transport. Recently, it was shown that heterologously expressed anoctamins ANO1 and ANO2 generate currents that resemble native CaCCs. The anoctamin family (also called Tmem16) consists of 10 members, but it is not known whether all members of the family are CaCCs. Expression of ANOs 3-7 in HEK293 cells did not generate Cl(-) currents activated by intracellular Ca(2+), as determined by whole cell patch clamp electrophysiology. With the use of confocal imaging, only ANO1 and ANO2 traffic to the plasma membrane when expressed heterologously. Furthermore, endogenously expressed ANO7 in the human prostate is predominantly intracellular. We took a chimeric approach to identify regions critical for channel trafficking and function. However, none of the chimeras of ANO1 and ANO5/7 that we made trafficked to the plasma membrane. Our results suggest that intracellular anoctamins may be endoplasmic reticulum proteins, although it remains unknown whether these family members are CaCCs. Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease.


Short-chain fatty acids and ceca microbiota profiles in broilers and turkeys in response to diets supplemented with phytase at varying concentrations, with or without xylanase.
Two independent studies were performed, each with a 3 × 2 factorial arrangement to compare the response in broilers and turkeys to phytase and xylanase supplementation on cecal fermentation and microbial populations. For both studies, 960 Ross 308 and 960 BUT 10 (1-day-old) were allocated to 1 of 6 experimental treatments: (1) control diet, containing the standard dose (100 g/ton) of phytase (STD-Xyl); (2) the control diet with 100 g/ton of xylanase (STD + Xyl); (3) the control diet supplemented on top with 2 fold the standard dose of phytase (200 g/ton), also referred as superdosing (SD-Xyl); (4) the superdosed diet with 100 g/ton of xylanase (SD + Xyl); (5) the control diet supplemented with 5-fold the standard dose of phytase (500 g/ton), also referred as megadosing (MD-Xyl); and (6) the megadosed diet with 100 g/ton of xylanase (MD + Xyl). Each treatment had 8 replicates of 20 animals. Broiler and turkey diets, based on wheat, soybean meal, rapeseed, and barley, and water were available ad libitum. On day 28, the cecal contents from 5 birds per pen were collected. The profile of short-chain fatty acids (SCFA) and microbiome structure (by % guanidine and cytosine [G + C] method) were analyzed. Selected % G + C fractions were used for 16S rDNA sequencing for the identification of bacteria. No treatment effects were noted on SCFA concentrations in either broilers or turkeys. Broilers fed MD diets had greater proportions of unclassified Clostridiales, Mollicutes (RF9) and Faecalibacterium. Xylanase supplementation in broilers resulted in lower proportions of Lactobacillus but increased Mollicutes (RF9), unclassified Ruminococcus, unclassified Clostridiales, and Bifidobacterium. The microbiome in turkeys was unaffected by phytase supplementation, but xylanase supplementation increased the proportions of Lachnospiraceae (Incertae sedis), Lactobacillus, and Bifidobacterium. Supplementation of turkey diets with increasing doses of phytase did not affect the cecal microbiota in contrast to what was observed in broilers. In contrast, xylanase supplementation in both species led to significant changes in the microbial populations, suggesting a positive influence through the provision of oligosaccharides.


Pediatric emergency mass critical care: the role of community preparedness in conserving critical care resources.
Public health emergencies require resources at state, regional, federal, and often international levels; however, community preparedness is the crucial first step in managing these events and mitigating their consequences, particularly for children. Community preparedness can be optimized through system-wide planning that includes integrating multiple points of contact, such as the community, prehospital care, health facilities, and regional level of care assets.Citizen readiness, call centers, alternate care facilities, emergency medical services, and health emergency operations centers linked to community incident command systems should be considered as important options for delivery of population-based care. Early collaboration between pediatric clinicians and public health authorities is essential to ensure that pediatric needs are addressed in community preparedness for mass critical care events. In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. The Pediatric Emergency Mass Critical Care Task Force recommends active promotion of programs to ensure an informed citizenry; education of children and families in Centers for Disease Control and Prevention community mitigation strategies; emphasis on community-level preparedness empowering the public to provide self care; use of 9-1-1 telephone triage with pre-established protocols and in coordination with emergency medical services; and advocacy for healthcare coalitions and other creative operational concepts that provide guidance and protocols for care of the pediatric population.


Melanoma - role of the environment and genetics.
Melanoma rates have increased in populations that are mainly European. The main etiologic factor is ultraviolet radiation, from the sun as well as artificial tanning devices. Host factors such as skin color, number of nevi, hair and eye color and tanning ability are critical factors in modifying an individual's response to the sun. Genetic factors interact with host factors and environmental factors to increase risk. This review summarizes our current knowledge of environment and genetics on melanoma risk and on gene-environment interaction.


Evaluating the Performance of Malaria Genetics for Inferring Changes in Transmission Intensity Using Transmission Modeling.
Substantial progress has been made globally to control malaria, however there is a growing need for innovative new tools to ensure continued progress. One approach is to harness genetic sequencing and accompanying methodological approaches as have been used in the control of other infectious diseases. However, to utilize these methodologies for malaria, we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment, which all impact the level of genetic diversity and relatedness of malaria parasites. We develop an individual-based transmission model to simulate malaria parasite genetics parameterized using estimated relationships between complexity of infection and age from five regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterize the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The model predicted malaria prevalence with a mean absolute error of 0.055. Different assumptions about the availability of sample metadata were considered, with the most accurate predictions of malaria prevalence made when the clinical status and age of sampled individuals is known. Parasite genetics may provide a novel surveillance tool for estimating the prevalence of malaria in areas in which prevalence surveys are not feasible. However, the findings presented here reinforce the need for patient metadata to be recorded and made available within all future attempts to use parasite genetics for surveillance.


The mechanism of catalysis and the inhibition of the Bacillus cereus zinc-dependent beta-lactamase.
The plot of kcat/Km against pH for the Bacillus cereus 569/H beta-lactamase class B catalysed hydrolysis of benzylpenicillin and cephalosporin indicates that there are three catalytically important groups, two of pKa 5.6+/-0.2 and one of pKa 9.5+/-0.2. Below pH 5 there is an inverse second-order dependence of reactivity upon hydrogen ion concentration, indicative of the requirement of two basic residues for catalysis. These are assigned to zinc(II)-bound water and Asp-90, both with a pKa of 5.6+/-0.2. A thiol, N-(2'-mercaptoethyl)-2-phenylacetamide, is an inhibitor of the class B enzyme with a Ki of 70 microM. The pH-dependence of Ki shows similar pH inflections to those observed in the catalysed hydrolysis of substrates. The pH-independence of Ki between pH 6 and 9 indicates that the pKa of zinc(II)-bound water must be 5.6 and not the higher pKa of 9.5. The kinetic solvent isotope effect on kcat/Km is 1.3+/-0.5 and that on kcat is 1.5. There is no effect on reactivity by either added zinc(II) or methanol. The possible mechanisms of action for the class B beta-lactamase are discussed, and it is concluded that zinc(II) acts as a Lewis acid to stabilize the dianionic form of the tetrahedral intermediate and to provide a hydroxide-ion bound nucleophile, whereas the carboxylate anion of Asp-90 acts as a general base to form the dianion and also, presumably, as a general acid catalyst facilitating C-N bond fission.


African Americans' opinions about human-genetics research.
Research on attitudes toward genetics and medicine registers skepticism among minority communities, but the reasons for this skepticism are not well known. In the past, studies linked mistrust of the medical system to historical ethics violations involving minority groups and to suspicions about ideological premise and political intent. To assess public knowledge, attitudes, and behavior regarding human-genetics research, we surveyed 858 Americans onsite in four community settings or online in a geographically nonspecific manner. Compared to participants as a whole, African Americans were significantly more likely to believe that clinical trials might be dangerous and that the federal government knowingly conducted unethical research, including studies in which risky vaccines were administered to prison populations. However, African Americans were also significantly more likely to believe that the federal government worked to prevent environmental exposure to toxicants harmful to people with genetic vulnerabilities. Our data suggest that most Americans trust government to act ethically in sponsoring and conducting research, including genetics research, but that African Americans are particularly likely to see government as powerfully protective in some settings yet selectively disingenuous in others.


Intra-scaffold continuous medium flow combines chondrocyte seeding and culture systems for tissue engineered trachea construction.
In this study we tested the possibility of seeding chondrocytes into poly (ethylene glycol)-terephthalate-poly (butylene terephthalate) PEOT/PBT scaffold through an intra-scaffold medium flow and the impact of this continuous medium flow on subsequent chondrocyte-scaffold culture. Eight cubic PEOT/PBT co-polymers (1 cm(3)) were assigned into two groups. In the semi-dynamic seeding group a continuous medium flow was created inside the scaffolds by a pump system. Around six million chondrocytes were harvested each day, suspended in 1 ml medium and delivered onto the scaffold through the perfusion for a sequential five days. Traditional chondrocytes directly seeding and static culture method was performed as control. Scanning electron microscopy (SEM) and histology assessments were performed to evaluate the distribution of chondrocytes inside the scaffolds and MTT test was chosen to check cell vitality. SEM pictures and histology slices from the perfusion group showed a better three-dimensional cell growth and extensive cell distribution inside the scaffolds; while in the control group chondrocytes only dispersedly formed a monolayer on the surface of scaffolds. Accordingly, MTT results from the perfusion group were much higher than those from control group (0.123 vs. 0.067, P<0.01). Continuous medium perfusion inside PEOT/PBT scaffold effectively combines chondrocyte seeding and culture systems for the reconstruction of tissue engineered trachea.


Complete ultrafast charge carrier dynamics in photo-excited all-inorganic perovskite nanocrystals (CsPbX3).
Understanding the nature and dynamics of the photo-induced transients of all-inorganic perovskite nanocrystals (NCs) is key to their exploitation in potential applications. In order to determine the nature of charge carriers, their deactivation pathways and dynamics, the photo-induced transients of CsPbBr3, CsPbBr2I, CsPbBr1.5I1.5 and CsPbI3 NCs are spectrally and temporally characterized employing a combination of femtosecond transient absorption (TA) and photoluminescence (PL) up-conversion techniques and global analysis of the data. The results provide distinct identities of the excitons and free charge carriers and distinguish the hot charge carriers from the cold ones. The carrier trapping is attributed to the electrons and their dynamics is unaffected in mixed halide perovskites. The excitation energy dependence of the TA dynamics suggests that the trap states are shallow in nature and mainly limited near the band-edge level. In mixed halide perovskites, an increase in the iodine content leads to hole trapping in a short time scale (<5 ps). The insights obtained from this study are likely to be helpful for tuning the photo-response of these substances and their better utilization in light-based applications.


A Bayesian Approach to Inferring Rates of Selfing and Locus-Specific Mutation.
We present a Bayesian method for characterizing the mating system of populations reproducing through a mixture of self-fertilization and random outcrossing. Our method uses patterns of genetic variation across the genome as a basis for inference about reproduction under pure hermaphroditism, gynodioecy, and a model developed to describe the self-fertilizing killifish Kryptolebias marmoratus. We extend the standard coalescence model to accommodate these mating systems, accounting explicitly for multilocus identity disequilibrium, inbreeding depression, and variation in fertility among mating types. We incorporate the Ewens sampling formula (ESF) under the infinite-alleles model of mutation to obtain a novel expression for the likelihood of mating system parameters. Our Markov chain Monte Carlo (MCMC) algorithm assigns locus-specific mutation rates, drawn from a common mutation rate distribution that is itself estimated from the data using a Dirichlet process prior model. Our sampler is designed to accommodate additional information, including observations pertaining to the sex ratio, the intensity of inbreeding depression, and other aspects of reproduction. It can provide joint posterior distributions for the population-wide proportion of uniparental individuals, locus-specific mutation rates, and the number of generations since the most recent outcrossing event for each sampled individual. Further, estimation of all basic parameters of a given model permits estimation of functions of those parameters, including the proportion of the gene pool contributed by each sex and relative effective numbers.


Procalcitonin, a donor-specific predictor of early graft failure-related mortality after heart transplantation.
To date, donor-specific markers to predict outcome after heart transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been found in infectious inflammation with systemic reactions and/or poor organ perfusion but have not been studied in heart donors. We evaluated PCT as a predictor of early graft failure-related mortality after HTx. PCT and C-reactive protein (CRP) serum concentrations were measured in samples collected immediately before pericardium opening from 81 consecutive brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2) were excluded from analysis. The remaining donors were retrospectively divided into 2 groups: donors for recipients who died within 30 days after HTx, after an early graft failure (group II, n=8), and all other donors (group I, n=71). No differences in donor and recipient demographic characteristics were found between groups. Areas under the receiver operating characteristic curves for graft failure-related mortality were 0.71 for PCT and 0.64 for CRP. A PCT value >2 ng/mL as a predictor of graft failure-related mortality had a specificity of 95.8% and sensitivity of 50.0%. The odds ratio for graft failure-related mortality for recipients of hearts from donors with PCT levels >2 ng/mL was 22.7 (unadjusted, 95% CI 3.7 to 137.8, P=0.0007) and 43.8 (after adjustment for prespecified potential confounders, 95% CI 1.4 to 1361.0, P=0.031). A PCT level >2 ng/mL in a cardiac donor at the time of explantation appears to predict early graft failure-related mortality.


A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes.
Rhinoscleroma is a human specific chronic disease characterized by the formation of granuloma in the airways, caused by the bacterium Klebsiella pneumoniae subspecies rhinoscleromatis, a species very closely related to K. pneumoniae subspecies pneumoniae. It is characterized by the appearance of specific foamy macrophages called Mikulicz cells. However, very little is known about the pathophysiological processes underlying rhinoscleroma. Herein, we characterized a murine model recapitulating the formation of Mikulicz cells in lungs and identified them as atypical inflammatory monocytes specifically recruited from the bone marrow upon K. rhinoscleromatis infection in a CCR2-independent manner. While K. pneumoniae and K. rhinoscleromatis infections induced a classical inflammatory reaction, K. rhinoscleromatis infection was characterized by a strong production of IL-10 concomitant to the appearance of Mikulicz cells. Strikingly, in the absence of IL-10, very few Mikulicz cells were observed, confirming a crucial role of IL-10 in the establishment of a proper environment leading to the maturation of these atypical monocytes. This is the first characterization of the environment leading to Mikulicz cells maturation and their identification as inflammatory monocytes.


Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity.
PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases. The protein is organized into two domains separated by a groove lined by highly conserved residues. To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate. In the complex, the peptide binds at the interface of a peptide-induced dimer interface. Conserved residues of the interdomain groove contribute to the peptide binding site and dimer interface. Structure-guided mutational studies showed that in vivo PTPA activity is influenced by mutations on the surface of the peptide binding pocket, the same mutations that also influenced the in vitro activation of PP2Ai and PPIase activity.


Stakeholder perspectives on new ways of delivering unscheduled health care: the role of ownership and organizational identity.
To explore stakeholder perspectives of the implementation of a new, national integrated nurse-led telephone advice and consultation service [National Health Service 24 (NHS 24)], comparing the views of stakeholders from different health care organizations. Semi-structured interviews with 26 stakeholders including partner organizations located in primary and secondary unscheduled care settings [general practitioner (GP) out-of-hours cooperative; accident and emergency department; national ambulance service, members of NHS 24 and national policy makers. Attendance at key meetings, documentary review and email implementation diaries provided a contextual history of events with which interview data could be compared. The contextual history of events highlighted a fast-paced implementation process, with little time for reflection. Key areas of partner concern were increasing workload, the clinical safety of nurse triage and the lack of communication across the organizations. Concerns were most apparent within the GP out-of-hours cooperative, leading to calls for the dissolution of the partnership. Accident and emergency and ambulance service responses were more conciliatory, suggesting that such problems were to be expected within the developmental phase of a new organization. Further exploration of these responses highlighted the sense of ownership within the GP cooperative, with GPs having both financial and philosophical ownership of the cooperative. This was not apparent within the other two partner organizations, in particular the ambulance service, which operated on a regional model very similar to that of NHS 24. As the delivery of unscheduled primary health care crosses professional boundaries and locations, different organizations and professional groups must develop new ways of partnership working, developing trust and confidence in each other. The results of this study highlight, for the first time, the key importance of understanding the professional ownership and identity of individual organizations, in order to facilitate the most effective mechanisms to enable that partnership working.


Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity.
Obesity in humans and in rodents is usually associated with high circulating leptin levels and leptin resistance. To examine the molecular basis for leptin resistance, we determined the ability of leptin to induce hypothalamic STAT3 (signal transducer and activator of transcription) signaling in C57BL/6J mice fed either low-fat or high-fat diets. In mice fed the low-fat diet, leptin activated STAT3 signaling when administered via the intraperitoneal (ip) or the intracerebroventricular (icv) route, with the half-maximal dose being 30-fold less when given by the icv route. The high-fat diet increased body-weight gain and plasma leptin levels. After 4 weeks on the diet, hypothalamic STAT3 signaling after ip leptin administration was equivalent in both diet groups. In contrast, peripherally administered leptin was completely unable to activate hypothalamic STAT3 signaling, as measured by gel shift assay after 15 weeks of high-fat diet. Despite the absence of detectable signaling after peripheral leptin at 15 weeks, the mice fed the high-fat diet retained the capacity to respond to icv leptin, although the magnitude of STAT3 activation was substantially reduced. These results suggest that leptin resistance induced by a high-fat diet evolves during the course of the diet and has at least two independent causes: an apparent defect in access to sites of action in the hypothalamus that markedly limits the ability of peripheral leptin to activate hypothalamic STAT signaling, and an intracellular signaling defect in leptin-responsive hypothalamic neurons that lies upstream of STAT3 activation.


Breakthrough pain: definition, prevalence and characteristics.
In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.


On the nature of peptides involved in T cell alloreactivity.
The strong reaction of T cells against foreign major histocompatibility complex (MHC) antigens, commonly termed "alloreactivity", is not only a nuisance for clinical organ transplantation; it also remains a puzzling question for immunologists. By making use of recent technical developments, alloreactive T cells nominally directed against a mutation in a single MHC class I molecule were found to fall into several major categories. One is recognizing peptides whose occurrence is dependent on one particular MHC allele, another is recognizing peptides supported by several MHC alleles, and a third is recognizing peptides occurring independently of MHC alleles. In a fourth category, the binding to MHC of any of a broad range of peptides appears sufficient. In addition, there are T cells for which no peptide involvement could be detected at all. Even within these categories, the heterogeneity of T cells is considerable: among 16 Kb-reactive T cells analyzed, 15 different modes of reactions were found.


Incidence of hypertension and non-insulin dependent diabetes mellitus and associated risk factors in a rapidly developing Caribbean community: the St James survey, Trinidad.
To compare the incidence rates of hypertension and non-insulin dependent diabetes mellitus in relation to ethnicity and other characteristics in a rapidly developing community. Prospective surveillance of a total community for five years. Cohort of 2491 men and women aged 35 to 69 years (79% response), of African, Indian and "other' (mainly Afro-European) descent. During surveillance, secular increases occurred in fasting blood glucose concentrations in both sexes and in body mass index (BMI) in men, with apparent secular reductions in systolic blood pressure in both sexes. Incidence rates of hypertension did not differ significantly with ethnicity, ranging between 33 and 41 per 1000 person-years in men and between 27 and 32 per 1000 person-years in women. In men, the incidence of diabetes (per 1000 person-years) in Indians (24) was significantly higher than in Africans (13) and others (11). In women, the diabetic incidence was similar to that for men in Indians (23) and Africans (14), but in others was twice that in men (21). In both sexes, weight gain was an important risk factor for hypertension, whereas risk of diabetes increased with BMI at baseline. The increased risk of diabetes in Indians among men was independent of baseline BMI and blood glucose. Apart from the increased risk of diabetes in Indians, ethnicity had no significant influence on incidence rates of hypertension and diabetes in Trinidad. Secular increases in blood glucose in both sexes and in BMI in men probably contributed to the concurrent increase in mortality from coronary heart disease in this community.


Numerical analysis and synthesis of 2D quasi-optical reflectors and beam waveguides based on an integral-equation approach with Nystrom's discretization.
Considered is the beam wave guidance and scattering by 2D quasi-optical reflectors modeling the components of beam waveguides. The incident field is taken as the complex-source-point field to simulate a finite-width beam generated by a small-aperture source. A numerical solution is obtained from the coupled singular integral equations (SIEs) for the surface currents on reflectors, discretized by using the recently introduced Nystrom-type quadrature formulas. This analysis is applied to study what effect the edge illumination has on the performance of a chain of confocal elliptic reflectors. We also develop a semianalytical approach for shaped reflector synthesis after a prescribed near-field pattern. Here a new point is the use of auxiliary SIEs of the same type as in the scattering analysis problem, however, for the gradient of the objective function. Sample results are presented for the synthesis of a reflector-type beam splitter.


A Feathered Dinosaur Tail with Primitive Plumage Trapped in Mid-Cretaceous Amber.
In the two decades since the discovery of feathered dinosaurs [1-3], the range of plumage known from non-avialan theropods has expanded significantly, confirming several features predicted by developmentally informed models of feather evolution [4-10]. However, three-dimensional feather morphology and evolutionary patterns remain difficult to interpret, due to compression in sedimentary rocks [9, 11]. Recent discoveries in Cretaceous amber from Canada, France, Japan, Lebanon, Myanmar, and the United States [12-18] reveal much finer levels of structural detail, but taxonomic placement is uncertain because plumage is rarely associated with identifiable skeletal material [14]. Here we describe the feathered tail of a non-avialan theropod preserved in mid-Cretaceous (∼99 Ma) amber from Kachin State, Myanmar [17], with plumage structure that directly informs the evolutionary developmental pathway of feathers. This specimen provides an opportunity to document pristine feathers in direct association with a putative juvenile coelurosaur, preserving fine morphological details, including the spatial arrangement of follicles and feathers on the body, and micrometer-scale features of the plumage. Many feathers exhibit a short, slender rachis with alternating barbs and a uniform series of contiguous barbules, supporting the developmental hypothesis that barbs already possessed barbules when they fused to form the rachis [19]. Beneath the feathers, carbonized soft tissues offer a glimpse of preservational potential and history for the inclusion; abundant Fe2+ suggests that vestiges of primary hemoglobin and ferritin remain trapped within the tail. The new finding highlights the unique preservation potential of amber for understanding the morphology and evolution of coelurosaurian integumentary structures.


A comprehensive analysis of small-passerine fatalities from collision with turbines at wind energy facilities.
Small passerines, sometimes referred to as perching birds or songbirds, are the most abundant bird group in the United States (US) and Canada, and the most common among bird fatalities caused by collision with turbines at wind energy facilities. We used data compiled from 116 studies conducted in the US and Canada to estimate the annual rate of small-bird fatalities. It was necessary for us to calculate estimates of small-bird fatality rates from reported all-bird rates for 30% of studies. The remaining 70% of studies provided data on small-bird fatalities. We then adjusted estimates to account for detection bias and loss of carcasses from scavenging. These studies represented about 15% of current operating capacity (megawatts [MW]) for all wind energy facilities in the US and Canada and provided information on 4,975 bird fatalities, of which we estimated 62.5% were small passerines comprising 156 species. For all wind energy facilities currently in operation, we estimated that about 134,000 to 230,000 small-passerine fatalities from collision with wind turbines occur annually, or 2.10 to 3.35 small birds/MW of installed capacity. When adjusted for species composition, this indicates that about 368,000 fatalities for all bird species are caused annually by collisions with wind turbines. Other human-related sources of bird deaths, (e.g., communication towers, buildings [including windows]), and domestic cats) have been estimated to kill millions to billions of birds each year. Compared to continent-wide population estimates, the cumulative mortality rate per year by species was highest for black-throated blue warbler and tree swallow; 0.043% of the entire population of each species was estimated to annually suffer mortality from collisions with turbines. For the eighteen species with the next highest values, this estimate ranged from 0.008% to 0.038%, much lower than rates attributed to collisions with communication towers (1.2% to 9.0% for top twenty species).


Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine ischemia in the fetal rat brain: ultrastructural evaluation.
The aim of this study was to investigate the neuroprotective effect of magnesium sulfate and dexamethasone on oxidative damage in intrauterine ischemia. In this study, 19-day pregnant rats were divided into five groups. Fetal brain ischemia was achieved in the ischemia/ reperfusion (I/R) group by bilaterally closing the utero-ovarian artery with aneurysm clips for 30 min and subsequently removing the aneurysm clips for 60 min for reperfusion. Mg (600 mg/kg) and dexamethasone (0.25 mg/kg) were administered 20 min before the I/R insult. The lipid peroxidation in the brain tissue was determined by the concentration of thiobarbituric acid reactive substances (TBARS). The mitochondrial score was calculated after an evaluation with electron microscopy. Both the electron microscope and TBARS data showed a significant difference between the control and I/R groups. The Mg and dexamethasone treatment groups exhibited significantly lower TBARS values compared to the IR group. Similarly, the mitochondrial scores in the Mg and dexamethasone treatment groups were significantly lower than those in the I/R group. Result showed that magnesium sulfate and dexamethasone prevent lipid peroxidation and reduce mitochondrial injury thus suggests neuroprotective effects in fetal rat brain in intrauterine ischemia-reperfusion (I/R) injury.


Personal health records: an evaluation.
A cohort of mothers whose babies were born over one calendar month were followed up eight to 11 months after being given a personal health record for their newborn babies. Eight per cent of mothers lost the records and three more said they had not been given a record while in hospital; a total of 10% of mothers had either lost or misplaced the record. There were no particular demographic characteristics which identified the mothers who were more likely to lose the record. Most parents liked personal health records and used them frequently, as did the community health staff. Most private doctors, however, did not find them useful. Before wider distribution of such records is contemplated health workers should be adequately prepared, especially doctors in the private sector.


Developing medical students as teachers: an anatomy-based student-as-teacher program with emphasis on core teaching competencies.
Teaching is an increasingly recognized responsibility of the resident physician. Residents, however, often assume teaching responsibilities without adequate preparation. Consequently, many medical schools have implemented student-as-teacher (SAT) programs that provide near-peer teaching opportunities to senior medical students. Near-peer teaching is widely regarded as an effective teaching modality; however, whether near-peer teaching experiences in medical school prepare students for the teaching demands of residency is less understood. We explored whether the anatomy-based SAT program through the Human Structure didactic block at Mayo Medical School addressed the core teaching competencies of a medical educator and prepared its participants for further teaching roles in their medical careers. A web-based survey was sent to all teaching assistants in the anatomy-based SAT program over the past five years (2007-2011). Survey questions were constructed based on previously published competencies in seven teaching domains--course development, course organization, teaching execution, student coaching, student assessment, teacher evaluation, and scholarship. Results of the survey indicate that participants in the anatomy-based SAT program achieved core competencies of a medical educator and felt prepared for the teaching demands of residency.


A community education monitoring system: methods from the Stanford Five-City Project, the Minnesota Heart Health Program and the Pawtucket Heart Health Program.
Understanding the process of behavior change interventions is critical to achieving campaign effectiveness and successful program replication. The present article presents a community education monitoring system (CEMS) using data from the Stanford Five-City Project (FCP), the Minnesota Heart Health Program (MHHP) and the Pawtucket Heart Health Program (PHHP). CEMS records the number and type of intervention activities, outcome objectives, targets of change (individual, organizational or environmental), channel(s) of dissemination and proportion of programs funded by the community. These data illustrate (1) the application of theory for each project, (2) data-based program administration, (3) feedback for revising programs and (4) type of reach or 'dose' information obtained from intervention monitoring. Process evaluations such as CEMS provide critical links between field realities and evaluation outcomes. This type of evaluation develops standards for measuring program reach and allows comparisons with other programs. CEMS also illustrates how programs enact theory. Validation studies are critical to the continued successful use of CEMS. The first step, however, is to develop a uniform way of describing complex multichannel behavior change programs. CEMS in a refined form should prove invaluable to health promotion program planners whether in research or service settings.


Crystal structure of the ligand-binding domain of the promiscuous EphA4 receptor reveals two distinct conformations.
Eph receptors and their ephrin ligands are important mediators of cell-cell communication. They are divided in two subclasses based on their affinities for each other and on sequence conservation. Receptor-ligand binding within each subclass is fairly promiscuous, while binding cross the subclasses happens rarely. EphA4 is an exception to this general rule, since it has long been known to bind both A- and B-class ephrin ligands but the reason for this exceptional behavior has not been worked out at molecular level. Recent structural and biochemical studies on EphA4 ligand-binding domain alone and in complex with its ligands have addressed this question. However, the published structures of EphA4/ephrin complexes differ considerably from each other and strikingly different explanations for the exceptional promiscuity of EphA4 were proposed. To address these contradictory findings, we have determined a crystal structure of the EphA4 ligand-binding domain at 2.3A resolution and show that the receptor has an unprecedented ability to exist in two very different, well-ordered conformations even in the unbound state. Our results suggest that the ligand promiscuity of the Ephs is directly correlated with the structural flexibility of the ligand-binding surface of the receptor.


Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.
This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern. In the past, it has been difficult to associate EADs or reentry with the undulating electrocardiographic (ECG) patterns of TDP. A voltage-sensitive dye was used for high resolution video imaging of electrical waves on the epicardial and endocardial surface of the Langendorff-perfused rabbit heart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node. Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean +/- SEM] 194 +/- 12 vs. 132 +/- 8 ms, p < 0.03). Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing-induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.


Prehospital Emergency Nursing students' experiences of learning during prehospital clinical placements.
Clinical placements play an important role in learning a new profession, but students report about poor placement experiences. Standards have been laid down for improvements within clinical training in Prehospital Emergency Nursing programmes in Sweden, but no studies have been carried out in this field in a Swedish context. The purpose of this study was thus to describe the experiences of Prehospital Emergency Nursing (PEN) students of their clinical placement and the effect on their learning process. Data were collected in 28 individual interviews and analyzed in accordance with Flanagan's Critical Incident Technique. Three main areas emerged: the professional clinical supervisor, the clinical placement setting and the learning strategy. All these areas played a significant role in the PEN students' learning progress and development into a new professional role. The choice of clinical supervisor (CS) and clinical placement is important if PEN students' learning is to be an effective and positive experience. The prehospital environment is unique and can have positive and negative effects on student learning depending on the support and structure given during their clinical placement. A learning strategy based on reflective dialogue, CS continuity and a learning structure based on the prehospital environment is presented.


Treatment of Burn and Surgical Wounds With Recombinant Human Tropoelastin Produces New Elastin Fibers in Scars.
Tropoelastin (TE), the soluble precursor of insoluble elastin fibers, is produced in minimal amounts in adults. Burn injuries result in inflexible collagen-rich scars because of lack of elastin fiber formation. We studied the feasibility of using recombinant human tropoelastin to enable elastin fiber production in burn and surgical scars to improve skin flexibility. In a swine hypertrophic burn scar model, normal skin and 3 × 3-cm partial thickness thermal burns underwent dermatome resection at 1 week post burn and randomized to four subcutaneous injections of saline or TE (either 0.5, 5, or 10 mg/ml) spaced 3 days apart. Two burn sites received TE injections after wound closure (0.5 or 10 mg/ml). At 90 days, skin hardness, flexibility, and histology were evaluated. All injury sites developed hypertrophic scars. New elastin fibers were found in burn scars in all injuries injected after skin closure with low (5/5) and high (6/6) TE doses (P < .05). No elastin fibers were observed without TE treatment. No significant differences in skin hardness, flexibility, or inflammation were observed. This is the first report demonstrating that subcutaneous injections of TE into surgical and burn injuries can safely produce new elastin fibers in scars. Despite the development of new elastin fibers, skin flexibility was not improved, possibly because of insufficient elastin fiber maturation or the hypertrophic model used. The ability to restore elastin fiber formation in adult skin after burns, trauma, and surgery may improve skin regeneration and reduce disabling complications of scar formation.


Cost-effectiveness of prophylactic magnesium sulphate for 9996 women with pre-eclampsia from 33 countries: economic evaluation of the Magpie Trial.
To assess the cost-effectiveness of using magnesium sulphate for pre-eclampsia to prevent eclampsia. Multinational trial-based economic evaluation. Thirty-three countries participating in the Magnesium Sulphate for Prevention of Eclampsia (Magpie) Trial. Women (9996) with pre-eclampsia from the Magpie Trial. Outcome and hospital resource use data were available for the trial period from the Magpie Trial. Country-specific unit costs (U.S. dollar, year 2001) were obtained subsequently from participating hospitals by questionnaire. Cost-effectiveness was estimated for three categories of countries grouped by gross national income (GNI) into high, middle and low GNI countries using a regression model. Uncertainty was explored in sensitivity analyses. Eclampsia, hospital care costs and the incremental cost per case of eclampsia prevented. The number of women with pre-eclampsia who needed to receive magnesium sulphate to prevent one case of eclampsia was 324 [95% confidence interval (CI) 122, infinity] in high, 184 (95% CI 91, 6798) in middle and 43 (95% CI 30, 68) in low GNI countries. The additional hospital care cost per woman receiving magnesium sulphate was $65, $13 and $11, respectively. The incremental cost of preventing one case of eclampsia was $21,202 in high, $2473 in middle and $456 in low GNI countries. Reserving treatment for severe pre-eclampsia would lower these estimates to $12,942, $1179 and $263. Magnesium sulphate for pre-eclampsia costs less and prevents more eclampsia in low GNI than in high GNI countries. Cost-effectiveness substantially improves if it is used only for severe pre-eclampsia, or the purchase price is reduced in low GNI countries.


Dactinomycin impairs cellular respiration and reduces accompanying ATP formation.
The effect of dactinomycin on cellular respiration and accompanying ATP formation was investigated in Jurkat and HL-60 cells. Cellular mitochondrial oxygen consumption (measured by a homemade phosphorescence analyzer) and ATP content (measured by the luciferin-luciferase bioluminescence system) were determined as functions of time t during continuous exposure to the drug. The rate of respiration, k, was the negative of the slope of [O2] versus t. Oxygen consumption and ATP content were diminished by cyanide, confirming that both processes involved oxidations in the mitochondrial respiratory chain. In the presence of dactinomycin, k decreased gradually with t, the decrease being more pronounced at higher drug concentrations. Cellular ATP remained constant for 5 h in untreated cells, but in the presence of 20 microM dactinomycin it decreased gradually (to one-tenth the value at 5 h for untreated cells). The drug-induced inhibition of respiration and decrease in ATP were blocked by the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethyl ketone (zVAD-fmk). A rapid but temporary decrease in cellular ATP observed on the addition of zVAD-fmk was shown to be due to DMSO (added with zVAD-fmk). The effect of dactinomycin on respiration differed from that of doxorubicin. Plots of [O2] versus t were curved for dactinomycin so that k decreased gradually with t. The corresponding plots for doxorubicin were well fit by two straight lines; so k was constant for approximately 150 min, at which time k decreased, remaining constant at a lower level thereafter. The results for cells treated with mixtures of the two drugs indicated that the drugs acted synergistically. These results show the onset and severity of mitochondrial dysfunction in cells undergoing apoptosis induced by dactinomycin.


STUDIES ON ARTIFICIAL ANTIGENS. III. THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO HAPTEN-POLY-L-LYSINE CONJUGATES IN GUINEA PIGS.
The genetic transmission of the capacity to develop an immune response to hapten-polylysine conjugates was studied in guinea pigs. 82 per cent of the 22 offspring of 8 pairs of responder (guinea pigs which are capable of an immune response) parents were also responders, whereas, none of the 26 offspring of 9 pairs of non-responder parents were responders. None of 11 strain 13 guinea pigs and 100 per cent of 40 strain 2 guinea pigs were responders. These findings are consistent with the view that the capacity to respond immunologically to hapten-polylysine conjugates is genetically transmitted as a unigenic Mendelian dominant.


Association between prepayment systems and emergency medical services use among patients with acute chest discomfort syndrome.
Cost concerns may inhibit emergency medical services (EMS) use. Novel tax-based and subscription prepayment programs indemnify patients against the cost of EMS treatment and transport. We determine whether the presence of (or enrollment in) prepayment plans increase EMS use among patients with acute chest discomfort, particularly those residing in low-income areas, those lacking private insurance, or both. This study uses a subset of baseline data from the REACT trial, a multicenter, randomized controlled community trial designed, in part, to increase EMS use. The sample includes 860 consecutive noninstitutionalized patients (>30 years old) presenting with nontraumatic chest discomfort to hospital emergency departments in 4 Oregon/Washington communities. The association between prepayment systems and EMS use was analyzed using multivariable logistic regression. Overall EMS use was 52% (n=445). Among EMS users, 338 (75%) were subsequently admitted to the hospital and 110 (25%) were released from the ED. Prepayment was not associated with increased EMS use in the overall patient sample. However, patients residing in low-income census block groups (median annual income <$30,000) were 2.6 times (95% confidence interval [CI] 1.4 to 4.8) more likely to use EMS when a prepayment system was available than when no system was present. No association was noted among higher-income block group residents. Among low-income block group residents lacking private insurance, prepayment systems were associated with 3.8 times (95% CI 1.2 to 13.4) greater EMS usage. Economic considerations may affect EMS system utilization among underinsured and low-income patients experiencing a cardiac event. Prepayment systems may increase EMS utilization among these groups. [Seipmann DB, Mann NC, Hedges JR, Daya MR, for the Rapid Early Action for Coronary Treatment (REACT) Study. Association between prepayment systems and emergency medical services use among patients with acute chest discomfort syndrome. Ann Emerg Med. June 2000;35:573-578.].


Fish intelligence, sentience and ethics.
Fish are one of the most highly utilised vertebrate taxa by humans; they are harvested from wild stocks as part of global fishing industries, grown under intensive aquaculture conditions, are the most common pet and are widely used for scientific research. But fish are seldom afforded the same level of compassion or welfare as warm-blooded vertebrates. Part of the problem is the large gap between people's perception of fish intelligence and the scientific reality. This is an important issue because public perception guides government policy. The perception of an animal's intelligence often drives our decision whether or not to include them in our moral circle. From a welfare perspective, most researchers would suggest that if an animal is sentient, then it can most likely suffer and should therefore be offered some form of formal protection. There has been a debate about fish welfare for decades which centres on the question of whether they are sentient or conscious. The implications for affording the same level of protection to fish as other vertebrates are great, not least because of fishing-related industries. Here, I review the current state of knowledge of fish cognition starting with their sensory perception and moving on to cognition. The review reveals that fish perception and cognitive abilities often match or exceed other vertebrates. A review of the evidence for pain perception strongly suggests that fish experience pain in a manner similar to the rest of the vertebrates. Although scientists cannot provide a definitive answer on the level of consciousness for any non-human vertebrate, the extensive evidence of fish behavioural and cognitive sophistication and pain perception suggests that best practice would be to lend fish the same level of protection as any other vertebrate.


Protecting healthcare workers from pandemic influenza: N95 or surgical masks?
The successful management of an influenza pandemic will be reliant on the expertise of healthcare workers at high risk for occupationally acquired influenza. Recommended infection control measures for healthcare workers include surgical masks to protect against droplet-spread respiratory transmissible infections and N95 masks to protect against aerosol-spread infections. A literature review was undertaken for evidence of superior protective value of N95 masks or surgical masks for healthcare workers against influenza and extraneous factors influencing conferred protection. Four scientific search engines using 12 search sequences identified 21 mask studies in healthcare settings for the prevention of transmission of respiratory syncytial virus, Bordetella pertussis, and severe acute respiratory syndrome. Each was critically assessed in accordance with Australian National Health Medical Research Council guidelines. An additional 25 laboratory-based publications were also reviewed. All studies reviewed used medium or lower level evidence study design. In the majority of studies, important confounders included the unrecognized impact of concurrent bundling of other infection control measures, mask compliance, contamination from improper doffing of masks, and ocular inoculation. Only three studies directly compared the protective value of surgical masks with N95 masks. The majority of laboratory studies identified both mask types as having a range of filtration efficiency, yet N95 masks afford superior protection against particles of a similar size to influenza. World Health Organization guidelines recommend surgical masks for all patient care with the exception of N95 masks for aerosol generating procedures. Because of the paucity of high-quality studies in the healthcare setting, the advocacy of mask types is not entirely evidence-based. Evidence from laboratory studies of potential airborne spread of influenza from shedding patients indicate that guidelines related to the current 1-meter respiratory zone may need to be extended to a larger respiratory zone and include protection from ocular inoculation.


Revisiting the Role of Cultural Capital in East Asian Educational Systems: The Case of South Korea.
The concept of cultural capital has proved invaluable in understanding educational systems in Western countries, and recent work seeks to extend those insights to the diverse educational systems of other geographic regions. We explored cultural capital in South Korea by investigating the relationships among family socioeconomic status (SES), cultural capital, and children's academic achievement using data from the 2000 Programme for International Student Assessment. South Korea was compared with Japan, France, and the United States to understand how institutional features of South Korean education shape the role of cultural capital in academic success. Results showed that family SES had a positive effect on both parental objectified cultural capital and children's embodied cultural capital in South Korea, consistent with evidence from the other countries. Moreover, parental objectified cultural capital had a positive effect on children's academic achievement in South Korea. In contrast to other countries, however, children's embodied cultural capital had a negative effect on academic achievement in South Korea controlling for the other variables. We highlighted several institutional features of South Korean education including a standardized curriculum, extreme focus on test preparation, and extensive shadow education, which may combine to suppress the effect of children's embodied cultural capital on academic achievement.


The human cytomegalovirus UL82 gene product (pp71) accelerates progression through the G1 phase of the cell cycle.
As viruses are reliant upon their host cell to serve as proper environments for their replication, many have evolved mechanisms to alter intracellular conditions to suit their own needs. For example, human cytomegalovirus induces quiescent cells to enter the cell cycle and then arrests them in late G(1), before they enter the S phase, a cell cycle compartment that is presumably favorable for viral replication. Here we show that the protein product of the human cytomegalovirus UL82 gene, pp71, can accelerate the movement of cells through the G(1) phase of the cell cycle. This activity would help infected cells reach the late G(1) arrest point sooner and thus may stimulate the infectious cycle. pp71 also induces DNA synthesis in quiescent cells, but a pp71 mutant protein that is unable to induce quiescent cells to enter the cell cycle still retains the ability to accelerate the G(1) phase. Thus, the mechanism through which pp71 accelerates G(1) cell cycle progression appears to be distinct from the one that it employs to induce quiescent cells to exit G(0) and subsequently enter the S phase.


Effects of workers' compensation on the diagnosis and surgical treatment of patients with hand and wrist disorders.
Workers' Compensation differs from standard insurance, and it is unclear how or if Workers' Compensation insurance influences the diagnosis and treatment of hand and wrist disorders. The aim of this study was to compare the diagnosis and course of treatment of hand disorders between patients with Workers' Compensation insurance and patients with standard insurance. The complete medical records of patients who visited an academic orthopaedic hand clinic between January 2005 and January 2007 were reviewed, and information on patient history, utilization of diagnostic tests, diagnosis, surgery, and wait-time to surgery was collected. Patients with Workers' Compensation insurance and those with other, third-party coverage were analyzed and compared. Patients without insurance were excluded from this study. 1413 patients (representing 2121 diagnoses) were included in the study. One hundred and sixteen patients (8%) had Workers' Compensation insurance and 1297 patients (92%) had standard insurance. Patients with Workers' Compensation insurance were younger than patients with standard insurance (mean age, forty-three years compared with fifty years, respectively; p < 0.05) and were also more likely to be male (50% compared with 40%, respectively; p = 0.04). Generally, Workers' Compensation patients more often had neurological conditions (p < 0.01), but there was no significant difference in the most common diagnoses between the two groups. Patients with Workers' Compensation underwent surgery slightly more often than did patients with standard insurance (44% compared with 35%, respectively; p = 0.07) and had a higher average number of visits before undergoing surgery (2.3 visits compared with 1.2 visits, respectively; p < 0.05). Twenty-three (45%) of the fifty-one patients with Workers' Compensation insurance who received a diagnosis indicating the need for surgery underwent surgery after the first visit, compared with 316 (69%) of 458 patients with standard insurance (p < 0.05). Patients with Workers' Compensation insurance were more likely than patients with standard insurance to undergo electrodiagnostic testing (26% compared with 15%, respectively; p < 0.01) or magnetic resonance imaging (16% compared with 9%, respectively; p = 0.02). Compared with patients receiving standard insurance, patients receiving Workers' Compensation insurance have a greater number of clinic visits before undergoing surgery and receive more diagnostic testing. More research is needed to explore these differences and their potential clinical and economic consequences.


Hypoxia-inducible regulation of a prodrug-activating enzyme for tumor-specific gene therapy.
Previous studies have suggested that tumor hypoxia could be exploited for cancer gene therapy. Using hypoxia-responsive elements derived from the human vascular endothelial growth factor gene, we have generated vectors expressing a bacterial nitroreductase (NTR) gene that can activate the anticancer prodrug CB1954. Stable transfectants of human HT1080 tumor cells with hypoxia-inducible vectors were established with G418 selection. Hypoxic induction of NTR protein correlated with increased sensitivity to in vitro exposure of HT1080 cells to the prodrug. Growth delay assays were performed with established tumor xenografts derived from the same cells to detect the in vivo efficacy of CB1954 conversion to its cytotoxic form. Significant antitumor effects were achieved with intraperitoneal injections of CB1954 both in tumors that express NTR constitutively or with a hypoxia-inducible promoter. In addition, respiration of 10% 02 increased tumor hypoxia in vivo and enhanced the antitumor effects. Taken together, these results demonstrate that hypoxia-inducible vectors may be useful for tumor-selective gene therapy, although the problem of delivery of the vector to the tumors, particularly to the hypoxic cells in the tumors, is not addressed by these studies.


Towards a global environmental sociology? Legacies, trends and future directions.
A current debate on environmental sociology involves how the subdiscipline should conceptualise and investigate the environment and whether it should be prescriptive and deliver policy recommendations. Taking this debate as a point of departure this article discusses the current and future role of sociology in a globalised world. It discusses how environmental sociology in the US and Europe differ in their understandings of sociology's contribution to the study of the environment. Particular stress is placed on how these two regions differ with respect to their use of the tradition of sociological thought, views on what constitutes the environment and ways of institutionalising environmental sociology as a sociological field. In conclusion, the question is raised of whether current versions of environmental sociology are appropriate for analysing a globalised world environment; or whether environmental sociology's strong roots in European and US cultures make it less relevant when facing an increasingly globalised world. Finally, the article proposes some new rules for a global environmental sociology and describes some of their possible implications for the sociological study of climate change.


Vascularization Potential of Electrospun Poly(L-Lactide-co-Caprolactone) Scaffold: The Impact for Tissue Engineering.
BACKGROUND Electrospun nanofibers have widespread putative applications in the field of regenerative medicine and tissue engineering. When compared to naturally occurring collagen matrices, electrospun nanofiber scaffolds have two distinct advantages: they do not induce a foreign body reaction and they are not at risk for biological contamination. However, the exact substrate, structure, and production methods have yet to be defined. MATERIAL AND METHODS In the current study, tubular-shaped poly(L-lactide-co-caprolactone) (PLCL) constructs produced using electrospinning technology were evaluated for their potential application in the field of tissue regeneration in two separate anatomic locations: the skin and the abdomen. The constructs were designed to have an internal diameter of 3 mm and thickness of 200 μm. Using a rodent model, 20 PLCL tubular constructs were surgically implanted in the abdominal cavity and subcutaneously. The constructs were then evaluated histologically using electron microscopy at 6 weeks post-implantation. RESULTS Histological evaluation and analysis using scanning electron microscopy showed that pure scaffolds by themselves were able to induce angiogenesis after implantation in the rat model. Vascularization was observed in both tested groups; however, better results were obtained after intraperitoneal implantation. Formation of more and larger vessels that migrated inside the scaffold was observed after implantation into the peritoneum. In this group no evidence of inflammation and better integration of scaffold with host tissue were noticed. Subcutaneous implantation resulted in more fibrotic reaction, and differences in cell morphology were also observed between the two tested groups. CONCLUSIONS This study provides a standardized evaluation of a PLCL conduit structure in two different anatomic locations, demonstrating the excellent ability of the structure to achieve vascularization. Functional, histological, and mechanical data clearly indicate prospective clinical utilization of PLCL in critical size defect regeneration.


Tibial tuberosity fracture as a complication of tibial tuberosity advancement.
To retrospectively compare two clinical subsets of dogs suffering tibial tuberosity (TT) fracture (incidental finding or sudden onset severe lameness) as a complication of tibial tuberosity advancement (TTA) and to report the surgical management and outcome of TT fracture as a complication of TTA. The medical records of 10 dogs with eleven TT fractures or crest fractures after TTA were reviewed. The outcome and complications were determined from clinical and radiographic follow-up examinations. Limb function was evaluated between six and 12 weeks postoperatively. Owners were contacted by phone for long-term follow-up at least six months after the last examination. Four dogs required surgical stabilization and six dogs had conservative management. In the surgical group, every case experienced a sudden non-weight-bearing lameness after the initial TTA surgery. In three of the four cases an attempt was made to stabilize the TT and crest fracture while maintaining the TT advancement. Postoperative complications were encountered in three of the four surgically treated cases. Functional outcome was considered excellent in seven cases and good in the other three. Tibial tuberosity fracture is a complication of TTA that seems to have a favourable prognosis, although it can result in significant morbidity and in some cases revision surgery may be required.


Triple-halide wide-band gap perovskites with suppressed phase segregation for efficient tandems.
Wide-band gap metal halide perovskites are promising semiconductors to pair with silicon in tandem solar cells to pursue the goal of achieving power conversion efficiency (PCE) greater than 30% at low cost. However, wide-band gap perovskite solar cells have been fundamentally limited by photoinduced phase segregation and low open-circuit voltage. We report efficient 1.67-electron volt wide-band gap perovskite top cells using triple-halide alloys (chlorine, bromine, iodine) to tailor the band gap and stabilize the semiconductor under illumination. We show a factor of 2 increase in photocarrier lifetime and charge-carrier mobility that resulted from enhancing the solubility of chlorine by replacing some of the iodine with bromine to shrink the lattice parameter. We observed a suppression of light-induced phase segregation in films even at 100-sun illumination intensity and less than 4% degradation in semitransparent top cells after 1000 hours of maximum power point (MPP) operation at 60°C. By integrating these top cells with silicon bottom cells, we achieved a PCE of 27% in two-terminal monolithic tandems with an area of 1 square centimeter.


Range-wide phylogeographic analysis of the spotted frog complex (Rana luteiventris and Rana pretiosa) in northwestern North America.
The dynamic geological and climatic history of northwestern North America has made it a focal region for phylogeography. We conducted a range-wide phylogeographic analysis of the spotted frog complex (Rana luteiventris and Rana pretiosa) across its range in northwestern North America to understand its evolutionary history and the distribution of clades to inform conservation of R. pretiosa and Great Basin R. luteiventris, candidates for listing under the US Endangered Species Act. Mitochondrial DNA sequence data from a segment of the cytochrome b gene were obtained from 308 R. luteiventris and R. pretiosa from 96 sites. Phylogenetic analysis revealed one main R. pretiosa clade and three main R. luteiventris clades, two of which overlapped in southeastern Oregon. The three R. luteiventris clades were separated from each other by high levels of sequence divergence (average of 4.75-4.97%). Two divergent clades were also uncovered within the Great Basin. Low genetic variation in R. pretiosa and the southeastern Oregon clade of R. luteiventris suggests concern about their vulnerability to extinction.


Severe theophylline toxicity. Role of conservative measures, antiarrhythmic agents, and charcoal hemoperfusion.
The presenting symptoms, course, and treatment of 10 patients with severe theophylline toxicity (heart rate above 120, multifocal atrial tachycardia or premature ventricular contractions, hypotension, seizures) are described. Theophylline levels at presentation averaged 66 micrograms/ml (range 30 to 180 micrograms/ml). All patients had marked tachycardia; 80 percent had gastrointestinal symptoms, 50 percent were hypotensive, and 20 percent had seizures. A known history of poor compliance or other risk factors to overdosage was present in 60 percent. Of the five patients in whom drug clearances were determined, two had uniform first-order drug elimination. Three had biphasic elimination with an initial period of delayed elimination due to either zero-order kinetics or continued drug absorption. During the first-order elimination period, mean plasma theophylline clearance was 28.0 +/- 4.3 ml per minute with a half-life of 8.2 hours. In the patients with initially delayed elimination, the mean clearance during the slow phase was 9.6 +/- 3.3 ml per minute with an apparent half-life of 31 hours. One patient was treated with charcoal hemoperfusion but the others received conservative management alone; all recovered without permanent sequelae. Propranolol and verapamil were useful in controlling supraventricular tachycardia. It appears that most patients with severe theophylline toxicity can be managed without hemoperfusion, which should be considered only when drug clearance is reduced, and hypotension, tachycardia, ventricular ectopy, or seizures are refractory to conservative measures.