Surveying Over the Counter and Prescription Only Medication Misuse in Treatment Services During COVID-19.
A greater understanding of Over the Counter (OTC) and Prescription Only Medication (POM) misuse amongst adults accessing substance misuse services (SMS) during COVID-19 is required to identify how SMS can better meet the needs of the people who require treatment. To use a questionnaire to explore OTC/POM misuse during COVID-19 in adults accessing community SMS in England. In 2020 to 2021 anonymous self-administered online/paper questionnaires which collated quantitative and qualitative data were completed. They were piloted for suitability and ethical approval was obtained. Thematic analysis was conducted for qualitative data and chi-square tests used to assess the relationship between quantitative variables. Participants were Caucasian (94.6% British), majority male (58.9%), aged 18 to 61 years. Most were prescribed medication for problematic substance use, with a 92.5% self-reported adherence rate. The misuse of benzodiazepines (22.2%) codeine products (30.8%) and pregabalin (14.5%) predominated and 37.5% misused 2 or more medicines. Administration was usually oral and concomitant use of other substances was common: alcohol 44.6% (52% daily), tobacco/vaping 73.2% and illicit substances 58.9%. There were statistically significant associations identified, including between changes during COVID-19 to OTC/POM misuse and illicit use. Only 56 questionnaires were included in the analysis: we believe this low number was because of infection control measures, limited footfall in services, pressures on staff limiting their capacity to distribute the paper questionnaires and reliance upon telephone consultations limiting online distribution. Increasing OTC/POM misuse and obtaining illicit supplies were reported when access to usual supplies were restricted; however, changes to doses/dispensing arrangement liberalisation in response to COVID-19 were positively viewed. OTC/POM misuse, including polypharmacy and concomitant use of other substances occurred during COVID-19: SMS need to be vigilant for these issues and mitigate the associated risks for example with harm reduction interventions. Further qualitative research is required to explore the issues identified.


Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage.
We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.


Prevention, diagnosis, and treatment of opioid use disorder under the supervision of opioid stewardship programs: it's time to act now.
The third opium war may have already started, not only due to illicit opioid trafficking from the Golden Crescent and Golden Triangle on the international front but also through indiscriminate opioid prescription and opioid diversion at home. Opioid use disorder (OUD), among unintentional injuries, has become one of the top 4 causes of death in the United States (U.S.). An OUD is defined as a problematic pattern of opioid use resulting in clinically significant impairment or distress, consisting of 2 or more of 11 problems within 1 year, as described by the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Observation of aberrant behaviors of OUD is also helpful for overworked clinicians. For the prevention of OUD, the Opioid Risk Tool and the Current Opioid Misuse Measure are appropriate screening tests before and during opioid administration, respectively. Treatment of OUD consists of 3 opioid-based U.S. Food and Drug Administration-approved medications, including methadone, buprenorphine, and naltrexone, and non-opioid-based symptomatic medications for reducing opioid withdrawal syndromes, such as α2 agonists, β-blockers, antidiarrheals, antiemetics, non-steroidal anti-inflammatory drugs, and benzodiazepines. There are at least 6 recommendable guidelines and essential terms related to OUD. Opioid stewardship programs are now critical to promoting appropriate use of opioid medications, improving patient outcomes, and reducing misuse of opioids, influenced by the successful implementation of antimicrobial stewardship programs. Despite the lack of previous motivation, now is the critical time for trying to reduce the risk of OUD.


Antagonistic regulation of Yan nuclear export by Mae and Crm1 may increase the stringency of the Ras response.
Phosphorylation of Yan, a major target of Ras signaling, leads to Crm1-dependent Yan nuclear export, a response that is regulated by Yan polymerization. Yan SAM (sterile alpha motif) domain mutations preventing polymerization result in Ras-independent, but Crm1-dependent Yan nuclear export, suggesting that polymerization prevents Yan export. Mae, which depolymerizes Yan, competes with Crm1 for binding to Yan. Phosphorylation of Yan favors Crm1 in this competition and counteracts inhibition of nuclear export by Mae. These findings suggest that, prior to Ras activation, the Mae/Yan interaction blocks premature nuclear export of Yan monomers. After activation, transcriptional up-regulation of Mae apparently leads to complete depolymerization and export of Yan.


Reliable synaptic connections between pairs of excitatory layer 4 neurones within a single 'barrel' of developing rat somatosensory cortex.
1. Dual whole-cell recordings were made from pairs of synaptically coupled excitatory neurones in the 'barrel field' in layer (L) 4 in slices of young (postnatal day 12-15) rat somatosensory cortex. The majority of interconnected excitatory neurones were spiny stellate cells with an asymmetrical dendritic arborisation largely confined to a single barrel. The remainder were star pyramidal cells with a prominent apical dendrite terminating in L2/3 without forming a tuft. 2. Excitatory synaptic connections were examined between 131 pairs of spiny L4 neurones. Single presynaptic action potentials evoked unitary EPSPs with a peak amplitude of 1.59 +/- 1.51 mV (mean +/- s. d.), a latency of 0.92 +/- 0.35 ms, a rise time of 1.53 +/- 0.46 ms and a decay time constant of 17.8 +/- 6.3 ms. 3. At 34-36 C, the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0. 37 +/- 0.16 and the percentage of failures to evoke an EPSP was 5.3 +/- 7.8 %. The c.v. and failure rate decreased with increasing amplitude of the unitary EPSP. 4. Postsynaptic glutamate receptors in spiny L4 neurones were of the AMPA and NMDA type. At -60 mV in the presence of 1 mM Mg2+, NMDA receptors contributed 39.3 +/- 12.5 % to the EPSP integral. In Mg2+-free solution, the NMDA receptor/AMPA receptor ratio of the EPSC was 0.86 +/- 0.64. 5. The number of putative synaptic contacts established by the projection neurone with the target neurone varied between two and five with a mean of 3.4 +/- 1.0 (n = 11). Synaptic contacts were exclusively found in the barrel in which the cell pair was located and were preferentially located on secondary to quarternary dendritic branches. Their mean geometric distance from the soma was 68.8 +/- 37.4 microm (range, 33.4-168.0 microm). The number of synaptic contacts and mean EPSP amplitude showed no significant correlation. 6. The results suggest that in L4 of the barrel cortex synaptic transmission between spiny neurones is largely restricted to a single barrel. The connections are very reliable, probably due to a high release probability, and have a high efficacy because of the compact structure of the dendrites and axons of spiny neurones. Intrabarrel connections thus function to amplify and distribute the afferent thalamic activity in the vertical directions of a cortical column.


Gangrenous cholecystitis due to hepatitis A infection.
A 6-year-old boy was admitted to hospital with acute gangrenous cholecystitis requiring emergency cholecystectomy. Examination of the gall-bladder revealed severe inflammation with areas of necrosis and mucosal sloughing; serology confirmed hepatitis A infection. Acute cholecystitis due to hepatitis A infection has very rarely been reported.


Brain structural damage in Friedreich's ataxia.
Neuropathological descriptions of the brain in Friedreich's ataxia (FRDA) were obtained before availability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative analysis of differences in gray matter (GM) and white matter (WM) volume. Using VBM, we assessed the brain structural damage in 22 patients with genetically confirmed FRDA and 25 healthy controls. The results were correlated with the disease duration and the severity of the patients' clinical deficits--evaluated using the International Cerebellar Ataxia Rating Scale and Inherited Ataxia Clinical Rating Scale. In patients with FRDA, VBM showed a symmetrical volume loss in dorsal medulla, infero-medial portions of the cerebellar hemispheres, the rostral vermis and in the dentate region. No volume loss in cerebral hemispheres was observed. The atrophy of the cerebellum and medulla correlated with the severity of the clinical deficit and disease duration. In patients with FRDA, significant GM and WM loss was observed only in the cerebellum and dorsal medulla. These structural changes correlate with the severity of the clinical deficit and disease duration.


Cross-linking of promoter DNA to T7 RNA polymerase does not prevent formation of a stable elongation complex.
T7 RNA polymerase recognizes a small promoter, binds DNA, and begins the process of transcription by synthesizing short RNA products without releasing promoter contacts. To determine whether the promoter contact must be released to make longer RNA products and at what position the promoter must be released, a mutant RNA polymerase was designed that allows cross-linking to a modified promoter via a covalent disulfide bond. The modifications individually have no measurable effect on transcription. Under oxidizing conditions that produce the protein-DNA cross-link, the complex is able to synthesize short RNA products, strongly supporting a model in which promoter contacts are not lost on translocation through at least position +6. However, cross-linked complexes are impaired in promoter escape in that only about one in four can escape to make full-length RNA. The remainder release 12- and 13-mer RNA transcripts, suggesting an increased energetic barrier in the transition from an initial transcribing complex to a fully competent elongation complex. The results are discussed in the context of a model in which promoter release helps drive initial collapse of the upstream edge of the bubble, which, in turn, drives initial displacement of the 5'-end of the RNA.


Factors of the medical career choice within the context of ukrainian healthcare reforms.
Introduction: The article is dedicated to the motives of medical career choice studied by Ukrainian and foreign scientists, and by the authors themselves. The authors define the main motives, grouped into the pragmatic, social, scientific and professional ones, paying particular attention to the proposed reforms of the Healthcare of Ukraine "Health 2020". The aim: The study has been aimed at detection of the medical career choice factor groups and their possible correction during the medical training, defining possible influence of the Ukrainian Healthcare reformation onto alterations of the medical career choice. Materials and methods: This article is based on bibliosemantic, dialectical, comparative, analytic, synthetic and comprehensive research methods. Review and conclusion: The authors have analyzed medical career motives according to the A. Maslow hierarchy of needs, comparing the present motives with the motives to be changed after reforming the Ukrainian healthcare. The authors conclude that according to the Maslow's hierarchy of needs, the medical career choice corresponding to the first, second and third needs level would be directly related to the pragmatic, social and scientific motives, further disappointment in career, low professional performance and professional "burnout". The career choice corresponding to the last levels of the needs hierarchy is related to the professional motives and self-actualization, but, due to the applicants' age and financial status of medical specialists in Ukraine, is not likely to occur. Positive changes in medical specialists' salary rise, social protection offered by the State and state support of the profession will provide for correction of motives onto the higher level, in this way, benefiting the patients.


Binding mode analysis of zerumbone to key signal proteins in the tumor necrosis factor pathway.
Breast cancer is the second most common cancer among women worldwide. Several signaling pathways have been implicated as causative and progression agents. The tumor necrosis factor (TNF) α protein plays a dual role in promoting and inhibiting cancer depending largely on the pathway initiated by the binding of the protein to its receptor. Zerumbone, an active constituent of Zingiber zerumbet, Smith, is known to act on the tumor necrosis factor pathway upregulating tumour necrosis factor related apoptosis inducing ligand (TRAIL) death receptors and inducing apoptosis in cancer cells. Zerumbone is a sesquiterpene that is able to penetrate into the hydrophobic pockets of proteins to exert its inhibiting activity with several proteins. We found a good binding with the tumor necrosis factor, kinase κB (IKKβ) and the Nuclear factor κB (NF-κB) component proteins along the TNF pathway. Our results suggest that zerumbone can exert its apoptotic activities by inhibiting the cytoplasmic proteins. It inhibits the IKKβ kinase that activates the NF-κB and also binds to the NF-κB complex in the TNF pathway. Blocking both proteins can lead to inhibition of cell proliferating proteins to be downregulated and possibly ultimate induction of apoptosis.


A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans.
These studies were undertaken to evaluate in humans the possible physiological role of prostaglandins of the E series (PGE) in modulating insulin release and to assess whether endogenous PGE synthesis may account for the biphasic pattern of insulin secretion. We used a square-wave glucose stimulation previously determined to give maximal biphasic insulin release. Infusion of lysine acetylsalicylate to block the synthesis of endogenous PGE increased by twofold total insulin response to glucose and also converted insulin release to a multiphasic pattern. The infusion of exogenous PGE1 (0.2 microgram X kg-1 X min-1) or PGE2 (10 micrograms/min) in addition to lysine acetylsalicylate restored the typical biphasic pattern of insulin release and also decreased total insulin release to values similar to those of control studies. Infusion of either PGE1 or PGE2 in the absence of lysine acetylsalicylate reset insulin secretion to a lower level without altering the kinetics of release. On the basis of these results, it is hypothesized that endogenous PGE released in response to glucose stimulation exert an inhibiting effect on insulin release that becomes biphasic in appearance.


Assessment of University Gynaecology Clinics Based on Quality Reports.
Introduction: Quality reporting was initially implemented to offer a better means of assessing hospitals and to provide patients with information to help them when choosing their hospital. Quality reports are published every 2 years and include parameters describing the hospital's structure and general infrastructure together with specific data on individual specialised departments or clinics. Method: This study investigated the 2010 quality reports of German university hospitals published online, focussing on the following data: number of inpatients treated by the hospital, focus of care provided by the unit/department, range of medical services and care provided by the unit/department, non-medical services provided by the unit/department, number of cases treated in the unit/department, ICD diagnoses, OPS procedures, number of outpatient procedures, day surgeries as defined by Section 115b SGB V, presence of an accident insurance consultant and number of staff employed. Results: University gynaecology clinics (UGCs) treat 10 % (range: 6-17 %) of all inpatients of their respective university hospital. There were no important differences in infrastructure between clinics. All UGCs offered full medical care and were specialist clinics for gynaecology (surgery, breast centres, genital cancer, urogynaecology, endoscopy), obstetrics (prenatal diagnostics, high-risk obstetrics); many were also specialist clinics for endocrinology and reproductive medicine. On average, each clinic employs 32 physicians (range: 16-78). Half of them (30-77 %) are specialists. Around 171 (117-289) inpatients are treated on average per physician. The most common ICD coded treatments were deliveries and treatment of infants. Gynaecological diagnoses are underrepresented. Summary: UGCs treat 10 % of all inpatients treated in university hospitals, making them important ports of entry for their respective university hospital. Around half of the physicians are specialists. Quality reports offer little information on the differences in competencies or medical specialties. The statutory quality reports are not useful for patients and referring physicians when choosing a clinic.


Pubertal course of persistently short children born small for gestational age (SGA) compared with idiopathic short children born appropriate for gestational age (AGA).
Few data are available on the pubertal development of children born small for gestational age (SGA) who fail to show catch-up growth. A longitudinal analysis compared the pubertal course of persistently short children born SGA compared to children with idiopathic short stature who were appropriate for gestational age (AGA). One hundred and twenty-eight short children (height SDS<-1.7), including 76 (31 boys) born SGA and 52 (22 boys) born AGA, were regularly followed from early childhood to completion of puberty. Puberty was attained at normal age (10.5-14 Years in boys, 9.5-13 Years in girls) for most children in both the SGA and AGA groups (boys, 80% and 77%; girls, 76% and 78% respectively). The duration of puberty was similar in the SGA and AGA groups. Menarche occurred at normal age range but was significantly earlier in the SGA girls (P<0.01 by ANOVA). Despite the similar total pubertal growth, the patterns of growth differed significantly: SGA group - accelerated growth and bone maturation rates from onset of puberty with peak height velocity at Tanner stages 2-3, followed by a decelerated growth rate and earlier fusion of the epiphyses; AGA group - steady progression of bone elongation and maturation throughout puberty (pubertal growth, P<0.05 in both sexes; bone maturation, P<0.001 in both sexes). Final height in the SGA group was compromised compared with their target height (P<0.001). Children born SGA have a normal pubertal course with a distinct pubertal growth pattern. This pattern may represent an altered regulation of their growth modalities.


Diradical character and nonlinear optical properties of buckyferrocenes: focusing on the use of suitably modified fullerene fragments.
The buckyferrocenes, synthesized through face-to-face fusion of ferrocene and fullerene fragments (C60Me10), are expected to enjoy the rich scientific heritage of ferrocene and fullerene with an extensively large π-conjugation network between the two Fe atoms [Y. Matsuo, K. Tahara and E. Nakamura, J. Am. Chem. Soc., 2006, 128, 7154]. However, the addition of pentamethyl groups at each end of the fullerene fragment breaks the π-conjugation path as well as metal-metal spin correlation between the two-ferrocene faces in a buckyferrocene. We found that the unblocking of π-conjugation from different positions in fullerene fragments have substantial effects on their topologies, spin densities, diradical characters as well as nonlinear optical (NLO) properties of these buckyferrocenes. We study the topological dependence of open-shell diradical character and second hyperpolarizability (γ), the third-order NLO properties at the molecular scale, in several buckyferrocenes. On the basis of their different diradical characters (yi), which are defined by the occupation number of the lowest unoccupied natural orbital (LUNO) + i (i = 0, 1,…), these buckyferrocenes are categorized into three groups, i.e., closed-shell (yi = 0), intermediate open-shell singlet (0 < yi < 1), and almost pure open-shell singlet (yi = 1) compounds. For example, we found that buckyferrocenes including (CpFe)2η(5)C60Me10 and (CpFe)2η(5)C70Me10 have closed-shell configurations. The buckyferrocenes (CpFe)2η(5)C60, (CpFe)2η(5)C70, (CpFe)2η(5)C70Me8, (CpFe)2η(5)C70Me4 and (CpFe)2η(5)C30 are intermediate open-shell singlet, while (CpFe)2η(5)C60Me4 and (CpFe)2η(5)C60Me8 are pure open-shell singlet complexes. Interestingly, the γzzzz amplitude of (CpFe)2η(5)C60, an open-shell intermediate diradical complex, is about 41 times and 13 times as large as those of its closed-shell ((CpFe)2η(5)C60Me10) and pure diradical ((CpFe)2η(5)C60Me8) counterparts, respectively. Similarly, the γzzzz amplitudes of (CpFe)2η(5)C70, (CpFe)2η(5)C70Me4, and (CpFe)2η(5)C70Me8 with intermediate diradical character are about 36, 17, and 9 times as large as that of their closed-shell (CpFe)2η(5)C70Me10 counterpart. The fact that larger γzzzz values are obtained for buckyferrocenes with intermediate diradical characters is in line with the "y-γ correlation" obtained from the valence configuration interaction (VCI) results for a two-site diradical model [M. Nakano, et al., Phys. Rev. Lett., 2007, 99, 033001] as well as for fullerene and graphene systems. The γzzzz density analysis shows that the large positive contributions originate from the large γzzzz density distributions on the upper- and lower-extended edges of the buckyferrocenes, between which significant spin polarizations appear within the spin-unrestricted DFT level of theory. These results demonstrate that such buckyferrocenes are potential candidates for a novel class of open-shell singlet NLO systems, where γzzzz values are modulated by tuning their diradical character through the use of suitably modified fullerene fragments.


Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre.
Mortality in pancreatic cancer has remained unchanged over the last 20-30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution. Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990-1999 and 2000-2009). Predictors of survival were analysed using univariate and multivariate analyses. Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990-1999 and 2000-2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990-1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome. Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.


Likelihood ratio-based integrated personal risk assessment of type 2 diabetes.
To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.


Cognitive performance at school age of very low birth weight infants with bronchopulmonary dysplasia.
The hypothesis was that bronchopulmonary dysplasia (BPD) adversely affects cognitive performance at school age. This prospective cohort study examined three groups of children at 8 to 10 years of age. Group 1 (n = 311) consisted of very low birth weight (VLBW) infants without BPD and Group 2 (n = 95) consisted of VLBW infants with BPD. Group 3 (n = 188) consisted of term infants without BPD. Regression analysis determined the effect of BPD on eight performance measures while controlling for possible confounding variables. Children in Group 3 had the best performance and children in Group 2 had the poorest performance on all measures. These differences were significant (p = .0001) for the Full Scale IQ, Performance IQ, and reading and math grades and ages. Children in Groups 3 and 1 performed better than children in Group 2 for the Verbal IQ (p = .0001) and the Developmental Test of Visual-Motor Integration (p = .0012), but for these two measures there was no significant difference between children in Groups 3 and 1. Thus, poorer performance was found in VLBW infants with a history of BPD.


Interactive evolution of camouflage.
This article presents an abstract computation model of the evolution of camouflage in nature. The 2D model uses evolved textures for prey, a background texture representing the environment, and a visual predator. A human observer, acting as the predator, is shown a cohort of 10 evolved textures overlaid on the background texture. The observer clicks on the five most conspicuous prey to remove ("eat") them. These lower-fitness textures are removed from the population and replaced with newly bred textures. Biological morphogenesis is represented in this model by procedural texture synthesis. Nested expressions of generators and operators form a texture description language. Natural evolution is represented by genetic programming (GP), a variant of the genetic algorithm. GP searches the space of texture description programs for those that appear least conspicuous to the predator.


The diagnosis and management of rheumatoid synovitis.
After establishing the diagnosis of rheumatoid arthritis one should determine the extent to which synovitic or structural lesions are responsible for the symptoms. Because structural lesions lack the potential for recovery, a plan should be laid out for their management, by either surgical correction or acceptance of the disability. In regard to the synovitis, one should determine whether it is likely to undergo a spontaneous remission. If a remission seems likely, the physician can manage the disease with a suppressive agent, usually salicylates. If a spontaneous remission seems unlikely and the patient's function is deteriorating, a clinical trial of either gold, hydroxychloroquin, or penicillamine is in order (in conjunction with a suppressive agent). If the first drug fails, one of the others should be tried next. There is no rationale for repeating a trial of one of these drugs if it has previously failed. If all three agents fail to produce a remission, the suppressive agent should be continued, and the physican serves as the patient's "friend" and frequently will be called upon to advise the patient about the need for reconstructive surgery.


Fern spore extracts can damage DNA.
The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has long been established. More recently, the carcinogenic effects of the spores of bracken have also been recognized. Both vegetative tissues and spores of bracken can induce adducts in DNA in animal tissues, but the possible genotoxic or carcinogenic effects of spores from fern species other than bracken are unknown. The single-cell gel electrophoresis ('comet') assay was used to investigate whether fern spores can cause DNA damage in vitro. Extracts of spores from six fern species were administered to cultured human premyeloid leukaemia (K562) cells. Spore extracts of five fern species: Anemia phyllitidis, Dicksonia antarctica, Pteridium aquilinum, Pteris vittata and Sadleria pallida, induced significantly more DNA strand breaks than those in the control groups. Only in one species, Osmunda regalis, was the effect no different from that in the control groups. Using extracts from A. phyllitidis and P. vittata, the extent of DNA damage was increased by increasing the original dose 10 times, whereas an experiment in which exposure times were varied suggested that the highest levels of strand breaks appear after 2 h exposure. Simultaneous incubation with human S9 liver enzyme mix ablated the damaging effect of the extracts. Our data show that fern spore extracts can cause DNA damage in human cells in vitro. Considering the strong correlation between DNA damage and carcinogenic events, the observations made in this report may well have some implications for human health.


Are We Ready for Mass Fatality Incidents? Preparedness of the US Mass Fatality Infrastructure.
To assess the preparedness of the US mass fatality infrastructure, we developed and tested metrics for 3 components of preparedness: organizational, operational, and resource sharing networks. In 2014, data were collected from 5 response sectors: medical examiners and coroners, the death care industry, health departments, faith-based organizations, and offices of emergency management. Scores were calculated within and across sectors and a weighted score was developed for the infrastructure. A total of 879 respondents reported highly variable organizational capabilities: 15% had responded to a mass fatality incident (MFI); 42% reported staff trained for an MFI, but only 27% for an MFI involving hazardous contaminants. Respondents estimated that 75% of their staff would be willing and able to respond, but only 53% if contaminants were involved. Most perceived their organization as somewhat prepared, but 13% indicated "not at all." Operational capability scores ranged from 33% (death care industry) to 77% (offices of emergency management). Network capability analysis found that only 42% of possible reciprocal relationships between resource-sharing partners were present. The cross-sector composite score was 51%; that is, half the key capabilities for preparedness were in place. The sectors in the US mass fatality infrastructure report suboptimal capability to respond. National leadership is needed to ensure sector-specific and infrastructure-wide preparedness for a large-scale MFI.


Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer.
Resistance to androgen receptor (AR) antagonists is a significant problem in the treatment of castration-resistant prostate cancers (CRPC). Identification of the mechanisms by which CRPCs evade androgen deprivation therapies (ADT) is critical to develop novel therapeutics. We uncovered that CRPCs rely on BRD4-HOXB13 epigenetic reprogramming for androgen-independent cell proliferation. Mechanistically, BRD4, a member of the BET bromodomain family, epigenetically promotes HOXB13 expression. Consistently, genetic disruption of HOXB13 or pharmacological suppression of its mRNA and protein expression by the novel dual-activity BET bromodomain-kinase inhibitors directly correlates with rapid induction of apoptosis, potent inhibition of tumor cell proliferation and cell migration, and suppression of CRPC growth. Integrative analysis revealed that the BRD4-HOXB13 transcriptome comprises a proliferative gene network implicated in cell-cycle progression, nucleotide metabolism, and chromatin assembly. Notably, although the core HOXB13 target genes responsive to BET inhibitors (HOTBIN10) are overexpressed in metastatic cases, in ADT-treated CRPC cell lines and patient-derived circulating tumor cells (CTC) they are insensitive to AR depletion or blockade. Among the HOTBIN10 genes, AURKB and MELK expression correlates with HOXB13 expression in CTCs of mCRPC patients who did not respond to abiraterone (ABR), suggesting that AURKB inhibitors could be used additionally against high-risk HOXB13-positive metastatic prostate cancers. Combined, our study demonstrates that BRD4-HOXB13-HOTBIN10 regulatory circuit maintains the malignant state of CRPCs and identifies a core proproliferative network driving ADT resistance that is targetable with potent dual-activity bromodomain-kinase inhibitors.


INCIDENTAL PAGET'S DISEASE DISGUISED AS BONE METASTASIS IN A PATIENT WITH ENDOMETRIUM CARCINOMA.
Paget's disease is a disorder of aging bone which occurs in the setting of accelarated bone remodelling. In the presented case we discuss the difficulties in the diagnosis of Paget's disease in a 77 year old patient with coexisting endometrium carcinoma. The patient was initially diagnosed with metastatic bone disease due to endometrium adenocarcinoma when she was admitted to oncology clinic with pelvic pain. Bone scintigraphy with Tc99 and (18)F fluorodeoxyglucose positron emission tomography/CT revealed an increased uptake on the bone lesions which were reported as metastatic bone involvement. Although the (18)F-FDG uptake was much higher than the levels that would generally be anticipated in a case with Paget's disease, high levels of bone turnover markers indicated further evaluation in the differential diagnosis and the definitive diagnosis of Paget's disease was established with the pathological evaluation of bone biopsy.


Pharmacologic reduction of the risk of aspiration.
Parameters for significant risk of aspiration have been defined as a gastric pH less than 2.5 and/or a volume greater than 25 ml. We investigated the effects of metoclopramide and cimetidine, alone and in combination, on the pH and volume of gastric contents of patients taking nothing by mouth before general anesthesia. We divided 40 young women having gynecologic surgery into four groups: control subjects (group 1), those given metoclopramide (group 2), those given cimetidine (group 3), and those given both drugs (group 4). Injections were given 45 to 90 minutes before induction of general anesthesia, and no other premedicant was allowed. When the mean pH and volume of gastric contents were measured, the patients given both drugs had a mean pH of 6.9 and a mean volume of 2.0 ml. The control group showed significant risk for aspiration in terms of both volume and pH. Use of metoclopramide alone reduced the risk related to volume, and cimetidine alone reduced the risk related to pH. The most striking effects were achieved by the combination of the two agents, which produced a relatively narrow range of "safe" pH and volume.


Health-related quality of life after revascularization for peripheral arterial occlusive disease: long-term follow-up.
This paper reports a study to measure quality of life, before and after revascularization, in patients with intermittent claudication and critical limb ischaemia from a long-term perspective. Patients with peripheral arterial occlusive disease have a number of problems which affect their quality of life and a successful revascularization results in immediate improvements in quality of life. However, knowledge of the durability of the improvements is sparse. Therefore, research on the outcomes of treatment and nursing care should investigate the long-term effects on quality of life and daily activities. A quasi-experimental longitudinal follow-up study was conducted with 80 patients with intermittent claudication and 62 with critical ischaemia. Assessment with the Nottingham Health Profile was made before revascularization and 6 months, 12 months and up to 4 years afterwards. The data were collected between 1995 and 2000. Quality of life was improved 6 and 12 months after revascularization in patients with intermittent claudication in energy, pain, emotional reactions and physical mobility, while those with critical limb ischaemia also had improvements in pain and sleep. The improvement in pain was particularly evident for both groups and remained significantly improved up to 4 years after revascularization. Patients with critical limb ischaemia, however, deteriorated significantly with regard to physical mobility between 12 months and 4 years. Being a woman and belonging to the critical ischaemia group was significantly associated with high total Nottingham Health Profile score. Thus, patients with intermittent claudication had more durable benefits from revascularization than those with critical limb ischaemia. However, both groups had less pain than at baseline after 4 years. The degree to which quality of life was durable over time seems to depend on the severity of the disease and gender. Patients with critical limb ischaemia were older, had more other diseases and a lower quality of life than patients with intermittent claudication, which confirmed that patients with critical limb ischaemia need more ongoing nursing support to maintain independence in daily life a long time after revascularization.


Vitamin D metabolites and risk of first clinical diagnosis of central nervous system demyelination.
Low 25-hydroxyvitamin D (25(OH)D) concentration is a recognised risk factor for multiple sclerosis (MS). Associations with vitamin D metabolites and vitamin D binding globulin (VDBG) have not been widely studied. We assessed the association between vitamin D metabolites (25(OH)D2, 25(OH)D3, c3-epimer 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) measured by liquid chromatography-tandem mass spectrometry assays, VDBG measured using a polyclonal immunoassay, and calculated free and bioavailable 25(OH)D, free 1,25(OH)2D3, and the 24,25(OH)2D3: total 25(OH)D and total 1,25(OH)2D: total 25(OH)D ratios with risk of a first clinical diagnosis of CNS demyelination (FCD) in an Australian case-control study (n = 196 cases, n = 241 controls, matched on age, sex and study region). Higher 25(OH)D (adjusted odds ratio (AOR) = 0.94 (95 % confidence interval (CI) 0.85-1.03) per 10 nmol/L increment) and 24,25(OH)2D3 (AOR = 0.81 (95 %CI 0.65-1.00) per 1 nmol/L increment) concentrations were associated with reduced FCD risk. Our results were compatible with no association for the other vitamin D metabolites, ratios, or VDBG with FCD risk. Thus, using standardised assays, and a comprehensive range of vitamin D metabolites, we confirmed the association of higher 25(OH)D and reduced FCD risk, and describe a similar effect for 24,25(OH)2D3; free or bioavailable 25(OH)D were not associated with FCD risk.


Cutaneous wound healing in space.
With the expected increase in extended-length space exploration missions and the establishment of permanent space stations, there is an increased chance of cutaneous injury occurring in astronauts due to trauma or unexpected emergency surgery. Will these wounds heal properly in space? This question remains unanswered. Several basic areas of the wound healing process need to be investigated through controlled scientific studies on spaceflights.


Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources.
During the recent Ebola crisis in West Africa, individual person-level details of disease onset, transmissions, and outcomes such as survival or death were reported in online news media. We set out to document disease transmission chains for Ebola, with the goal of generating a timely account that could be used for surveillance, mathematical modeling, and public health decision-making. By accessing public web pages only, such as locally produced newspapers and blogs, we created a transmission chain involving two Ebola clusters in West Africa that compared favorably with other published transmission chains, and derived parameters for a mathematical model of Ebola disease transmission that were not statistically different from those derived from published sources. We present a protocol for responsibly gleaning epidemiological facts, transmission model parameters, and useful details from affected communities using mostly indigenously produced sources. After comparing our transmission parameters to published parameters, we discuss additional benefits of our method, such as gaining practical information about the affected community, its infrastructure, politics, and culture. We also briefly compare our method to similar efforts that used mostly non-indigenous online sources to generate epidemiological information.


Coagulation Parameter Thresholds Associated with Non-Bleeding in the Eighth Hour of Adult Cardiac Surgical Post-Cardiotomy Extracorporeal Membrane Oxygenation.
Excessive bleeding and allogeneic transfusion during adult post-cardiotomy venoarterial extracorporeal membrane oxygenation (ECMO) are potentially harmful and expensive. Balancing the inhibition of clotting and distinguishing surgical from non-surgical bleeding in post-operative period is difficult. The sensitivity of coagulation tests including Thromboelastography(®) (TEG) to predict chest tube drainage in the early hours of ECMO was examined with the use of receiver-operating characteristics (ROC). The results are useful to incorporate in clinical evidence-based algorithms to guide management decisions. In the eighth hour of ECMO, 26 of the 53 adult patients (49%) studied were identified as non-bleeders (less than 2.0 mL/kg/h). All had experienced various types of cardiac surgical procedures. Fifty-two percent were female and the group was 54 ± 19 (mean ± 1 SD) years old. The coagulation parameter threshold with the maximum sensitivity and specificity to predict non-bleeding at 8 hours on ECMO was the kaolin plus heparinase TEG maximum amplitude (KH-TEG MA) at a significant ROC threshold (t) > 50 mm. The activated partial thromboplastin time (aPTT) t < 49 seconds, KH-TEG alpha-angle t > 51°, and the kaolin activated clotting time (ACT) t < 148 seconds were sensitive predictors of non-bleeders. The whole-blood KH-TEG MA was superior to the plasma-based aPTT or International Normalization Ratio (INR) to predict bleeding in the eighth hour of ECMO. Using coagulation laboratory thresholds that predict non-bleeding can begin a process of identifying patients earlier that are likely to bleed. Awareness of these parameter thresholds may improve care through patient protection from unnecessary transfusion and prolonging the life of the ECMO circuit. An algorithm incorporating the ROC thresholds was created to help recognize surgical bleeding to minimize unnecessary transfusions.


Program for Integration and Rapid Analysis of Mass Isotopomer Distributions (PIRAMID).
The analysis of stable isotope labeling experiments requires accurate, efficient, and reproducible quantification of mass isotopomer distributions (MIDs), which is not a core feature of general-purpose metabolomics software tools that are optimized to quantify metabolite abundance. Here, we present PIRAMID (Program for Integration and Rapid Analysis of Mass Isotopomer Distributions), a MATLAB-based tool that addresses this need by offering a user-friendly, graphical user interface-driven program to automate the extraction of isotopic information from mass spectrometry (MS) datasets. This tool can simultaneously extract ion chromatograms for various metabolites from multiple data files in common vendor-agnostic file formats, locate chromatographic peaks based on a targeted list of characteristic ions and retention times, and integrate MIDs for each target ion. These MIDs can be corrected for natural isotopic background based on the user-defined molecular formula of each ion. PIRAMID offers support for datasets acquired from low- or high-resolution MS, and single (MS) or tandem (MS/MS) instruments. It also enables the analysis of single or dual labeling experiments using a variety of isotopes (i.e. 2H, 13C, 15N, 18O, 34S). MATLAB p-code files are freely available for non-commercial use and can be downloaded from https://mfa.vueinnovations.com/. Commercial licenses are also available. All the data presented in this publication are available under the "Help_menu" folder of the PIRAMID software.


Application of an analytic model to early readmission rates within the Department of Veterans Affairs.
Adverse outcome rates are increasingly used as yardsticks for the quality of hospital care. However, the validity of many outcome studies has been undermined by the application of one outcome to all patients in large, diagnostically diverse populations, many of which lack evidence of a link between antecedent process of care and the rate of the outcome, the underlying assumption of the analysis. To address this analytic problem, the authors developed a model that improves the ability to identify quality problems because it selects diseases for which there are processes of care known to affect the outcome of interest. Thus, for these diseases, the outcome is most likely to be causally related to the antecedent care. In this study of hospital readmissions, risk-adjusted models were created for 17 disease categories with strong links between process and outcome. Using these models, we identified outlier hospitals. The authors hypothesized that if the model improved on identifying hospitals with quality of care problems, then outlier status would not be random. That is, hospitals found to have extreme rates in one year would be more likely to have extreme rates in subsequent years, and hospitals with extreme rates in one condition would be more likely to have extreme rates in related disease categories. It was hypothesized further that the correlation of outlier status across time and across diseases would be stronger in the 17 disease categories selected by the model than in 10 comparison disease categories with weak links between process and outcome. The findings support all these hypotheses. Although the present study shows that the model selects disease-outcome pairs where hospital outlier status is not random, the causal factors leading to outlier status could include (1) systematic unmeasured patient variation, (2) practice pattern variation that, although stable with time, is not indicative of substandard care, or (3) true quality-of-care problems. Primary data collection must be done to determine which of these three factors is most causally related to hospital outlier status.


Incidence and Detection of Meniscal Ramp Lesions on Magnetic Resonance Imaging in Patients With Anterior Cruciate Ligament Reconstruction.
Meniscal ramp lesions have been reported to be present in 9% to 17% of patients undergoing anterior cruciate ligament (ACL) reconstruction. Detection at the time of arthroscopy can be accomplished based on clinical suspicion and careful evaluation. Preoperative assessment via magnetic resonance imaging (MRI) has been reported to have a low sensitivity in identifying meniscal ramp lesions. To investigate the incidence of meniscal ramp lesions in patients with ACL tears and the sensitivity of preoperative MRI for the detection of ramp lesions. Case series; Level of evidence, 4. All patients who underwent ACL reconstruction by a single surgeon between 2010 and 2016 were included in this study, and patients with medial meniscal ramp lesions found at the time of arthroscopy were identified. The sensitivity of MRI compared with the gold standard of arthroscopic evaluation was determined by review of the preoperative MRI musculoskeletal radiologist report, mimicking the clinical scenario. The incidence was calculated based on arthroscopic findings, and the potential secondary signs of meniscal ramp tears were evaluated on MRI. In a consecutive series of 301 ACL reconstructions, 50 patients (33 male, 17 female) with a mean age of 29.6 years (range, 14-61 years) were diagnosed with a medial meniscal ramp lesion at arthroscopic evaluation (16.6% incidence). The sensitivity of MRI for ramp lesions was 48% based on the preoperative MRI report. A secondary finding of a posteromedial tibial bone bruise was identified on preoperative MRI in 36 of the 50 patients with ramp lesions in a retrospective MRI review by 2 orthopaedic surgeons. Medial meniscal ramp lesions were present in approximately 17% of 301 patients undergoing ACL reconstruction, and less than one-half were diagnosed on the preoperative MRI. A posteromedial tibial bone bruise was found to be a secondary sign of a ramp lesion in 72% of patients. Increased awareness of this potentially combined injury pattern is necessary, and careful intraoperative evaluation is required to identify all meniscal ramp tears.


Psychometric Validation of the 10-item Connor-Davidson Resilience Scale.
Resilience is the personality trait of having positive dispositions which enable individuals to cope with stressful situations. Hence, a reliable resilience scale can provide useful information on understanding and treating individuals suffering from stress and trauma. The 10-item Connor-Davidson Resiliance Scale (CD-RISC-10) is a candidate scale. However, very little psychometric research has been conducted on this scale and, moreover, psychometric analyses to date have not been conclusive. To attain further evidence of the scale's psychometric properties, we tested the CD-RISC-10 on 288 adult Education major students at an Australian University using both traditional (factor analyses) and modern (Rasch) measurement approaches. Factor analyses indicated good psychometric functioning of the scale. However, Rasch modelling revealed evidence of item misfit and multiple dimensions. Optimal performance was achieved after the removal of two misfitting items indicating a well-functioning 8-item scale.


Donor site morbidity in two different approaches to anterior iliac crest bone harvesting.
Bone grafting is a surgical technique for the reconstruction of the atrophic edentulous maxilla prior to treatment with endosseous implants. The anterior iliac crest is a commonly used donor site. The aim of this study was to evaluate the donor site morbidity and complications when harvesting corticocancellous bone from the medial table of the anterior iliac crest and compare this with results when bone was harvested from the lateral and superior table of the anterior iliac crest. In addition, the outcome of the oral rehabilitation was evaluated by means of a quality-of-life questionnaire. The study was composed of 70 consecutively treated patients with a mean age of 56 years. The patients were retrospectively evaluated with regard to postoperative donor site morbidity and complications at the donor site. For the donor site morbidity, 74% of the patients were free of pain within 3 weeks, whereas 26% of the patients had a prolonged period of pain lasting from a few weeks to several months. For 11% of the patients, there was still some pain or discomfort 2 years after the grafting surgery. For gait disturbance the figures were similar: 79% had no problems after 3 weeks. For the eight patients who still had some pain after 2 years, which was considered permanent, three also had gait disturbance. There was a total of three major complications (4%), one iliac wing fracture and two neurologic injuries. When harvesting a large amount of unicortical corticocancellous bone blocks from the the superolateral site of the iliac crest with a "peel off" technique, morbidity and complication rates do not differ significantly compared with those of the traditional anterior medial approach. Oral rehabilitation with maxillary reconstruction with bone grafts from the iliac crest and endosseous implants significantly improved oral function, facial appearance, and recreation/social activities and resulted in an overall improvement in quality of life in formerly edentulous patients.


[A mathematical model of the functional state of the hemopoietic and erythropoietic system].
Proposed is a mathematical model of the functional state of the hemopoietic and erythropoietic systems in microgravity or long-term bed rest built on the principle of the minimal energy demand. Parameters of hematocrit, blood volume and minute blood volume in microgravity or long-term bed rest were determined. Results of model testing are in good agreement with the data about functioning of these systems in cosmonauts.


Palmar and plantar pustulosis elicited by Candida antigen.
Intracutaneous injection of Candida albicans was done on the forearm of 30 patients with palmar and plantar pustulosis. This induced an aggravation of pustular eruptions on the palms and soles in 11 (37%) of the 30 patients. The aggravation occurred only in those patients who had a positive delayed skin reaction to the Candida antigen. It is suggested that a delayed hypersensitivity inflammatory reaction somewhere in the body is attended with an aggravation of palmar plantar pustulosis.


Allopregnanolone targets nucleoprotein as a novel influenza virus inhibitor.
Influenza A virus (IAV) poses a global public health concern and remains an imminent threat to human health. Emerging antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new therapeutic entities against IAV. Allopregnanolone (ALLO) is a natural product that has been approved as an antidepressant drug. In the present study, we repurposed ALLO as a novel inhibitor against IAVs. Mechanistic studies demonstrated that ALLO inhibited virus replication by interfering with the nucleus translocation of viral nucleoprotein (NP). In addition, ALLO showed significant synergistic activity with compound 16, a hemagglutinin inhibitor of IAVs. In summary, we have identified ALLO as a novel influenza virus inhibitor targeting NP, providing a promising candidate that deserves further investigation as a useful anti-influenza strategy in the future.


On-demand dark soliton train manipulation in a spinor polariton condensate.
We theoretically demonstrate the generation of dark soliton trains in a one-dimensional exciton-polariton condensate within experimentally accessible schemes. In particular, we show that the frequency of the train can be finely tuned fully optically or electrically to provide a stable and efficient output signal modulation. Taking the polarization of the condensate into account, we elucidate the possibility of forming on-demand half-soliton trains.


Regional variation in nonmedical factors affecting family physicians' decisions about referral for consultation.
To determine whether there is regional variation in environmental (non-medical) factors affecting referral decisions of family physicians (FPs). Cross-sectional interview survey. Nova Scotia. A random sample of 125 FPs grouped into 1 of 5 functionally defined geographic regions of Nova Scotia (25 in each group). Groupings were based on access to general hospital beds through active staff hospital appointments or to specialist consultants in the community, or both. Participants were personally interviewed on site. No physician refused an interview. In 9 cases the physician indicated that he or she did not fit the profile of the assigned group; the physician was excluded from the study and the next doctor on the list was substituted. The questionnaire was designed to test several hypotheses about factors known to potentially influence decisions about referral. Geographic differences in factors affecting referral and in decisions about 5 hypothetical cases were assessed with the use of significance tests for proportions that were sensitive to specific orders across groups. Three factors affecting referral showed unequivocal variation across the 5 groups. Access to hospital facilities and remoteness from specialist care, leading to local styles of practice or treatment policies, and the FP's relationship with specialist consultants appeared to be important nonmedical factors affecting referral decisions. For similar case scenarios the physicians living in rural areas would refer only half as often overall as those living in urban areas with tertiary care hospitals; for some cases, such as a severe asthma attack, the difference was more than 7-fold. Significant differences in nonmedical factors affecting referral, and in referral decisions about hypothetical cases, were found between the groups of FPs. Differences in access to resources, creating local styles of practice, appeared to explain most of the variation. The results may account for previously observed differences in actual rates of referral for these particular groups.


Data on optimization of expression and purification of AIMP2-DX2 protein in Escherichia coli.
AIMP2-DX2 is a splicing variant of AIMP2 protein which has been implicated in human lung cancer and chemoresistance of ovarian cancer (J.W. Choi, D.G. Kim, A.E. Lee, H.R. Kim, J.Y. Lee, N.H. Kwon, et al., 2011; J.W. Choi, J.W. Lee, J.K. Kim, H.K. Jeon, J.J. Choi, D.G. Kim, et al., 2012) [1,2]. We have shown, here, the data for the expression of AIMP2-DX2 protein in Escherichia coli and optimization of the critical steps in purification of AIMP2-DX2. The data described here has been successfully used to get a maximum yield of highly pure AIMP2-DX2 for subsequent characterization of its biophysical property in: "Purification and biophysical characterization of the AIMP2-DX2 protein" (R. Jha, H.Y. Cho, A. Ul Mushtaq, K. Lee, D.G. Kim, S. Kim, et al., 2017) [3].


Factors related to childhood suicides: analysis of the Queensland Child Death Register.
Suicide among children under the age of 15 years is a leading cause of death. The aim of the current study is to identify demographic, psychosocial, and psychiatric factors associated with child suicides. Using external causes of deaths recorded in the Queensland Child Death Register, a case-control study design was applied. Cases were suicides of children (10-14 years) and adolescents (15-17 years); controls were other external causes of death in the same age band. Between 2004 and 2012, 149 suicides were recorded: 34 of children aged 10-14 years and 115 of adolescents aged 15-17 years. The gender asymmetry was less evident in child suicides and suicides were significantly more prevalent in indigenous children. Children residing in remote areas were significantly more likely to die by suicide than other external causes compared with children in metropolitan areas. Types of precipitating events differed between children and adolescents, with children more likely to experience family problems. Disorders usually diagnosed during infancy, childhood, and adolescence (e.g., ADHD) were significantly more common among children compared with adolescents who died by suicide. Psychosocial and environmental aspects of children, in addition to mental health and behavioral difficulties, are important in the understanding of suicide in this age group and in the development of targeted suicide prevention.


E7080 suppresses hematogenous multiple organ metastases of lung cancer cells with nonmutated epidermal growth factor receptor.
While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors improve the prognosis of patients with EGFR mutant lung cancer, the prognosis of patients with nonmutant EGFR lung cancer, especially those with metastases, is still extremely poor. We have assessed the therapeutic efficacy of E7080, an orally available inhibitor of multiple tyrosine kinases including VEGF receptor 2 (VEGFR-2) and VEGFR-3, in experimental multiple organ metastasis of lung cancer cell lines without EGFR mutations. E7080 markedly inhibited the in vitro proliferation of VEGF-stimulated microvascular endothelial cells. Intravenous inoculation into natural killer cell-depleted severe combined immunodeficient mice of the small cell lung cancer cell lines H1048 (producing low amounts of VEGF) and SBC-5 (producing intermediate amounts of VEGF) resulted in hematogenous metastases into multiple organs, including the liver, lungs, kidneys, and bones, whereas intravenous inoculation of PC14PE6, a non-small cell lung cancer cell line producing high amounts of VEGF, resulted in lung metastases followed by massive pleural effusion. Daily treatment with E7080 started after the establishment of micrometastases significantly reduced the number of large (>2 mm) metastatic nodules and the amount of pleural effusion, and prolonged mouse survival. Histologically, E7080 treatment reduced the numbers of endothelial and lymph endothelial cells and proliferating tumor cells and increased the number of apoptotic cells in metastatic nodules. These results suggest that E7080 has antiangiogenic and antilymphangiogenic activity and may be of potential therapeutic value in patients with nonmutant EGFR lung cancer and multiple organ metastases.


Alberta Stroke Program Early CT Score Infarct Location Predicts Outcome Following M2 Occlusion.
Although it is generally thought that patients with distal middle cerebral artery (M2) occlusion have a favorable outcome, it has previously been demonstrated that a substantial minority will have a poor outcome by 90 days. We sought to determine whether assessing the Alberta Stroke Program Early CT Score (ASPECTS) infarct location allows for identifying patients at risk for a poor 90-day outcome. We retrospectively analyzed patients with isolated acute M2 occlusion admitted to a single academic center between January 2010 and August 2012. Infarct regions were defined according to ASPECTS system on the initial head computed tomography. Discriminant function analysis was used to define specific ASPECTS regions that are predictive of the 90-day functional outcome as defined as a modified Rankin Scale score of 3-6. In addition, logistic regression was used to model the relationship between each individual ASPECT region with poor outcome; for evaluation and comparison, odds ratios, c-statistics, and Akaike information criterion values were estimated for each region. Ninety patients with isolated M2 were included in the final analysis. ASPECTS score ≤6 predicted poor outcome in this cohort (sensitivity = 0.591, specificity = 0.838, p < 0.001). Using multiple approaches, we found that infarction in ASPECTS regions M3 and M6 were strongly associated with poor functional status by 90 days. Infarction in ASPECTS regions M3 and M6 are key predictors of functional outcome following isolated distal M2 occlusion. These findings will be helpful in stratifying outcomes if validated in future studies.


Age-related eye diseases: an emerging challenge for public health professionals.
In April 2004, The Eye Disease Prevalence Research Group published a series of articles that included age-specific estimates for the prevalence of low vision and blindness in whites, African Americans, and Hispanics living in the United States. Also included were age-, sex-, and ethnic-specific incidences of the following age-related eye diseases: diabetic retinopathy, macular degeneration, cataracts, and glaucoma. We reviewed the group's series of articles and highlighted key findings on the overall prevalence of and risk factors for age-related eye diseases, as well as opportunities to preserve and restore vision. We examined publications that show the public health impact of age-related eye diseases and the importance of projected increases in prevalence of low vision and blindness. Approximately 1 in 28 Americans aged older than 40 years is affected by low vision or blindness. Among community-dwelling adults, the prevalence of low vision and blindness increases dramatically with age in all racial and ethnic groups. Whites have higher rates of macular degeneration than African Americans, but glaucoma is more common among older African Americans. Between 2000 and 2020, the prevalence of blindness is expected to double. Age-related eye diseases are costly to treat, threaten the ability of older adults to live independently, and increase the risk for accidents and falls. To prevent vision loss and support rehabilitative services for people with low vision, it is imperative for the public health community to address the issue through surveillance, public education, and coordination of screening, examination, and treatment.


[Clinical observations and angiographic findings before and after aortocoronary benous bypass grafting (author's transl)].
37 patients (mean age 51 +/- 8 years) were investigated clinically, mechanocardiographically and angiocardiographically before and 336 +/- 166 days after implantation of an aortocoronary vein graft. The bypass patency rate was 78%. Postoperatively 57% of the patients were free of symptoms, 35% were improved and 8% unimproved or worse. The postoperative incidence of angina pectoris during exercise testing was significantly lower in the groups with an improved vascularization-index, open vein grafts and a lack of preoperative myocardial infarction. For separating the patients only the vascularization-index and the bypass patency seem to be of value.


Cumulative risk of cancer detection in breast cancer screening by protocol strategy.
There is little information on the individual risk of screen-detected cancer in women over successive participations. This study aimed to estimate the 10-year cumulative breast cancer detection risk (ductal carcinoma in situ and invasive carcinoma) in a population-based breast cancer screening program according to distinct protocol strategies. A further aim was to determine which strategies maximized the cancer detection risk and how this risk was affected by the radiologic protocol variables. Data were drawn from a retrospective cohort of women from nine population-based screening programs in Spain from 1990 to 2006. We used logistic regression with discrete intervals to estimate the cumulative detection risk at 10 years of follow-up according to radiologic variables and protocol strategies. In women starting screening at the age of 45-59 years, the cumulative risk of screen-detected cancer at 10 years ranged from 11.11 to 16.71 per 1,000 participants according to the protocol strategy. The cumulative detection risk for overall cancer and invasive cancer was the highest with strategies using digital mammography, double reading, and two projections (16.71 and 12.07 ‰, respectively). For ductal carcinoma in situ, cumulative detection risk was the highest with strategies using screen-film, double reading, and two projections (2.32 ‰). The risk was the lowest with strategies using screen-film mammography, single reading, and two projections. This study found that at least eleven cancers are detected per 1,000 women screened in the first 10 years of follow-up. Enhanced knowledge of the variability in cumulative risk of screen-detected cancer could improve protocol strategies.


Bovine tuberculosis at a cattle-small ruminant-human interface in Meskan, Gurage region, Central Ethiopia.
Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. The aim of this study was to assess BTB prevalence at an intensive contact interface in Meskan Woreda (district) in cattle, small ruminants and suspected TB-lymphadenitis (TBLN) human patients. The comparative intradermal test (CIDT) was carried out for all animals involved in the cross-sectional study and results interpreted using a > 4 mm and a > 2 mm cut-off. One PPD positive goat was slaughtered and lymph nodes subjected to culture and molecular typing. In the same villages, people with lymphadenitis were subjected to clinical examination. Fine needle aspirates (FNA) were taken from suspected TBLN and analyzed by smear microscopy and molecular typing. A total of 1214 cattle and 406 small ruminants were tested for BTB. In cattle, overall individual prevalence (> 2 mm cut-off) was 6.8% (CI: 5.4-8.5%) with 100% herd prevalence. Only three small ruminants (2 sheep and 1 goat) were reactors. The overall individual prevalence in small ruminants (> 2 mm cut-off) was 0.4% (CI: 0.03-5.1%) with 25% herd prevalence. Cattle from owners with PPD positive small ruminants were all PPD negative. 83% of the owners kept their sheep and goats inside their house at night and 5% drank regularly goat milk.FNAs were taken from 33 TBLN suspected cases out of a total of 127 screened individuals with lymph node swellings. Based on cytology results, 12 were confirmed TBLN cases. Nine out of 33 cultures were AFB positive. Culture positive samples were subjected to molecular typing and they all yielded M. tuberculosis. M. tuberculosis was also isolated from the goat that was slaughtered. This study highlighted a low BTB prevalence in sheep and goats despite intensive contact with cattle reactors. TBLN in humans was caused entirely by M. tuberculosis, the human pathogen. M. tuberculosis seems to circulate also in livestock but their role at the interface is unknown.


Modification of telomeric DNA in Trypanosoma brucei; a role in antigenic variation?
Expression of surface antigen genes in Trypanosoma brucei occurs at expression sites located near telomeres. Since only one antigen is produced at a time, a mechanism must exist to prevent the simultaneous activity of multiple expression sites. Here we report that PstI and PvuII restriction sites in silent telomeric antigen genes are partially uncleavable , presumably as a consequence of DNA modification. The modification, which is absent in transcribed genes but returns after gene inactivation, may be specific for telomeric DNA because (1) it is not detected in non-telomeric genes; (2) modification is highest close to the telomere; (3) the level of modification in a telomeric gene is influenced by the size of the telomeric DNA segment downstream. Whether telomere modification is cause or consequence of antigen gene switch-off remains to be determined.


Cutting edge: selective expression of inhibitory or activating killer cell Ig-like receptors in circulating CD4+ T lymphocytes.
Apart from NK cells, TCRgammadelta and CD8+ T cells, killer cell Ig-like receptor (KIR) expression was described on a minor subset of CD4+ T cells. However, their functions remain to be elucidated in this latter lymphocyte population. We demonstrated that KIR2DL2/L3 (CD158b) and KIR2DS2 (CD158j) transcripts were synthesized by sorted CD4+CD158b/j+ T cells obtained from healthy individuals. In contrast, we observed that only the inhibitory or activating receptor was expressed at the cell surface according to the donor tested. In CD158b-expressing cells, KIR triggering leads to an inhibition of the CD3-induced cell proliferation and Erk activation, and the receptor exhibits an activation-dependent tyrosine phosphorylation and association with the Src homology 2-containing phosphatase 1. In CD158j-positive cells, KIR-engagement results in an enhanced CD3-mediated cell growth and Erk phosphorylation. Our results suggested that, in contrast to NK cells, the functions of KIR in CD4+ T lymphocytes might derive from a selective expression of their activating or inhibiting forms.


Salivary protein profiles and sensitivity to the bitter taste of caffeine.
The interindividual variation in the sensitivity to bitterness is attributed in part to genetic polymorphism at the taste receptor level, but other factors, such as saliva composition, might be involved. In order to investigate this, 2 groups of subjects (hyposensitive, hypersensitive) were selected from 29 healthy male volunteers based on their detection thresholds for caffeine, and their salivary proteome composition was compared. Abundance of 26 of the 255 spots detected on saliva electrophoretic patterns was significantly different between hypo- and hypersensitive subjects. Saliva of hypersensitive subjects contained higher levels of amylase fragments, immunoglobulins, and serum albumin and/or serum albumin fragments. It also contained lower levels of cystatin SN, an inhibitor of protease. The results suggest that proteolysis occurring within the oral cavity is an important perireceptor factor associated to the sensitivity to the bitter taste of caffeine.


Distant homologs of anti-apoptotic factor HAX1 encode parvalbumin-like calcium binding proteins.
Apoptosis is a highly ordered and orchestrated multiphase process controlled by the numerous cellular and extra-cellular signals, which executes the programmed cell death via release of cytochrome c alterations in calcium signaling, caspase-dependent limited proteolysis and DNA fragmentation. Besides the general modifiers of apoptosis, several tissue-specific regulators of this process were identified including HAX1 (HS-1 associated protein X-1) - an anti-apoptotic factor active in myeloid cells. Although HAX1 was the subject of various experimental studies, the mechanisms of its action and a functional link connected with the regulation of apoptosis still remains highly speculative. Here we provide the data which suggests that HAX1 may act as a regulator or as a sensor of calcium. On the basis of iterative similarity searches, we identified a set of distant homologs of HAX1 in insects. The applied fold recognition protocol gives us strong evidence that the distant insects' homologs of HAX1 are novel parvalbumin-like calcium binding proteins. Although the whole three EF-hands fold is not preserved in vertebrate our analysis suggests that there is an existence of a potential single EF-hand calcium binding site in HAX1. The molecular mechanism of its action remains to be identified, but the risen hypothesis easily translates into previously reported lines of various data on the HAX1 biology as well as, provides us a direct link to the regulation of apoptosis. Moreover, we also report that other family of myeloid specific apoptosis regulators - myeloid leukemia factors (MLF1, MLF2) share the homologous C-terminal domain and taxonomic distribution with HAX1. Performed structural and active sites analyses gave new insights into mechanisms of HAX1 and MLF families in apoptosis process and suggested possible role of HAX1 in calcium-binding, still the analyses require further experimental verification.


Soluble FAS in the prediction of benefit from cetuximab and irinotecan for patients with advanced colorectal cancer.
The FAS/FASL system, comprising membrane-bound (mFAS and mFASL) and soluble forms (sFAS and sFASL), has been related to apoptosis driven by chemotherapy administration. In vitro experiments show chemotherapy upregulating membrane-bound forms, leading to an increase of receptor availability (at 24-72 h) and favoring apoptosis. The regulatory effect of chemotherapy on sFAS in patients has never been explored prospectively in advanced colorectal cancer (ACRC). We performed a pharmacodynamic study to address sFAS/sFASL variation. A prospective phase II translational multicenter study was designed to evaluate progression-free rate (PFR) in patients with ACRC treated with irinotecan and cetuximab in third-line therapy. The effect of sFAS was studied in vitro in colorectal cancer cell lines. Our results showed that statistically significant changes were observed in sFAS at 24-72 h compared to baseline levels in the pharmacodynamic study. Of the 93 patients enrolled in the prospective study in third-line therapy with cetuximab-irinotecan, 85 were evaluated for sFAS/sFASL changes at 48 h. There was no difference in PFR at 4 months between patients with sFAS and sFASL changes. In vitro analysis showed that although LoVo cell lines were sensitive to oxaliplatin and fluorouracil due to modulation of sFAS and FAS, HT29 lines were not. In summary, chemotherapy regulates FAS soluble fractions in vitro and in vivo, but does not predict PFR in ACRC patients undergoing third-line therapy with the combination of cetuximab and irinotecan.


A custom-made two-photon microscope and deconvolution system.
We describe in detail a custom-built two-photon microscope based on a modified confocal scanhead (Olympus Fluoview) and mode-locked Ti:sapphire laser (Coherent Mira 900). This system has internal detectors as well as external whole-field detection and an electrooptical modulator for blanking the beam on flyback and effecting fast changes in excitation intensity. This microscope can be used in deep, scattering samples for quantitative measurements with a wide range of fluorophores (GFP, fura, calcium green, calcium orange, fluo-3, DiI, DiO, fluorescein, rhodamine), for fluorescent photobleaching recovery and for uncaging. Images obtained with this system can be deconvolved with the Estimation Maximization algorithm using the program XCOSM (freeware available at: http://www.ibc.wustl.edu/bcl/ xcosm/).


Facile and Scalable Synthesis of Zn3V2O7(OH)2·2H2O Microflowers as a High-Performance Anode for Lithium-Ion Batteries.
The employment of nanomaterials and nanotechnologies has been widely acknowledged as an effective strategy to enhance the electrochemical performance of lithium-ion batteries (LIBs). However, how to produce nanomaterials effectively on a large scale remains a challenge. Here, the highly crystallized Zn3V2O7(OH)2·2H2O is synthesized through a simple liquid phase method at room temperature in a large scale, which is easily realized in industry. Through suppressing the reaction dynamics with ethylene glycol, a uniform morphology of microflowers is obtained. Owing to the multiple reaction mechanisms (insertion, conversion, and alloying) during Li insertion/extraction, the prepared electrode delivers a remarkable specific capacity of 1287 mA h g-1 at 0.2 A g-1 after 120 cycles. In addition, a high capacity of 298 mA h g-1 can be obtained at 5 A g-1 after 1400 cycles. The excellent electrochemical performance can be attributed to the high crystallinity and large specific surface area of active materials. The smaller particles after cycling could facilitate the lithium-ion transport and provide more reaction sites. The facile and scalable synthesis process and excellent electrochemical performance make this material a highly promising anode for the commercial LIBs.


Diet alters species recognition in juvenile toads.
Whether environmental effects during juvenile development can alter the ontogeny of adult mating behaviour remains largely unexplored. We evaluated the effect of diet on the early expression of conspecific recognition in spadefoot toads, Spea bombifrons. We found that juvenile toads display phonotaxis behaviour six weeks post-metamorphosis. However, preference for conspecifics versus heterospecifics emerged later and was diet dependent. Thus, the environment can affect the early development of species recognition in a way that might alter adult behaviour. Evaluating such effects is important for understanding variation in hybridization between species and the nature of species boundaries.


The impact of Synergy Model on nurses' performance and the satisfaction of patients with acute coronary syndrome.
Despite many progresses in the improvement of care status and the management of acute coronary syndrome, cares quality is far from the desirable conditions. Today, due to the great emphasis on resources management, costs control, the effectiveness of patient care, improving quality and responsibility, the good patient care is necessary. Two dimensions are referred for improving the quality: process (standard- based and safe services) and resultant (client satisfaction). The present study, aimed at determining the impact of Synergy Model on nurses' performance and the satisfaction of the patients with acute coronary syndrome. In a quasi- experimental study in a two-group and two-step form, a sample of 22 nurses and 64 patients with acute coronary syndrome in cardiac intensive care units of some university hospitals in 2010-2011 were recruited. Synergy Model was explained and carried out for the studied groups in a workshop and its impact on nurses performance in different areas and patients' satisfaction was examined by using two checklists: examining the nurses' performance quality and examining the patients satisfaction. Differences between the mean scores of the nurses in communicative, supportive, care and educational domains and total performance were statistically significant before and after the intervention (p < 0.001). However, in therapeutic domain, changes were not significant. There was a statistically significant difference between the average satisfaction score of the two groups (p < 0.001). Applying Synergy Model as a basis for receiving nursing cares was effective in increasing patient satisfaction and in the performance of nurses of cardiac intensive care units.


A clinical study on the tip localization of peripherally inserted central catheter (PICC) guided by intracavitary electrocardiography in newborns: a randomised trial.
The present study aimed to investigate the P-wave changes in intracavitary electrocardiography (IC-ECG) during catheterization with a peripherally inserted central catheter (PICC) in order to provide guidance for the accurate localization of the tip of the PICC. A total of 106 newborns who needed a PICC were randomly divided into two groups-a study group and a control group-using a random number table, with 53 cases in each group. In the study group, the ECG monitor was connected after the successful puncture and insertion of the PICC into the right sternoclavicular joint, and the position of the catheter tip was determined according to the P-wave changes on the IC-ECG. Localization X-rays were taken at the same time. In the control group, after the successful routine puncture and insertion of the PICC into the location to a predetermined length, localization X-rays were taken. The accuracy, procedure duration, and cost of the two localization methods were evaluated. The accuracy of the localization in the study group was 92.5%, but the difference was not significant when compared with the control group (P>0.05). The duration of the procedure in the study group was 5.12±1.57 minutes, and the cost was 7.12±0.56 yuan, both of which were significantly different when compared with the control group (P<0.05). P-wave changes during IC-ECG have high accuracy in determining the location of the tip of the PICC. It is also a simple method and has certain clinical application value. Chinese Clinical Trial Registry (number: ChiCTR2100047660).


Emergency department evaluation of a rapid assay for detection of cocaine metabolites in urine specimens.
We evaluated the Abuscreen ONTRAK assay for cocaine metabolites, a rapid immunoassay for the detection of cocaine metabolites in a pediatric emergency department (ED) setting. The ONTRAK uses a cutoff point of 300 micrograms/L for benzoylecgonine (BEC), cocaine's major urinary metabolite. One hundred and thirty-two urine specimens obtained from infants, children, and adolescents whose clinical findings warranted toxicology screening were evaluated. The ONTRAK identified all 15 specimens with BEC values of 300 micrograms/L, but did not detect seven additional specimens positive for cocaine metabolites at concentrations less than 300 micrograms/L. One third of the positive specimens for cocaine metabolite identified by fluorescent polarization immunoassay (FPIA), cutoff point set at 80 micrograms/L, and confirmed by gas chromatography/mass spectrometry (GUMS), cutoff point 50 micrograms/L, were not detected by the ONTRAK. These false negative specimens were seen exclusively in young children, whose concentration of cocaine metabolite was less than the ONTRAK's cutoff value. The test was sensitive to drug concentration at or around the stated cutoff values. The ONTRAK test for cocaine metabolites, although both a sensitive and specific screening test for adolescents who smoke or snort cocaine, lacks the sensitivity to be a useful screening too[ for detecting cocaine metabolites in young children. Limitations of currently performed toxicology screening tests (ie, stated cutoff levels) may cause emergency physicians to miss most young children whose symptoms may he related to cocaine exposure.


Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention.
Aims It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population. Methods and results Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period ( p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction. Conclusion The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.


Drosophila Gene Expression Pattern Annotation Using Sparse Features and Term-Term Interactions.
The Drosophila gene expression pattern images document the spatial and temporal dynamics of gene expression and they are valuable tools for explicating the gene functions, interaction, and networks during Drosophila embryogenesis. To provide text-based pattern searching, the images in the Berkeley Drosophila Genome Project (BDGP) study are annotated with ontology terms manually by human curators. We present a systematic approach for automating this task, because the number of images needing text descriptions is now rapidly increasing. We consider both improved feature representation and novel learning formulation to boost the annotation performance. For feature representation, we adapt the bag-of-words scheme commonly used in visual recognition problems so that the image group information in the BDGP study is retained. Moreover, images from multiple views can be integrated naturally in this representation. To reduce the quantization error caused by the bag-of-words representation, we propose an improved feature representation scheme based on the sparse learning technique. In the design of learning formulation, we propose a local regularization framework that can incorporate the correlations among terms explicitly. We further show that the resulting optimization problem admits an analytical solution. Experimental results show that the representation based on sparse learning outperforms the bag-of-words representation significantly. Results also show that incorporation of the term-term correlations improves the annotation performance consistently.


Duration of mechanical ventilation in an adult intensive care unit after introduction of sedation and pain scales.
Sedation and analgesia scales promote a less-distressing experience in the intensive care unit and minimize complications for patients receiving mechanical ventilation. To evaluate outcomes before and after introduction of scales for sedation and analgesia in a general intensive care unit. A before-and-after design was used to evaluate introduction of the Richmond Agitation-Sedation Scale and the Behavioral Pain Scale for patients receiving mechanical ventilation. Data were collected for 6 months before and 6 months after training in and introduction of the scales. A total of 769 patients received mechanical ventilation for at least 6 hours (369 patients before and 400 patients after implementation). Age, scores on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and diagnostic groups were similar in the 2 groups, but the after group had more men than did the before group. Duration of mechanical ventilation did not change significantly after the scales were introduced (median, 24 vs 28 hours). For patients who received mechanical ventilation for 96 hours or longer (24%), mechanical ventilation lasted longer after implementation of the scales (P=.03). Length of stay in the intensive care unit was similar in the 2 groups (P= .18), but patients received sedatives for longer after implementation (P=.01). By logistic regression analysis, APACHE II score (P<.001) and diagnostic group (P<.001) were independent predictors of mechanical ventilation lasting 96 hours or longer. Sedation and analgesia scales did not reduce duration of ventilation in an Australian intensive care unit.


Phase II study of first-line (131)I-rituximab radioimmunotherapy in follicular non-Hodgkin lymphoma and prognostic (18)F-fluorodeoxyglucose positron emission tomography.
First-line (131)I-anti-CD20 radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) achieves durable remission with low toxicity. The phase II INITIAL study comprised 68 patients with follicular NHL followed up to 7 years (median 4 years) after outpatient (131)I-rituximab radioimmunotherapy (RIT) in conjunction with rituximab, followed by maintenance therapy for 1 year. Baseline and 3-month (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) imaging, analyzed according to Deauville criteria, was used to evaluate response and predict prognosis. The overall response rate at 3 months was 99%, with 88% achieving Deauville category 1-3. These satisfactory responders did not reach median time-to-next-treatment, versus a median of 29 months for a category 4-5 response (p < 0.0001). Grade IV hematological toxicity (9%) was self-limited without clinical sequelae. (131)I-rituximab radioimmunotherapy in newly diagnosed, advanced stage, symptomatic follicular NHL is an effective, practical and affordable alternative to existing conventional chemotherapies, with lower toxicity and durable remissions. Response assessment at 3 months by (18)F-FDG PET Deauville five-point scale permits prognostic stratification.


Changes in team cognition after a retention interval: the benefits of mixing it up.
This paper examines the retention of team cognition with changes in team membership. Hypotheses are developed from shared cognition and interactive team cognition theories. We report a study of the effects of Short (3-6 weeks) versus Long (10-13 weeks) retention intervals and change (Mixed) versus no change (Intact) in team membership during the interval on shared knowledge, team process, and team performance. The study context was a three-person Unmanned Aerial Vehicle (UAV) simulator. The long retention interval resulted in significantly lower team process scores and, except for the Short-Intact condition, all teams suffered a drop in performance after the break. However, those teams recovered prebreak levels of performance after one UAV mission. The counterintuitive result was that team mixing resulted in significant knowledge and process gains. An exploratory communication analysis indicated that Mixed team communication is longer in duration than Intact team communication, and Long-interval teams communicated more frequently than Short-interval teams. Unlike the Long-interval communication frequency effect, the Mixed team communication duration effect lasted throughout the experiment, suggesting greater interaction experience for Mixed teams. An exploratory mediation analysis indicated that the shared cognition Input-Process-Output framework was a good fit for the Intact team data, but not for the Mixed team data. We conclude that there are team-learning benefits of team mixing and that the interactive team cognition theory accounts better for those benefits than shared cognition theory.


Recent advances in two-dimensional intrinsic ferromagnetic materials Fe3X(X=Ge and Ga)Te2 and their heterostructures for spintronics.
Owing to their atomic thicknesses, atomically flat surfaces, long-range spin textures and captivating physical properties, two-dimensional (2D) magnetic materials, along with their van der Waals heterostructures (vdWHs), have attracted much interest for the development of next-generation spin-based materials and devices. As an emergent family of intrinsic ferromagnetic materials, Fe3X(X=Ge and Ga)Te2 has become a rising star in the fields of condensed matter physics and materials science owing to their high Curie temperature and large perpendicular magnetic anisotropy. Herein, we aim to comprehensively summarize the recent progress on 2D Fe3X(X=Ge and Ga)Te2 and their vdWHs and provide a panorama of their physical properties and underlying mechanisms. First, an overview of Fe3X(X=Ge and Ga)Te2 is presented in terms of crystalline and electronic structures, distinctive physical properties and preparation methods. Subsequently, the engineering of electronic and spintronic properties of Fe3X(X=Ge and Ga)Te2 by diverse means, including strain, gate voltage, substrate and patterning, is surveyed. Then, the latest advances in spintronic devices based on 2D Fe3X(X=Ge and Ga)Te2 vdWHs are discussed and elucidated in detail, including vdWH devices that exploit the exchange bias effect, magnetoresistance effect, spin-orbit torque effect, magnetic proximity effect and Dzyaloshinskii-Moriya interaction. Finally, the future outlook is given in terms of efficient large-scale fabrication, intriguing physics and important technological applications of 2D Fe3X(X=Ge and Ga)Te2 and their vdWHs. Overall, this study provides an overview to support further studies of emergent 2D Fe3X(X=Ge and Ga)Te2 materials and related vdWH devices for basic science and practical applications.


Magnesium-zinc scaffold loaded with tetracycline for tissue engineering application: In vitro cell biology and antibacterial activity assessment.
Recently, porous magnesium and its alloys are receiving great consideration as biocompatible and biodegradable scaffolds for bone tissue engineering application. However, they presented poor antibacterial performance and corrosion resistance which limited their clinical applications. In this study, Mg-Zn (MZ) scaffold containing different concentrations of tetracycline (MZ-xTC, x = 1, 5 and 10%) were fabricated by space holder technique to meet the desirable antibacterial activity and corrosion resistance properties. The MZ-TC contains total porosity of 63-65% with pore sizes in the range of 600-800 μm in order to accommodate bone cells. The MZ scaffold presented higher compressive strength and corrosion resistance compared to pure Mg scaffold. However, tetracycline incorporation has less significant effect on the mechanical and corrosion properties of the scaffolds. Moreover, MZ-xTC scaffolds drug release profiles show an initial immediate release which is followed by more stable release patterns. The bioactivity test reveals that the MZ-xTC scaffolds are capable of developing the formation of HA layers in simulated body fluid (SBF). Next, Staphylococcus aureus and Escherichia coli bacteria were utilized to assess the antimicrobial activity of the MZ-xTC scaffolds. The findings indicate that those scaffolds that incorporate a high level concentration of tetracycline are tougher against bacterial organization than MZ scaffolds. However, the MTT assay demonstrates that the MZ scaffolds containing 1 to 5% tetracycline are more effective to sustain cell viability, whereas MZ-10TC shows some toxicity. The alkaline phosphatase (ALP) activity of the MZ-(1-5)TC was considerably higher than that of MZ-10TC on the 3 and 7 days, implying higher osteoblastic differentiation. All the findings suggest that the MZ-xTC scaffolds containing 1 to 5% tetracycline is a promising candidate for bone tissue healing due to excellent antibacterial activity and biocompatibility.