Interaction of the anti-inflammatory annexin A1 protein and tacrolimus immunosuppressant in the renal function of rats.
Tacrolimus (FK) is currently widely used in transplant immunosuppression and the treatment of autoimmune diseases. However, FK induces nephrotoxicity which is characterized by functional and structural renal injury. The ubiquitous protein annexin A1 (ANXA1) has potent anti-inflammatory effects and protects against ischemia/reperfusion injury. We investigated the effects of exogenous ANXA1 treatment in an experimental model of acute FK nephrotoxicity. Munich-Wistar rats received a low-salt diet for 1 week and were randomized to treatment with ANXA1 (Ac2-26 peptide 0.5 mg/kg/day s.c.), FK (6 mg/kg/day p.o.), association (FK+ANXA1) and vehicles (1 ml/kg/day) for 7 days. FK induced a significant decrease in glomerular filtration rate and renal blood flow, and a significant increase in renal vascular resistance. In addition, FK caused extensive acute tubule-interstitial damage and an increase in anti-inflammatory ANXA1 expression in renal tissue. Exogenous ANXA1 treatment reduced FK-induced tubular dilatation and macrophage infiltration. For the first time, we observed that FK augmented ANXA1 expression in renal tissue. Exogenous ANXA1 treatment partially protected against FK-induced tubular injury and macrophage infiltration, and may be targeted in renal intervention strategies.


Prevalence and pattern of spinocerebellar degenerations in northeastern Libya.
An intensive search over a two-year period for cases of cerebellar and spinocerebellar degenerations in Benghazi, Libya, made through polyclinics, university hospitals and a centre for the handicapped, revealed a total of 52 patients, among whom 30 were index cases; the remainder were detected on family study. Twenty-five patients lived in Benghazi, giving a crude prevalence of 4.8/100 000 population. There were 24 patients (10 families) with hereditary spastic paraplegia (HSP), 13 (9 families) with early onset cerebellar ataxia with retained tendon reflexes (EOCA), 3 with Friedreich's ataxia (FA), 5 (1 family) with late onset cerebellar ataxia (LOCA) with pigmentary retinal degeneration and autosomal dominant inheritance, 6 single cases of LOCA and 1 with ataxia telangiectasia. There were 14 families with definite autosomal recessive inheritance and only 2 with dominant transmission. The large family size (average of 6.2 children per married woman in the patient group) and the high rate of consanguineous marriages contribute to the high incidence of familial cases, especially those with autosomal recessive inheritance. Nerve conduction studies were normal in HSP and abnormal in EOCA and FA. Computed tomographic scans revealed atrophy of the brainstem and cerebellum in 3 cases of EOCA and 2 with LOCA. No indigenous forms of the disease were observed and the clinical features differed little from the descriptions in literature. However, the relative rarity of patients with FA, in comparison with other types of hereditary ataxias, is striking.


"I Just Wanted Nothing More Than to Get in a Real Shower": Patient Experience of the Inpatient Wait for a Heart Transplant.
Patients waiting for heart transplant may be hospitalized for weeks to months before undergoing transplantation. This high-stress period is further complicated by restrictions of daily privileges including diet, rooming, access to the outdoors, and hygiene (eg, limited in ability to shower). However, there is a paucity of research on the experience of this waiting period. We sought to describe the inpatient experience among patients awaiting heart transplantation and to better understand the needs of inpatients waiting for heart transplant. We conducted in-depth, semistructured phone interviews with a purposeful sample of patients who received a heart transplant in the past 10 years and waited in the hospital for at least 2 weeks before surgery. Using the prior literature, the lived experience of the lead author, and input from qualitative experts, we developed an interview guide. Interviews were recorded, transcribed, and analyzed in an iterative process until theoretical saturation was achieved. A 3-person coding team identified, discussed, and reconciled emergent themes. We conducted interviews with 15 patients. Overarching themes included food, hygiene, relationship with health care professionals, living environment, and stressors. Patients reported that strong bonds were formed between the patients and the staff, and the overwhelming majority only had positive comments about these relationships. However, many expressed negative comments about the experience of the food and limitations in personal hygiene. Other stressors included the unknown length of the waiting period, lack of communication about position on the transplant list, worry about family, and concerns that their life must be saved by the death of another. Many participants described that they would benefit from more interaction with recent heart transplant recipients. Hospitals and care units have the opportunity to make small changes that could greatly benefit the experience of waiting for a heart transplant, as well as the experience of hospitalization more generally.


Vasopressin and vascular reactivity in the development of DOCA hypertension in rats with hereditary diabetes insipidus.
To examine the role of vasopressin (VP) in DOCA-salt hypertension, arterial pressure and renal vascular reactivity were studied in control Long-Evans (LE) rats and in Brattleboro rats homozygous for diabetes insipidus (DI rats). Vascular reactivity to norepinephrine, VP and angiotensin II was assessed in isolated kidneys perfused at constant flow. LE rats showed an increase in arterial pressure (AP) which was significant at 2 weeks post DOCA and averaged 180 mm Hg at 4 weeks. DI rats lacking VP showed no rise in AP after DOCA; however, DI rats given VP and DOCA developed hypertension with a course and magnitude similar to that observed in LE rats. At 6 to 10 weeks post DOCA, renal vascular reactivity to all agents was increased in LE rats and DI rats replaced with VP. Normotensive DI rats lacking VP showed depressed reactivity. Assessment of changes in reactivity at 3 days post DOCA showed that changes preceded the rise in AP. These data suggest that VP may play a primary role in the pathogenesis of DOCA hypertension and that its mechanism may involve an induction of increased vascular reactivity.


Re-Watching Lectures as a Study Strategy and Its Effect on Mind Wandering.
Material re-exposure (e.g., re-reading) is a popular mnemonic strategy, however, its utility has been questioned. We extend research on re-reading to re-watching - an emerging mnemonic technique given the increased use of recorded lectures today (e.g., in online courses). Consistent with findings from recent investigations of re-reading, there were no benefits of massed re-watching on memory for lecture material and re-watching increased rates of mind wandering. We discuss implications for understanding the cognitive consequences of re-exposure-based mnemonics.


Moniliella byzovii sp. nov., a chlamydospore-forming black yeast isolated from flowers.
Yeasts of the genus Moniliella were isolated from 651 flower samples collected in Vietnam, using an enrichment medium containing 50 % glucose. Species of the genus Moniliella were found in 5 % of the samples and 54 strains were isolated. The strains were identified based on D1/D2 LSU rRNA gene sequences as M. megachiliensis (15 strains), M. dehoogii (14 strains), and M. mellis (2 strains). The remaining 23 strains could not be reliably placed under any known species. Among them, 12 strains isolated from flowers of Ipomoea pes-caprae and Calotropis gigantea were peculiar for the intensive formation of chlamydospores. These strains could be subdivided into pigmented and non-pigmented groups. Both groups were identical in PCR fingerprints generated with primer (GAC)5 and in D1/D2 and ITS sequences. The yeast was closely related to M. fonsecae but differed from the latter by 52 nt (or 10.3 % of divergence) in the D1/D2 sequence and 71 nt (or 16.9 % of divergence) in the ITS sequence. The name Moniliella byzovii sp. nov. is proposed for this novel species. The type strain is TBY 2041.7(T) = CBS 12757(T) = NRRL Y-63661(T). The MycoBank number is MB 803186.


Reverse transformation of vole cells transformed by avian sarcoma virus containing the src gene.
Vole cells transformed by avian sarcoma virus carrying the src gene lose their fibroblastic morphology, the organized cytoskeletal system of the normal fibroblastic cell, the typical fibronectin deposit around the cell membrane, and the ability to shut off multiplication when suspended in liquid medium. All of these transformation characteristics are reversed by treatment with cAMP derivatives. Moreover, the cAMP treatment does not cause loss of activity of the src gene product. These data imply that cAMP exerts its effect at or after the point in the metabolic pathway affected by the src gene product, pp60src. Presumably, the decision to adopt the transformed or the normal state is determined by the degree to which the src gene or cAMP-mediated kinase activities respectively predominante in the cell. The development of all four transformation characteristics as a result of introduction of the src gene, and their coordinate reversal by cAMP derivatives, supports the previous thesis that in the normal vole or CHO fibroblast all four properties are part of a common regulatory system.


Cerebellar contribution to saccades and gaze holding: a modeling approach.
The possible role of the cerebellum for the control of saccades and gaze holding is reconsidered using a computational modeling approach. As suggested by previous research, control of gaze holding is assumed to be enhanced by the floccular lobe, whereas control of the saccadic pulse is governed by the oculomotor vermis and fastigial nucleus. In the present work, a negative feedback loop via the paramedian tract neurons and the floccular lobe that contains a forward model of the oculomotor plant is supposed to enhance the time constant of the brainstem integrator. Control of saccadic amplitude is hypothesized to be achieved by a more complex network: feedforward projections from the superior colliculus via the nucleus reticularis tegmenti pontis to the oculomotor vermis and fastigial nucleus cooperate with feedback connections from excitatory burst neurons to overcome the sluggishness of the assumed local feedback loop formed via the superior colliculus and to implement inverse dynamics of downstream neural and motor processing.


Regional variations in need for and provision and use of child health services in England and Wales.
An analysis of indicators of the need for and provision and use of child health services in the 15 pre- 1974 hospital board regions in England and Wales showed that need and provisions were badly matched. There was a high degree of correlation between the indices within each of the three groups, indicating that a region with a small provision in one area of child health services would tend to have few resources in other areas also. Statistics on the use of services relate more to the provision of those services than to the need for them. Regions with large resources will justify these resources by claiming that their use statistics indicate needs, whereas they really indicate met demands. It is more important to identify demands and needs that are not being met.


Isolation, identification, molecular and pathogenicity characteristics of an infectious laryngotracheitis virus from Hubei province, China.
Multiple outbreaks of avian infectious laryngotracheitis (ILT) in chickens, both domestically and internationally, have been directly correlate to widespread vaccine use in affected countries and regions. Phylogenetic and recombination event analyses have demonstrated that avian infectious laryngotracheitis virus (ILTV) field strains are progressively evolving toward the chicken embryo-origin (CEO) vaccine strain. Even with standardized biosecurity measures and effective prevention and control strategies implemented on large-scale farms, continuous ILT outbreaks result in significant economic losses to the poultry industry worldwide. These outbreaks undoubtedly hinder efforts to control and eradicate ILTV in the future. In this study, an ILTV isolate was successfully obtained by laboratory PCR detection and virus isolation from chickens that exhibited dyspnea and depression on a broiler farm in Hubei Province, China. The isolated strain exhibited robust propagation on chorioallantoic membranes of embryonated eggs, but failed to establish effective infection in chicken hepatocellular carcinoma (LMH) cells. Phylogenetic analysis revealed a unique T441P point mutation in the gJ protein of the isolate. Animal experiments confirmed the virulence of this strain, as it induced mortality in 6-wk-old chickens. This study expands current understanding of the epidemiology, genetic variations, and pathogenicity of ILTV isolates circulating domestically, contributing to the elucidate of ILTV molecular basis of pathogenicity and development of vaccine.


Asymmetric cytokinesis guide the development of pseudomonads in Rhynchospora pubera (Cyperaceae).
The late stages of microsporogenesis in the family Cyperaceae are marked by the formation of an asymmetrical tetrad, degeneration of three of the four nuclei resulting from meiosis and the formation of pseudomonads. In order to understand the cytological changes involved in the development of pseudomonads, a combination of 11 different techniques (conventional staining, cytochemistry procedures, immunofluorescence, FISH and transmission electron microscopy: TEM) were used to study the later stages of microsporogenesis in Rhynchospora pubera. The results demonstrated the occurrence of two cytoplasmic domains in the pseudomonads, one functional and the other degenerative, which are physically and asymmetrically separated by cell plate with an endomembrane system rich in polysaccharides. Other changes associated with endomembrane behaviour were observed, such as a large number of lipid droplets, vacuoles containing electron-dense material and concentric layers of endoplasmic reticulum. Concomitant with the isolation of degenerative nuclei, the tapetal cells also showed evidence of degeneration, indicating that both tissues under programmed cell death (PCD), as indicated by immunofluorescence and TEM procedures. The results are significant because they associate cellular polarisation and asymmetry with different cytoplasmic domains, and hence open new possibilities for studying cellular compartmentalisation and PCD.


Explanation and management of neurological disability.
Patients are often told of the diagnosis of a neurological disability in less than ideal circumstances such that they may not fully comprehend it. Clinicians must be able to sense when the patient's understanding is imperfect even if superficially he or she appears to take in what has been said and its implications. A programme of further counselling is often required to follow this up. A critical look at current procedures will show how these problems arise. It is suggested that improvements in the care of neurologically disabled patients would follow from improved communication between the many agencies that the concerned in their care and from providing books and other material explaining disability and its treatment. A logical development would be for disabled living centres to be established adjacent to existing neuroscience units.


Molecular dynamics simulation reveals preorganization of the chloroplast FtsY towards complex formation induced by GTP binding.
Two GTPases in the signal recognition particle (SRP) and SRP receptor (SR) interact with one another to mediate the cotranslational protein targeting pathway. Previous studies have shown that a universally conserved SRP RNA facilitates an efficient SRP-SR interaction in the presence of a signal sequence bound to SRP. However, a remarkable exception has been found in chloroplast SRP (cpSRP) pathway, in which the SRP RNA is missing. Based on biochemical and structural analyses, it is proposed that free cpSRP receptor (cpFtsY) has already been preorganized into a closed state for efficient cpSRP-cpFtsY association. However, no direct evidence has been reported to support this postulation thus far. In this study, we characterized the structural dynamics of cpFtsY and its conformational rearrangements induced by GTP binding using molecular dynamics (MD) simulations. Our results showed that the GTP-binding event triggered substantial conformational changes in free cpFtsY, including the relative orientation of N-G domain and several conserved motifs that are critical in complex formation. These rearrangements enabled the cpFtsY to relax into a preorganized 'closed' state that favored the formation of a stable complex with cpSRP54. Interestingly, the intrinsic flexibility of αN1 helix facilitated these rearrangements. In addition, GTP binding in cpFtsY was mediated by conserved residues that have been shown in other SRP GTPases. These findings suggested that GTP-bound cpFtsY could fluctuate into conformations that are favorable to form the stable complex, providing explanation of why SRP-SR interaction bypasses the requirement of the SRP RNA at a molecular level.


Oral hepatoprotective ability evaluation of purple sweet potato anthocyanins on acute and chronic chemical liver injuries.
In recent years, chemical liver injury cases increased significantly in Asian countries, and the imbalance in redox system was believed to be the main cause. Purple sweet potato anthocyanins (PSPA) have been shown to exert antioxidant activity and oxidative-stress-associated functional protein modulation through various signaling pathways, so it is considered to have the potential of liver injury preventive activity. In order to evaluate the hepatoprotective potency of PSPA according to its free radical scavenging and antioxidant effects, three acute chemical liver injury models were set up with ethanol, acetaminophen and carbon tetrachloride. PSPA at moderate and high doses obviously attenuated the tested serum biomarker levels and liver index in our experiments. Besides, one chronic liver injury model set up with carbon tetrachloride was also applied, in which PSPA was orally administrated after the liver damage had been formed. Both the serum biomarker levels and histopathological analysis showed that PSPA was able to attenuated chronic liver injury. Our experimental results demonstrated the potential of PSPA as an oral hepatoprotective agent against chemical liver injury from food plant.


More bang for your buck: super-adiabatic quantum engines.
The practical untenability of the quasi-static assumption makes any realistic engine intrinsically irreversible and its operating time finite, thus implying friction effects at short cycle times. An important technological goal is thus the design of maximally efficient engines working at the maximum possible power. We show that, by utilising shortcuts to adiabaticity in a quantum engine cycle, one can engineer a thermodynamic cycle working at finite power and zero friction. Our findings are illustrated using a harmonic oscillator undergoing a quantum Otto cycle.


Social Involvement in Religious Institutions and God-Mediated Control Beliefs: A Longitudinal Investigation.
This study examines the relationships among race, education, formal as well as informal involvement in the church, and God-mediated control. Formal involvement in the church was assessed by the frequency of attendance at worship services, Bible study groups, and prayer groups. Informal involvement was measured with an index of spiritual support provided by fellow church members. Data from a nationwide longitudinal survey of older people suggest that both formal and informal church involvement tend to sustain feelings of God-mediated control over time. The findings further reveal that compared to older whites, older African Americans are more likely to have stronger feelings of God-mediated control at the baseline survey and older blacks are more likely to sustain their sense of God-mediated control over time. In contrast, the data suggest that education is not significantly related to feelings of God-mediated control.


A pharmacokinetic interaction study of didanosine coadministered with trimethoprim and/or sulphamethoxazole in HIV seropositive asymptomatic male patients.
1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive treatments, each patient under fasting conditions received four of the following five treatments: 200 mg didanosine as a single agent; 200 mg trimethoprim + 1000 mg sulphamethoxazole; 200 mg trimethoprim + 200 mg didanosine; 1000 mg sulphamethoxazole + 200 mg of didanosine and; 200 mg trimethoprim + 1000 mg sulphamethoxazole + 200 mg didanosine. 3. Serial blood and urine samples were collected following the administration of each treatment. Plasma and urine samples were analyzed using high-pressure liquid chromatography (h.p.l.c.)/ultraviolet assays specific for unchanged didanosine, trimethoprim and/or sulphamethoxazole. 4. Percent urinary recovery (%UR) and renal clearance (CLR) emerged as consistently affected parameters, being decreased in the case of didanosine (35%, P = 0.016) and trimethoprim (32%, P = 0.019) and increased in the case of sulphamethoxazole (39%, P = 0.079), when all three agents were coadministered. The magnitude of the changes in didanosine CLR and %UR values was no greater when both trimethoprim and sulphamethoxazole were coadministered vs when each single agent was given with didanosine, suggesting that any effect was not additive. 5. Other key parameters such as Cmax, AUC, and t1/2 for didanosine (1309.9 ng ml-1, 1796.9 ng ml-1 h, and 1.61 h, respectively), trimethoprim (1.96 micrograms ml-1, 22.86 micrograms ml-1 h, and 9.03 h, respectively) or sulphamethoxazole (58.62 micrograms ml-1, 799.7 micrograms ml-1 h and 9.84 h, respectively) were not affected when didanosine was coadministered with either trimethoprim (didanosine: 1751.9 ng ml-1, 2158.0 ng ml-1 h, and 1.28 h; trimethoprim: 1.81 micrograms ml-1, 28.89 micrograms ml-1 h, and 11.4 h), sulphamethoxazole (didanosine: 1279.3 ng ml-1, 1793.2 ng ml-1 h, and 1.61 h; sulphamethoxazole: 53.57 micrograms ml-1, 732.1 micrograms ml-1 h, and 8.95 h), or the combination of trimethoprim and sulphamethoxazole (didanosine: 1283.7 ng ml-1, 1941.8 ng ml-1 h, and 1.38 h; trimethoprim: 1.59 micrograms ml-1, 26.68 micrograms ml-1 h, and 11.3 h; sulphamethoxazole: 59.48 micrograms ml-1, 760.9 micrograms ml-1 h, and 9.47 h). 6. Because the observed differences in CLR and %UR are small and not considered to be clinically relevant, it is not necessary to alter the dosing regimens of didanosine, trimethoprim or sulphamethoxazole when administered in combination to HIV seropositive patients.


Intraoperative acceleration measurements to quantify improvement in tremor during deep brain stimulation surgery.
Deep brain stimulation (DBS) surgery is extensively used in the treatment of movement disorders. Nevertheless, methods to evaluate the clinical response during intraoperative stimulation tests to identify the optimal position for the implantation of the chronic DBS lead remain subjective. In this paper, we describe a new, versatile method for quantitative intraoperative evaluation of improvement in tremor with an acceleration sensor that is mounted on the patient's wrist during surgery. At each anatomical test position, the improvement in tremor compared to the initial tremor is estimated on the basis of extracted outcome measures. This method was tested on 15 tremor patients undergoing DBS surgery in two centers. Data from 359 stimulation tests were acquired. Our results suggest that accelerometric evaluation detects tremor changes more sensitively than subjective visual ratings. The effective stimulation current amplitudes identified from the quantitative data (1.1 ± 0.8 mA) are lower than those identified by visual evaluation (1.7 ± 0.8 mA) for similar improvement in tremor. Additionally, if these data had been used to choose the chronic implant position of the DBS lead, 15 of the 26 choices would have been different. These results show that our method of accelerometric evaluation can potentially improve DBS targeting.


Rethinking neck-related arm pain: hypothetical clinical scenarios to differentiate the underlying IASP-defined pain mechanisms.
Neck-related arm pain is frequently encountered in clinical settings, yet its underlying pain mechanisms remain elusive. While such pain radiating from the neck to the arm is often attributed to injuries or diseases of the nervous system (neuropathic pain), it can also arise from nociceptive (referred) or nociplastic sources. Regrettably, patients exhibiting this specific pain distribution are frequently diagnosed with varying terms, including 'cervicobrachialgia', 'cervicobrachial neuralgia', 'cervicobrachial pain syndrome', and 'cervical radiculopathy'. The ambiguity surrounding these diagnostic labels complicates the clinical reasoning process. It is imperative for clinicians to discern and comprehend the dominant pain mechanism. Three distinct hypothetical clinical scenarios depict patients with almost identical pain distribution but divergent dominant pain mechanisms. Within these scenarios, both subjective and objective examinations are employed to elucidate the dominant pain mechanism associated with neck-related arm pain: nociceptive, neuropathic, and nociplastic. Furthermore, clinicians must remain aware that the dominant pain mechanism can evolve over time.


18F-FDG PET/CT is an ideal imaging modality for the early diagnosis of relapsing polychondritis: A case report.
Relapsing polychondritis (RP) is a rare autoimmune disease of unknown etiology that may affect multiple cartilage throughout the body. We report on a middle-aged man presented with cough, chest tightness, and fever of unknown origin, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) was performed. And the imaging shows multiple increased FDG accumulation in tracheobronchial tree and all intercostal cartilages, as well as in nasal, right auricule, laryngeal cartilage. Based on the findings, the diagnosis of RP was made. Our case demonstrates that FDG PET/CT is an useful diagnostic tool to accurately determine the extent of inflammation throughout the body and to guiding the selection of a biopsy site.


High-Concentration Self-Assembly of Zirconium- and Hafnium-Based Metal-Organic Materials.
Metal-organic frameworks (MOFs) are crystalline, porous solids constructed from organic linkers and inorganic nodes that are promising for applications in chemical separations, gas storage, and catalysis, among many others. However, a major roadblock to the widespread implementation of MOFs, including highly tunable and hydrolytically stable Zr- and Hf-based frameworks, is their benchtop-scalable synthesis, as MOFs are typically prepared under highly dilute (≤0.01 M) solvothermal conditions. This necessitates the use of liters of organic solvent to prepare only a few grams of MOF. Herein, we demonstrate that Zr- and Hf-based frameworks (eight examples) can self-assemble at much higher reaction concentrations than are typically utilized, up to 1.00 M in many cases. Combining stoichiometric amounts of Zr or Hf precursors with organic linkers at high concentrations yields highly crystalline and porous MOFs, as confirmed by powder X-ray diffraction (PXRD) and 77 K N2 surface area measurements. Furthermore, the use of well-defined pivalate-capped cluster precursors avoids the formation of ordered defects and impurities that arise from standard metal chloride salts. These clusters also introduce pivalate defects that increase the exterior hydrophobicity of several MOFs, as confirmed by water contact angle measurements. Overall, our findings challenge the standard assumption that MOFs must be prepared under highly dilute solvothermal conditions for optimal results, paving the way for their scalable and user-friendly synthesis in the laboratory.


Prerequisites for tissue specific and position independent expression of a gene locus in transgenic mice.
The elucidation of general parameters influencing the transcriptional activation of gene loci at distinct stages of development is an essential prerequisite for a reproducibly successful gene transfer in both gene therapy protocols and biotechnology. Up to now research has focused mostly on the identification and characterization of individual cis-regulatory elements by transient transfection and in vitro assays. However, the most relevant assay system to test gene constructs designed for gene therapy protocols is the transgenic animal. In such an experimental system exogenous genes are usually integrated randomly in the chromatin. For gene constructs not fulfilling the requirements for correct gene locus activation this can lead to genomic position effects on gene expression. The consequences are highly variable expression levels and a disturbance of temporal and spatial expression patterns. Hence it is important to examine how cis-elements function in a chromatin context, and how they cooperate during the developmentally controlled activation of an entire gene locus. One among a few gene loci which are sufficiently characterized to enable such investigations is the chicken lysozyme locus. This review summarizes recent results aimed at identifying the necessary prerequisites for a reproducibly correct expression of the lysozyme locus in transgenic mice and the implications of our findings for gene transfer. The complete lysozyme locus is expressed independent of the chromosomal position and at a high level in macrophages of transgenic mice. Correct transgene regulation requires the cooperation of all cis-regulatory elements. Chromatin of the lysozymes locus in both the active and the inactive state is highly structured. Each cis-regulatory element on the chicken lysozyme locus is organized in its own unique chromatin environment, with nucleosomes specifically placed on specific sequences. The transcriptional activation of the lysozyme locus is accompanied by extensive rearrangements of its chromatin structure, which are disturbed when the transgenes are subjects to genomic position effects. Based on these results, we propose that a complete locus is resistant to genomic position effects, and that a distinct chromatin architecture of a gene locus is required for its correct activation.


Semi-Rigid Ureteroscopy Should Not Be the First Option for Proximal Ureteral Stones in Children.
To investigate the factors that predict the success and complication rates of semi-rigid ureteroscopy (URS) in pediatric population. This is a retrospective analysis of the database including 182 patients who underwent URS between 2001 and 2016. The possible factors that might affect the outcome were age, gender, stone laterality, largest stone size, number of stones, stone location, orifice dilatation status, and caliber of ureteroscope. The mean age was 68.1 (7-204) months, and male-to-female ratio was 94:88. Operative side was left for 97, right for 82, and bilateral for 3 patients. One hundred and forty-four patients had a single stone, and 38 patients had multiple stones. The median largest stone size was 7 (2-20) mm. Postoperative ureteral stenting was performed in 150 (86.2%) patients. The overall success rate was 84.6%, while 81.6% and 85.4% in 8F URS and 4.5F URS groups, respectively (p = 0.560). Stone-free rate was higher among patients who were older than 36 months, distal ureteral stones and single stones (p = 0.012, 0.002, and 0.009, respectively). Complication rate was higher for proximally located stones (p = 0.029). The mean follow-up was 23.9 ± 32.5 months. URS is a safe procedure with acceptable success rates in the pediatric population. Younger age, multiple stones, and proximal location are the predisposing factors for failure, whereas proximal location was the only factor for complication occurrence. Therefore, semi-rigid ureteroscopy should not be the first choice in the treatment of proximal ureteral stones, and alternative methods should be preferred, if available.


Human health alters the sustainability of fishing practices in East Africa.
Understanding feedbacks between human and environmental health is critical for the millions who cope with recurrent illness and rely directly on natural resources for sustenance. Although studies have examined how environmental degradation exacerbates infectious disease, the effects of human health on our use of the environment remains unexplored. Human illness is often tacitly assumed to reduce human impacts on the environment. By this logic, ill people reduce the time and effort that they put into extractive livelihoods and, thereby, their impact on natural resources. We followed 303 households living on Lake Victoria, Kenya over four time points to examine how illness influenced fishing. Using fixed effect conditional logit models to control for individual-level and time-invariant factors, we analyzed the effect of illness on fishing effort and methods. Illness among individuals who listed fishing as their primary occupation affected their participation in fishing. However, among active fishers, we found limited evidence that illness reduced fishing effort. Instead, ill fishers shifted their fishing methods. When ill, fishers were more likely to use methods that were illegal, destructive, and concentrated in inshore areas but required less travel and energy. Ill fishers were also less likely to fish using legal methods that are physically demanding, require travel to deep waters, and are considered more sustainable. By altering the physical capacity and outlook of fishers, human illness shifted their effort, their engagement with natural resources, and the sustainability of their actions. These findings show a previously unexplored pathway through which poor human health may negatively impact the environment.


Fast and faster: a designed variant of the B-domain of protein A folds in 3 microsec.
We have introduced the mutation glycine 29 to alanine, designed to increase the rate of protein folding, into the B-domain of protein A (BdpA). From NMR lineshape analysis, we find the G29A mutation increases the folding rate constant by threefold; the folding time is 3 microsec. Although wild-type BdpA folds extremely fast, simple-point mutations can still speed up the folding; thus, the folding rate is not evolutionarily maximized. The short folding time of G29A BdpA (the shortest time yet reported) makes it an attractive candidate for an all-atom molecular dynamics simulation that could potentially show a complete folding reaction starting from an extended chain. We also constructed a fluorescent variant of BdpA by mutating phenylalanine 13 to tryptophan, allowing fluorescence-based time-resolved temperature-jump measurements. Temperature jumps and NMR complement each other, and give a very complete picture of the folding kinetics.


Modeling the water use efficiency of soybean and maize plants under environmental stresses: application of a synthetic model of photosynthesis-transpiration based on stomatal behavior.
Understanding the variability of plant WUE and its control mechanism can promote the comprehension to the coupling relationship of water and carbon cycle in terrestrial ecosystem, which is the foundation for developing water-carbon coupling cycle model. In this paper, we made clear the differences of net assimilation rate, transpiration rate, and WUE between the two species by comparing the experiment data of soybean (Glycine max Merr.) and maize (Zea mays L.) plants under water and soil nutrient stresses. WUE of maize was about two and a half times more than that of soybean in the same weather conditions. Enhancement of water stresses led to the marked decrease of Am and Em of two species, but water stresses of some degree could improve WUE, and this effect was more obvious for soybean. WUE of the two species changed with psiL in a second-order curve relation, and the WUE at high fertilization was higher than that at low fertilization, this effect was especially obvious for maize. Moreover, according to the synthetic model of photosynthesis-transpiration based on stomatal behavior (SMPTSB) presented by Yu et al. (2001), the WUE model and its applicability were discussed with the data measured in this experiment. The WUE estimated by means of the model accorded well with the measured values. However, this model underestimated the WUE for maize slightly, thus further improvement on the original model was made in this study. Finally, by discussing some physiological factors controlling Am and WUE, we made clear the physiological explanation for differences of the relative contributions of stomata- and mesophyll processes to control of Am and WUE, and the applicability of WUE model between the two species. Because the requirement to stomatal conductance by unit change of net assimilation rate is different, the responses of opening-closing activity of stomata to environmental stresses are different between the two species. To obtain the same level of net assimilation rate, soybean has to open its stomata more widely to keep small stomatal resistance, as compared with maize.


Factors affecting metabolic cost of transport during a multi-stage running race.
The aim of this study was to investigate: (1) the role of , the fraction of (F) and the metabolic cost of transport (CoT) in determining performance during an ultra-endurance competition and (2) the effects of the race on several biomechanical and morphological parameters of the lower limbs that are likely to affect CoT. Eleven runners (aged 29-54 years) participated in an ultra-endurance competition consisting of three running stages of 25, 55 and 13 km on three consecutive days. Anthropometric characteristics, body composition, morphological properties of the gastrocnemius medialis, maximal explosive power of the lower limb and were determined before the competition. In addition, biomechanics of running and CoT were determined, before and immediately after each running stage. Performance was directly proportional to (r=0.77) and F (r=0.36), and inversely proportional to CoT (r=-0.30). Low CoT values were significantly related to high maximal power of the lower limbs (r=-0.74) and vertical stiffness (r=-0.65) and low footprint index (FPI, r=0.70), step frequency (r=0.62) and external work (r=0.60). About 50% of the increase in CoT during the stages of the competition was accounted for by changes in FPI, which represents a global evaluation of medio-lateral displacement of the foot during the whole stance phase, which in turn is associated with the myotendinous characteristics of the lower limb. Thus, lower CoT values were related to greater muscular power and lower FPI, suggesting that a better ankle stability is likely to achieve better performance in an ultra-endurance running competition.


Precise determination of seawater calcium using isotope dilution inductively coupled plasma mass spectrometry.
We describe a method for rapid, precise and accurate determination of calcium ion (Ca(2+)) concentration in seawater using isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). A 10 μL aliquot of seawater was spiked with an appropriate (43)Ca enriched solution for (44)Ca/(43)Ca ID-ICP-MS analyses, using an Element XR (Thermo Fisher Scientific), operated at low resolution in E-scan acquisition mode. A standard-sample bracketing technique was applied to correct for potential mass discrimination and ratio drift at every 5 samples. A precision of better than 0.05% for within-run and 0.10% for duplicate measurements of the IAPSO seawater standard was achieved using 10 μL solutions with a measuring time less than 3 minutes. Depth profiles of seawater samples collected from the Arctic Ocean basin were processed and compared with results obtained by the classic ethylene glycol tetra-acetic acid (EGTA) titration. Our new ID-ICP-MS data agreed closely with the conventional EGTA data, with the latter consistently displaying 1.5% excess Ca(2+) values, possibly due to a contribution of interference from Mg(2+) and Sr(2+) in the EGTA titration. The newly obtained Sr/Ca profiles reveal sensitive water mass mixing in the upper oceanic column to reflect ice melting in the Arctic region. This novel technique provides a tool for seawater Ca(2+) determination with small sample size, high throughput, excellent internal precision and external reproducibility.


Molecular docking and site-directed mutagenesis of a Bacillus thuringiensis chitinase to improve chitinolytic, synergistic lepidopteran-larvicidal and nematicidal activities.
Bacterial chitinases are useful in the biocontrol of agriculturally important pests and fungal pathogens. However, the utility of naturally occurring bacterial chitinases is often limited by their low enzyme activity. In this study, we constructed mutants of a Bacillus thuringiensis chitinase with enhanced activity based on homology modeling, molecular docking, and the site-directed mutagenesis of target residues to modify spatial positions, steric hindrances, or hydrophilicity/hydrophobicity. We first identified a gene from B. thuringiensis YBT-9602 that encodes a chitinase (Chi9602) belonging to glycosyl hydrolase family 18 with conserved substrate-binding and substrate-catalytic motifs. We constructed a structural model of a truncated version of Chi9602 (Chi9602(35-459)) containing the substrate-binding domain using the homologous 1ITX protein of Bacillus circulans as the template. We performed molecular docking analysis of Chi9602(35-459) using di-N-acetyl-D-glucosamine as the ligand. We then selected 10 residues of interest from the docking area for the site-directed mutagenesis experiments and expression in Escherichia coli. Assays of the chitinolytic activity of the purified chitinases revealed that the three mutants exhibited increased chitinolytic activity. The ChiW50A mutant exhibited a greater than 60 % increase in chitinolytic activity, with similar pH, temperature and metal ion requirements, compared to wild-type Chi9602. Furthermore, ChiW50A exhibited pest-controlling activity and antifungal activity. Remarkable synergistic effects of this mutant with B. thuringiensis spore-crystal preparations against Helicoverpa armigera and Caenorhabditis elegans larvae and obvious activity against several plant-pathogenic fungi were observed.


A consensus approach to the formulation of guidelines for laboratory testing and reporting of antiphospholipid antibody assays.
Despite numerous past and ongoing efforts, there remains significant variation in results from assays for the major antiphospholipid antibodies (aPL), namely anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and lupus anticoagulant (LA). There is therefore a need to produce comprehensive guidelines on laboratory testing and reporting of aPL assays. However, because of the paucity of good-quality published evidence, there is a heavy reliance on expert opinion, and thus the existing consensus guidelines for aPL testing and reporting are largely eminence based rather than evidence based. This may potentially bias recommendations to reflect the personal preferences of those who have the greatest influence during the guideline formulation process. This article largely details the experience of the Australasian Anticardiolipin Working Party in undertaking a consensus approach to formulation of guidelines on aCL and anti-beta2GPI testing and reporting, including measures taken to minimize these issues. Despite the time-consuming nature of the process, given the paucity of good-quality published evidence, formulation of guidelines by the consensus process remains an important initiative to improve the standardization of aPL testing and reporting.


An unusual familial dementia associated with G131V PRNP mutation.
Gerstmann-Struassler-Scheinker disease is one of the familial prion diseases secondary to mutations in the prion protein gene (PRNP). The clinical phenotype has a diverse spectrum and might show variation among cases with the same genotype. We report a patient with G131V mutation in the PRNP gene, who was initially considered to harbor familial Alzheimer's disease, based on the family history, clinical presentation and imaging findings. A case with a G131V mutation in the PRNP gene is described, and the literature is reviewed. A 35-year-old man presented with personality changes, behavioral disturbances and cognitive complaints. A similar clinical phenotype was reported in the patient's father, a paternal uncle and a paternal aunt. In conjunction with the observation of mild cerebral atrophy on magnetic resonance imaging and hypometabolism in bilateral temporal and parietal lobes on positron-emission tomography studies, the diagnosis was initially considered as familial Alzheimer's disease. However, whole-exome sequencing of the index patient, confirmed with Sanger sequencing in his father and uncle, revealed the presence of a heterozygous G131V variant in the PRNP gene. To the best of our knowledge, this is the third report of a G131V mutation in the PRNP gene in the literature. Although ataxia and extrapyramidal findings accompanied dementia in patients reported in the previous literature, the members of the family in the present case primarily reported cognitive impairment, underscoring the importance of genetic evaluation in familial early-onset dementia patients, regardless of clinical and imaging features suggestive of alternative pathologies.


Malaria vector control: from past to future.
Malaria is one of the most common vector-borne diseases widespread in the tropical and subtropical regions. Despite considerable success of malaria control programs in the past, malaria still continues as a major public health problem in several countries. Vector control is an essential part for reducing malaria transmission and became less effective in recent years, due to many technical and administrative reasons, including poor or no adoption of alternative tools. Of the different strategies available for vector control, the most successful are indoor residual spraying and insecticide-treated nets (ITNs), including long-lasting ITNs and materials. Earlier DDT spray has shown spectacular success in decimating disease vectors but resulted in development of insecticide resistance, and to control the resistant mosquitoes, organophosphates, carbamates, and synthetic pyrethroids were introduced in indoor residual spraying with needed success but subsequently resulted in the development of widespread multiple insecticide resistance in vectors. Vector control in many countries still use insecticides in the absence of viable alternatives. Few developments for vector control, using ovitraps, space spray, biological control agents, etc., were encouraging when used in limited scale. Likewise, recent introduction of safer vector control agents, such as insect growth regulators, biocontrol agents, and natural plant products have yet to gain the needed scale of utility for vector control. Bacterial pesticides are promising and are effective in many countries. Environmental management has shown sufficient promise for vector control and disease management but still needs advocacy for inter-sectoral coordination and sometimes are very work-intensive. The more recent genetic manipulation and sterile insect techniques are under development and consideration for use in routine vector control and for these, standardized procedures and methods are available but need thorough understanding of biology, ethical considerations, and sufficiently trained manpower for implementation being technically intensive methods. All the methods mentioned in the review that are being implemented or proposed for implementation needs effective inter-sectoral coordination and community participation. The latest strategy is evolution-proof insecticides that include fungal biopesticides, Wolbachia, and Denso virus that essentially manipulate the life cycle of the mosquitoes were found effective but needs more research. However, for effective vector control, integrated vector management methods, involving use of combination of effective tools, is needed and is also suggested by Global Malaria Control Strategy. This review article raises issues associated with the present-day vector control strategies and state opportunities with a focus on ongoing research and recent advances to enable to sustain the gains achieved so far.


Latest progress in constructing solid-state Z scheme photocatalysts for water splitting.
Artificial Z scheme photocatalysis has been considered as a promising strategy for producing the clean energy source of hydrogen gas. The core of the Z scheme is a two-step excitation process in a tandem structured photosystem aiming to satisfy both the criteria of wide range solar spectrum absorption and strong thermodynamic driving force for photolysis reactions. Therefore, efficient connection and matching between the two photosystems is the key to improve the photocatalytic activity. Recently, new progress has been achieved concerning the principles and applications of state-of-the-art solid-state Z schematic systems to enhance the photocatalytic efficiency and repress competitive reactions. This review summarizes the latest approaches to all-solid-state Z schemes for photocatalytic water splitting, including new tandem structures, new morphologies, and new connection modes to improve light absorption as well as carrier transportation. The challenges for developing novel high performance Z scheme photocatalysts are also discussed.


An experimental study of electro-acupuncture on auditory impairment caused by kanamycin in guinea pigs.
Frequency following response (FFR) and auditory brain stem evoked potential response (ABR) were used to determine the auditory acuity in evaluating the effect of electro-acupuncture treatment of kanamycin-induced auditory impairment in guinea pigs. The succinate dehydrogenase (SDH) activity and morphological changes of the inner ear receptors were examined under the light and scanning electron microscope in cochlear spread preparations. The results showed that 1) electro-acupuncture was effective but no significant differences were found among the stimulating wave forms; 2) Tinggong (SI 19), Yifeng (SJ 17), Shenshu (UB 23), Sanyinjiao (Sp 6), Zhubin (K 9) and Waiguan (SJ 5) are all effective acupoints, especially the combination of Tinggong (SI 19), Sanyinjiao (Sp 6) and Zhubin (K 9) acupoints; 3) improvement in the cochlear function and excitability of the cortical and lower auditory center and increase of the mitochondrial SDH activity and energy supply in hair cells might contribute to the mechanism of the treatment.


The effects of exercise on the immune system and stress hormones in sportswomen.
Despite the numerous studies controversial results exist in specific immune response to exercise. The aim of this study was to determining the differences in the humoral immune parameters, serum ACTH and cortisol levels existing between sportswomen and sedentary subjects and the effect of acute aerobic and anaerobic exercise on these parameters. 40 sportswomen (Groups 1 and 2) and 20 sedentary women (Group 3) were enrolled and Group 1 performed aerobic exercise on a treadmill for 30 minutes while the Group 2 was subjected to the Wingate effort test for 30 seconds. Before exercising (at 8.30 a.m), immediately after the exercise, and 4 hours, days 2 and 5 days after exercising blood samples were obtained and the levels of IgA, IgG, IgM, complement 3 (C3) and complement 4 (C4) were determined turbidometrically. Before exercise: the means of IgA and IgG values in the G1 and G2 groups were higher than the Group G3, and the mean cortisol levels in the sedentary group was significantly higher (p<0.05). After Exercise: Whereas the C3 and C4 levels decreased significantly at the end of the exercise in Group 1 and 2 (p<0.05), the IgA, IgG (p<0.05) and IgM levels (p<0.01) at the 4th and 5th determinations were observed to be significantly higher in only the Group 1. The cortisol and ACTH levels were found to have increased significantly (p<0.05) in the Group 1. In Group 2, no changes were observed in the IgA, IgG and IgM levels. We conclude that regular and moderate exercise has favorable effects on the immune system by increasing immunoglobulins which are potent protective factors.


An annual survey of successful suicide incidence in hamadan, Western iran.
Suicide has constituted a critical public health problem for many decades. The number of completed suicide is traditionally high in Iran. The objective of the present study was to describe the patterns of methods of suicide among registered deaths due to suicide in Hamada, western Iran. In this cross-sectional study, all completed suicide cases (n=146) were included from March 2004 through March 2005 based on Hamadan's Forensic center registered deaths because of suicide. Supplementary data were gauged through a questionnaire from the attempters' relatives. All statistical analyses were performed using version 13 of the statistical software package SPSS and an alpha level of .05 for all statistical tests. Prevalence of completed suicide was 8.3 per 100,000 in Hamadan, Iran. From 146 cases, the male-to-female ratio was 7.1:1. Average age of cases was 33.9 yr (Min=10, Max=94) across all age groups, males show consistently higher completed suicide rates than females. Of the 69.2% were from urban population versus 30.8% form rural population. The most common method of suicide was hanging (78.1 %). Other common methods were poisoning (11.6%), and self-burning (6.2%). Suicide rate in Hamadan is high among males through hanging which can be due tosubstance dependency and unemployment.


Plant foods in the management of diabetes mellitus: vegetables as potential hypoglycaemic agents.
Vegetables are among the numerous plant adjuncts tried for the treatment of diabetes mellitus. A few vegetables that are commonly consumed in India have been claimed to possess antidiabetic potency. In recent years, there has been a renewed interest to screen such plant food materials, for a possible beneficial use. Considerable amount of work has been carried out in this regard with bitter gourd (Momordica charantia) and ivy gourd (Coccinia indica) both in experimental animals and human diabetic subjects. Majority of these studies have documented the beneficial effect of the fruit of bitter gourd and leaf of ivy gourd when administered orally as a single dose. The hypoglycaemic influence is claimed to be mediated through an insulin secretagogue effect or through an influence on enzymes involved in glucose metabolism. The limited number of studies on other vegetables such as cabbage (Brassica oleracia), green leafy vegetables, beans and tubers have shown the beneficial hypoglycaemic influence in both experimental animals and humans. There is scope for more extensive research in this area, especially to examine the long term beneficial effect of dietary vegetables, to identify the active principle, and to understand the mechanism of action, which is at present unclear. Since diet forms the mainstay in the management of diabetes mellitus, there is scope for exploiting the antidiabetic potency of vegetables to the maximum extent. Such plant food adjuncts possessing hypoglycaemic activity appear to hold promise as potential antidiabetic agents.


[Value of automatic sutures in total gastrectomy for cancer: apropos of 81 patients].
We reviewed the results of stapled circular (EEA) and linear (TA 30 or 55) anastomoses in a prospective study of 40 total gastrectomies for cancer, using an interposed jejunal limb (Henley technique). There were 63 circular anastomoses: 40 esophago-jejunal, 20 jejuno-duodenal and 3 jejuno-jejunal anastomoses. Forty patients were submitted to 41 linear stapled closures of the jejunal stump. Technical failure rate with stapled anastomoses was 5% (3 out of 63). Incidence of anastomotic leak was 6.3% for all the circular stapled anastomoses tried and 5% if the 3 technical failures were excluded. Anastomotic leakage is more often associated to splenopancreatectomy. One patient (1% of all the anastomoses) presented gastro-intestinal bleeding, related to the suture line. A conservative treatment was carried out successfully. The mean follow-up time of the surviving patients was 27 +/- 20 months: there was a 5.5% rate of late anastomotic stenosis; all the patients were cured by esophageal dilations. Late anastomotic stenosis is directly related to associated cobalt therapy. Analysis of an older retrospective series of 41 hand-sutured total gastrectomies allowed a comparison to be made between stapled and sutured anastomoses in total gastrectomy for cancer.


Application of a microtiter cell-culture method to characterization of avian adenoviruses.
A microtiter cell-culture method was developed and used to titrate virus isolates for characterization. Virus dilutions and chicken kidney cell suspensions were dispensed into the wells of disposable microculture plates, with infectivity endpoints being determined microscopically on the fifth or sixth day, or by reading crystal-violet-stained monolayers on day 6. With this method, 37 candidate avian adenoviruses isolated from diagnostic accessions were characterized as avian adenoviruses (AAV). The criteria used for characterization were production of round-cell cytopathic effect, resistance to chloroform treatment, inhibition by 5-bromodeoxyuridine, and the presence of an antigen showing identity with a known AAV by precipitation in agar gel. Statistical anlaysis of eight replicate titrations of three AAV indicated that the titration method was highly reproducible. Use of the microculture method for titrations gave substantial savings in indicator cells, media, incubator space, culture dishes, and time.


Temperature-jump solution X-ray scattering reveals distinct motions in a dynamic enzyme.
Correlated motions of proteins are critical to function, but these features are difficult to resolve using traditional structure determination techniques. Time-resolved X-ray methods hold promise for addressing this challenge, but have relied on the exploitation of exotic protein photoactivity, and are therefore not generalizable. Temperature jumps, through thermal excitation of the solvent, have been utilized to study protein dynamics using spectroscopic techniques, but their implementation in X-ray scattering experiments has been limited. Here, we perform temperature-jump small- and wide-angle X-ray scattering measurements on a dynamic enzyme, cyclophilin A, demonstrating that these experiments are able to capture functional intramolecular protein dynamics on the microsecond timescale. We show that cyclophilin A displays rich dynamics following a temperature jump, and use the resulting time-resolved signal to assess the kinetics of conformational changes. Two relaxation processes are resolved: a fast process is related to surface loop motions, and a slower process is related to motions in the core of the protein that are critical for catalytic turnover.


Corrected QT Interval (QTc) Diagnostic App for the Oncological Routine: Development Study.
Numerous antineoplastic drugs such as chemotherapeutics have cardiotoxic side effects and can lead to long QT syndrome (LQTS). When diagnosed and treated in time, the potentially fatal outcomes of LQTS can be prevented. Therefore, regular electrocardiogram (ECG) assessments are critical to ensure patient safety. However, these assessments are associated with patient discomfort and require timely support of the attending oncologist by a cardiologist. This study aimed to examine whether this approach can be made more efficient and comfortable by a smartphone app (QTc Tracker), supporting single-lead ECG records on site and transferring to a tele-cardiologist for an immediate diagnosis. To evaluate the QTc Tracker, it was implemented in 54 cancer centers in Germany. In total, 266 corrected QT interval (QTc) diagnoses of 122 patients were recorded. Moreover, a questionnaire on routine ECG workflow, turnaround time, and satisfaction (1=best, 6=worst) was answered by the centers before and after the implementation of the QTc Tracker. Compared to the routine ECG workflow, the QTc Tracker enabled a substantial turnaround time reduction of 98% (mean 2.67, 95% CI 1.72-2.67 h) and even further time efficiency in combination with a cardiologic on-call service (mean 12.10, 95% CI 5.67-18.67 min). Additionally, nurses and patients reported higher satisfaction when using the QTc Tracker. In particular, patients' satisfaction sharply improved from 2.59 (95% CI 2.41-2.88) for the routine ECG workflow to 1.25 (95% CI 0.99-1.51) for the QTc Tracker workflow. These results reveal a significant improvement regarding reduced turnaround time and increased user satisfaction. Best patient care might be guaranteed as the exposure of patients with an uncontrolled risk of QTc prolongations can be avoided by using the fast and easy QTc Tracker. In particular, as regular side-effect monitoring, the QTc Tracker app promises more convenience for patients and their physicians. Finally, future studies are needed to empirically test the usability and validity of such mobile ECG assessment methods. ClinicalTrials.gov NCT04055493; https://classic.clinicaltrials.gov/ct2/show/NCT04055493.


The chaperoning and assistance roles of the HIV-1 nucleocapsid protein in proviral DNA synthesis and maintenance.
In the following three sections we will briefly review the seminal roles of the HIV-1 nucleocapsid protein NCp7 in the fate of the HIV-1 full length RNA from genomic RNA in a dimeric form to the proviral DNA. Emphasis will be given to the mechanisms of NC-directed assistance to the genomic RNA and reverse transcriptase in the course of proviral DNA synthesis and to DNA integrity at the end of the polymerization process, and to the NC-assisted repair and recombination reactions fueling the viability and variability of the virus.


Bifunctional metal-salen complexes as efficient catalysts for the fixation of CO2 with epoxides under solvent-free conditions.
A bifunctional cobalt-salen complex containing a Lewis acidic metal center and a quaternary phosphonium salt unit anchored on the ligand effectively catalyzes the synthesis of cyclic carbonates from CO2 and epoxides under mild conditions without the utilization of additional organic solvents or co-catalysts. The effects of various reaction variables on the catalytic performance were studied in detail and indicate an optimized reaction temperature of about I00 degrees C and CO2 pressure of around 4 MPa, although the reaction proceeds smoothly even at pressures as low as 2 MPa. The catalyst is applicable to a variety of epoxides, producing the corresponding cyclic carbonates in good yields in most cases. Furthermore, the catalyst can be easily recovered and reused several times without significant loss of its catalytic activity. This process thus represents a greener pathway for the environmentally benign chemical fixation of CO2 to produce cyclic carbonates.


Demographical profile and clinical features of patients with bipolar disorder in an outpatient setting in Singapore.
Bipolar disorder, or manic depressive psychosis, is a psychiatric disorder characterised by extreme changes in mood, thinking, energy and behaviour. Western studies on this condition show a delay in diagnosis and treatment. The aim of this study is to examine the demographical profile and clinical features of this group of patients in Singapore to see if there is a similar delay. Data of patients diagnosed with this condition and treated in two separate outpatient practices in the private sector from January 1999 to October 2003 were retrieved from case files and analysed. Of the 121 patients with bipolar disorder treated, there were 45 percent male and 55 percent female patients, and most of them were in the 20-39 year age group. Chinese formed the largest ethnic group while Malays were underrepresented. 58 percent were employed, and 48 percent were married. While the age of onset of illness ranged mainly from age 10 to 29 years, the age when they first sought treatment was from 20 to 39 years. A duration of illness of more than two years was found in 79 percent of these patients. In terms of diagnostic categories, 17 percent were bipolar I, 76 percent were bipolar II and 7 percent of the bipolar disorders, not otherwise specified. The first episode presented was depression in 75 percent and bipolar disorder was the initial diagnosis in only 34 percent of the cases. A delay in the correct diagnosis for more than two years accounted for 34 percent of the cases. Only 17 percent had a family history of bipolar disorder. 28 percent had a history of antidepressant-induced manic episodes and 17 percent had a previous episode of mixed state. Psychotic symptoms were absent in 75 percent, and 65 percent had never been hospitalised for their condition. Nine percent had made a past suicide attempt and 39 percent had a comorbid diagnosis. 46 percent were treated with a combination of mood stabilizers, neuroleptics and antidepressants and 16 percent had electroconvulsive therapy. Only 34 percent were in full remission of their illness. There was a preponderance towards the younger age groups for the age of onset, and the type of first episode was typically depression. There was a significant delay in diagnosis and treatment of patients with bipolar disorder. These features were strikingly similar to Western studies. Bipolar II was the diagnostic category seen more than bipolar I in the outpatient setting. Polypharmacy was the norm and a large group of patients did not achieve full remission.


BS-SEM evaluation of the tissular interactions between cortical bone and calcium-phosphate covered titanium implants.
The improvement of the reliability of the contact between the osseous tissues and the implant materials has been tested by recovering the metallic implants with ceramic materials, usually calcium phosphates. In our study, the calcium phosphate recovering layers were deposited by means of a pulsed-laser deposition technique. Our aim was to to evaluate the tissue interactions established between cortical bone and titanium implants covered by five different layers, ranging from amorphous calcium phosphate to crystalline hydroxyapatite, obtained by altering the parameters of the laser ablation process. The surgical protocol of the study consisted in the simultaneous implantation of the five types of implants in both the tibial dyaphisis of three Beagle dogs, sacrificed respectively one, two and three months after the last surgical procedures. After the sacrifice, the samples were submitted to a scheduled procedure of embedding in plastic polymers without prior decalcification, in order to perform the ultrastructural studies: scanning microscopy with secondary and backscattered electrons (BS-SEM). Our observations show that both in terms of the calcified tissues appearing as a response to the presence of the different coatings and of time of recovering, the implants coated with crystalline calcium phosphate layers by laser ablation present a better result than the amorphous-calcium-phosphate-coated implants. Moreover, the constant presence of chondroid tissue, related with the mechanical induction by forces applied on the recovering area, strongly suggests that the mechanisms implied in osteointegration are related to endomembranous, rather than endochondral ossification processes.


Colonization of rice and Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) larvae by genetically modified endophytic Methylobacterium mesophilicum.
The colonization of Spodoptera frugiperda J.E. Smith larvae and rice seedlings by genetically modified endophytic bacterium Methylobacterium mesophilicum, and also the possible transfer of this bacterium to inside the larva's body during seedlings consumption were studied. The data obtained by bacterial reisolation and fluorescence microscopy showed that the bacterium colonized the rice seedlings, the larva's body and that the endophytic bacteria present in seedlings could be acquired by the larvae. In that way, the transference of endophytic bacterium from plants to insect can be a new and important strategy to insect control using engineered microorganisms.


Nonlocal image editing.
In this paper, we introduce a new image editing tool based on the spectrum of a global filter computed from image affinities. Recently, it has been shown that the global filter derived from a fully connected graph representing the image can be approximated using the Nyström extension. This filter is computed by approximating the leading eigenvectors of the filter. These orthonormal eigenfunctions are highly expressive of the coarse and fine details in the underlying image, where each eigenvector can be interpreted as one scale of a data-dependent multiscale image decomposition. In this filtering scheme, each eigenvalue can boost or suppress the corresponding signal component in each scale. Our analysis shows that the mapping of the eigenvalues by an appropriate polynomial function endows the filter with a number of important capabilities, such as edge-aware sharpening, denoising, tone manipulation, and abstraction, to name a few. Furthermore, the edits can be easily propagated across the image.


Mechanobiological Strategies to Enhance Stem Cell Functionality for Regenerative Medicine and Tissue Engineering.
Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.


IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction.
Myocardial contractile dysfunction accompanies both systemic and cardiac insults. Septic shock and burn trauma can lead to reversible contractile deficits, whereas ischemia and direct inflammation of the heart can precipitate transient or permanent impairments in contractility. Many of the insults that trigger contractile dysfunction also activate the innate immune system. Activation of the innate immune response to infection is coordinated by the conserved Toll/interleukin-1 (IL-1) signal transduction pathway. Interestingly, components of this pathway are also expressed in normal and failing hearts, although their function is unknown. The hypotheses that Toll/IL-1 signaling occurs in the heart and that intact pathway function is required for contractile dysfunction after different insults were tested. Results from these experiments demonstrate that lipopolysaccharides (LPS) activate Toll/IL-1 signaling and IL-1 receptor-associated kinase-1 (IRAK1), a critical pathway intermediate in the heart, indicating that the function of this pathway is not limited to immune system tissues. Moreover, hearts lacking IRAK1 exhibit impaired LPS-triggered downstream signal transduction. Hearts from IRAK1-deficient mice also resist acute LPS-induced contractile dysfunction. Finally, IRAK1 inactivation enhances survival of transgenic mice that develop severe myocarditis and lethal heart failure. Thus the Toll/IL-1 pathway is active in myocardial tissue and interference with pathway function, through IRAK1 inactivation, may represent a novel strategy to protect against cardiac contractile dysfunction.


Modifying the physicochemical properties of pea protein by pH-shifting and ultrasound combined treatments.
The effect of a pH-shifting and ultrasound combined process on the functional properties and structure of pea protein isolate (PPI) was investigated. PPI dispersions were adjusted to pH 2, 4, 10, or 12, treated by power ultrasound for 5min, and incubated for 1h before the sample pH was brought back to neutral. After treatment, water solubility, protein aggregate size, solution turbidity, surface hydrophobicity (Ho), free sulfhydryl content (SH), and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the soluble PPI were determined. pH-shifting at pH 12 and ultrasound combined treatment (pH12-US) significantly improved protein properties, while property modification of the samples treated under acidic conditions was less pronounced. The pH12-US treated PPI had a solubility seven times higher than the control, reaching an average particle size of 45.2nm. In addition, the pH12-US treated PPI significantly improved Ho due to disulfide bonds disruption, and produced more protein sub-units than other treatments. The soluble PPI obtained through this process may be a promising emulsifier for the enrichment of fat-soluble nutrients in foods.


[Urolithiasis in clinical practice. Occurrence, etiology, investigation and preventive treatment].
The author reviews the epidemiological, etiological aspects of stone disease of the urinary tract, and prophylactic treatment. The occurrence of urolithiasis has increased considerably since the second world war and now affects 10% of the adult male and 4% of the adult female population. In Norway the yearly incidence of patients presenting with urinary stone colic in general practice is two per 1,000 inhabitants. Urinary calculi form when the concentration of the crystal-forming substances such as calcium oxalate, calcium phosphate, uric acid and cystine exceed their solubility. Important risk factors for stone formation are low fluid intake and high consumption of animal protein. Etiological examination and stone prophylactic treatment should reflect the most prevalent types of stone disease. An examination programme that probably can reveal one or several causes of the stone disease in about 60-70% of the patients is described. The recommended examinations car be performed in general practice. Prophylactic treatment in terms of dietary advice and fluid intake is suggested. In patients with a high recurrence rate of stone formation prophylactic drug treatment with tiazid or alluopurinol should be considered. The beneficial effect of the treatment is well documented.


Trauma center care is associated with reduced readmissions after injury.
Trauma center care has been associated with improved mortality. It is not known if access to trauma center care is also associated with reduced readmissions. We hypothesized that receiving treatment at a trauma center would be associated with improved care and therefore would be associated with reduced readmission rates. We conducted a retrospective analysis of all hospital visits in California using the Office of Statewide Health Planning and Development Database from 2007 to 2008. All hospital admissions and emergency department visits associated with injury were longitudinally linked. Regions were categorized by whether they had trauma centers. We excluded all patients younger than 18 years. We performed univariate and multivariate regression analyses to determine if readmissions were associated with patient characteristics, length of stay for initial hospitalization, trauma center access, and triage patterns. A total of 211,504 patients were included in the analysis. Of these, 5,094 (2%) died during the index hospitalization. Of those who survived their initial hospitalization, 79,123 (38%) experienced one or more readmissions to any hospital within 1 year. The majority of these were one-time readmissions (62%), but 38% experienced multiple readmissions. Over 67% of readmissions were unplanned and 8% of readmissions were for a trauma. After controlling for patient variables known to be associated with readmissions, primary triage to a trauma center was associated with a lower odds of readmission (odds ratio, 0.89; p < 0.001). The effect of transport to a trauma center remained significantly associated with decreased odds of readmission at 1 year (odds ratio, 0.96; p < 0.001). Readmissions after injury are common and are often unscheduled. While patient factors play a role in this, care at a trauma center is also associated with decreased odds for readmission, even when controlling for severity of injury. This suggests that the benefits of trauma center care extend beyond improvements in mortality to improved long-term outcomes. Epidemiologic study, level III; therapeutic/care management study, level IV.


Environmental impact assessment of solid waste management in Beijing City, China.
The environmental impacts of municipal solid waste management in Beijing City were evaluated using a life-cycle-based model, EASEWASTE, to take into account waste generation, collection, transportation, treatment/disposal technologies, and savings obtained by energy and material recovery. The current system, mainly involving the use of landfills, has manifested significant adverse environmental impacts caused by methane emissions from landfills and many other emissions from transfer stations. A short-term future scenario, where some of the landfills (which soon will reach their capacity because of rising amount of waste in Beijing City) are substituted by incinerators with energy recovery, would not result in significant environmental improvement. This is primarily because of the low calorific value of mixed waste, and it is likely that the incinerators would require significant amounts of auxiliary fuels to support combustion of wet waste. As for the long-term future scenario, efficient source separation of food waste could result in significant environmental improvements, primarily because of increase in calorific value of remaining waste incinerated with energy recovery. Sensitivity analysis emphasized the importance of efficient source separation of food waste, as well as the electricity recovery in incinerators, in order to obtain an environmentally friendly waste management system in Beijing City.


Model-based identification of PEEP titrations during different volemic levels.
A cardiovascular system (CVS) model has previously been validated in simulated cardiac and circulatory disease states. It has also been shown to accurately capture all main hemodynamic trends in a porcine model of pulmonary embolism. In this research, a slightly extended CVS model and parameter identification process are presented and validated in a porcine experiment of positive end-expiratory pressure (PEEP) titrations at different volemic levels. The model is extended to more physiologically represent the separation of venous and arterial circulation. Errors for the identified model are within 5% when re-simulated and compared to clinical data. All identified parameter trends match clinically expected changes. This work represents another clinical validation of the underlying fundamental CVS model, and the methods and approach of using them for cardiovascular diagnosis in critical care.


Implications of retroviral and oncogene activity in chronic myelogenous leukemia.
Chronic myelogenous leukemia (CML) is a stem cell disease which, on a clinical level, progresses from the release from growth control of normally differentiated cells (a preleukemic state) to an acute leukemia. On a molecular level, the evolution of CML to acute leukemia is a multistep process. We propose that an early step, at the stem cell level, is acquisition of the ability for gene movement, which allows subsequent submicroscopic and chromosomal rearrangements that cause changes in the growth characteristics and regulation of the stem cell. A specific platelet DNA polymerase (PDP - reverse transcriptase) may play a role in gene movement. The characteristic reciprocal translocation of chromosomes #9 and #22, causing the activation of the c-abl oncogene, appears to be responsible for the uncontrolled cellular growth. Yet, other growth factors (e.g., platelet derived growth factor) and activated oncogenes (e.g., c-sis) must be responsible for the stimulation, progression, and variability seen during the course of the disease. Because CML is a progressive disease with clinically definable stages, CML appears to be a model system for the study of the molecular basis of the progression of preleukemia to leukemia specifically, and preneoplasia to aggressive neoplasia in general.


Cognitive and clinical indicators of employment assistance needs from a national survey of individuals living with psychosis.
The aim of this secondary analysis was to explore global functioning, course of illness (the number of episodes since onset and the degree of recovery between episodes), duration of illness, and cognitive ability as potential indicators of the extent of employment assistance needs. A secondary analysis of Australia's second national survey of psychosis was undertaken. Screening for psychosis took place during March, 2010 at 7 national locations, within public mental health services and nongovernment organizations. Next, 1,825 of the 7,955 who screened positive for psychosis were randomly selected and completed face-to-face interviews. Of those, 1,619 also completed the Digit Symbol Coding Test (DSCT), a measure of current general cognitive ability. In epidemiological surveys, employment status is an important proxy indicator of employment assistance needs. The strongest correlates of any versus no employment in the current survey were: global functioning as represented by Personal and Social Performance Scale (PSP) total score, age, general cognitive ability as represented by DSCT scores, course of illness, and educational attainment. These correlates persisted following adjustment in a multivariate model. Subject to the limitations identified, global functioning, cognitive ability, and course of illness were the most promising clinical and cognitive indicators of more intensive employment assistance needs. The demographic variables age and educational attainment indicated additional labor market disadvantage, which could also help to identify those more likely to need intensive employment assistance. These results inform further investigations aimed at developing a practical measure of employment-related psychiatric disability. (PsycINFO Database Record


Investigating Multimodal Diagnostic Eye Biomarkers of Cognitive Impairment by Measuring Vascular and Neurogenic Changes in the Retina.
Previous studies have demonstrated that cognitive impairment (CI) is not limited to the brain but also affects the retina. In this pilot study, we investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with CI using a low-cost multimodal approach. Quantification of the retinal structure and function were conducted for every subject (n = 69) using advanced retinal imaging, full-field electroretinogram (ERG) and visual performance exams. The retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment software. The Montreal Cognitive Assessment was used to measure CI. Pearson product moment correlation was performed between variables. Of the 69 participants, 32 had CI (46%). We found significantly altered microvascular network in individuals with CI (larger venular-asymmetry factor: 0.7 ± 0.2) compared with controls (0.6 ± 0.2). The vascular fractal dimension was lower in individuals with CI (capacity, information and correlation dimensions: D0, D1, and D2 (mean ± SD): 1.57 ± 0.06; 1.56 ± 0.06; 1.55 ± 0.06; age 81 ± 6years) vs. controls (1.61 ± 0.03; 1.59 ± 0.03; 1.58 ± 0.03; age: 80 ± 7 years). Also, drusen-like regions in the peripheral retina along with pigment dispersion were noted in subjects with mild CI. Functional loss in color vision as well as smaller ERG amplitudes and larger peak times were observed in the subjects with CI. Pearson product moment correlation showed significant associations between the vascular parameters (artery-vein ratio, total length-diameter ratio, D0, D1, D2 and the implicit time (IT) of the flicker response but these associations were not significant in the partial correlations. This study illustrates that there are multimodal retinal markers that may be sensitive to CI decline, and adds to the evidence that there is a statistical trend pointing to the correlation between retinal neuronal dysfunction and microvasculature changes suggesting that retinal geometric vascular and functional parameters might be associated with physiological changes in the retina due to CI. We suspect our analysis of combined structural-functional parameters, instead of individual biomarkers, may provide a useful clinical marker of CI that could also provide increased sensitivity and specificity for the differential diagnosis of CI. However, because of our study sample was small, the full extent of clinical applicability of our approach is provocative and still to be determined.


Mode conversion via wavefront shaping.
In recent years, wavefront shaping has been utilized to control and correct distorted light for enhancing a bright spot, generation of a Bessel beam or darkening a complete area at the output of a scattering system. All these outcomes can be thought of as enhancing a particular mode of the output field. In this letter, we study the relation between the attainable enhancement factor, corresponding to the efficiency of mode conversion, and the field distribution of the target mode. Working in the limit of a thin diffuser enables not only a comparison between experimental and simulated results, but also allows for derivation of an analytic formula. These results shed light on the ability to use a scattering medium as a mode converter and on the relationship between the desired shape and the efficiency.


Prey availability affects daily torpor by free-ranging Australian owlet-nightjars (Aegotheles cristatus).
Food availability, ambient temperatures (T(a)), and prevailing weather conditions have long been presumed to influence torpor use. To a large extent, this is based on measurements in the laboratory of animals placed on restricted diets and kept at low T (a). Information on the determinants of torpor employment in the field is limited. We assessed winter torpor by insectivorous, free-ranging Australian owlet-nightjars (Aegotheles cristatus; 22 birds, 834 bird-days over six winters). Birds in three habitats were investigated to test whether torpor use is affected by annual T(a), rainfall, and arthropod abundance. Owlet-nightjars entered daily torpor regularly at all sites. Torpor frequency, depth and bout duration were greatest during two periods with lower arthropod abundance, providing rare evidence of the link between food availability and torpor patterns of wild birds. Temporal organization of torpor was similar among sites, and nocturnal torpor was more frequent than previously reported. Our findings quantitatively demonstrate that reduced food resources affect torpor usage independently from T(a), and support the view that food availability is a primary ecological determinant of torpor use in the wild.


[Distribution and spatial ordering of biopolymer molecules in resting bacterial spores].
The presence, distribution and spatial arrangement of biopolymers in situ were studied in both a total intact spore and in a certain cellular layer using a spectroscopic technique of attenuated total refraction (ATR-IR) in the IR region. In contrast to vegetative cells, intact spores were characterized by isotropic distribution of protein components. This feature can be regarded as an index of the cryptobiotic state of spores. However, the distribution of protein components among individual layers of a spore was anisotropic. Bonds characterized by amide I and amide II bands were most often ordered in a layer which comprised cellular structures from the exosporium to the inner spore membrane.


Early T1 Myocardial MRI Mapping: Value in Detecting Myocardial Hyperemia in Acute Myocarditis.
Background Hyperemia is a key component of acute myocarditis (AM). Early gadolinium uptake because of myocardial hyperemia may be quantified by using T1 mapping. Purpose To evaluate the value of early enhanced T1 shortening for the diagnosis of acute myocarditis. Materials and Methods Study participants suspected of having AM and healthy control (HC) participants were prospectively enrolled from September 2016 to May 2019. Participants underwent 1.5-T cardiac MRI including Lake Louise criteria, T2 mapping, native T1, and extracellular volume, with the addition of early enhanced T1 mapping (2 minutes after intravenous administration of 0.15 mmol/kg gadobutrol). Color-coded maps of the percentage of T1 shortening from precontrast to early postcontrast were generated. Optimal early T1 shortening cut-off value and its diagnostic performance in the identification of acute myocarditis were calculated. Results Forty-five study participants with AM (median age, 40 years; interquartile range [IQR], 20-46 years; 22 women) diagnosed according to multidisciplinary clinical evaluation, electrocardiography, laboratory test, echocardiography, cardiac MRI, and coronary CT and/or invasive angiography. Findings were confirmed by endomyocardial biopsy in 64% (29 of 45) of participants. MRI parameters were compared with 19 HC participants (median age, 39 years; IQR, 28-46 years; seven women). Median early T1 shortening was 75% (IQR, 72%-78%) in participants with AM versus 65% (IQR, 61%-66%) in HC participants (P < .001). Early T1 shortening showed high diagnostic performance (area under the receiver operating characteristic curve [AUC], 0.97; 95% confidence interval [CI]: 0.94, 1.00) and excellent interobserver reproducibility (intraclass correlation coefficient: 0.98; 95% CI: 0.96, 1.00). Early T1 shortening of 70% or greater identified acute myocarditis with 93% sensitivity, 100% specificity, and 95% diagnostic accuracy. Early T1 shortening had better diagnostic performance than late percentage T1 shortening (AUC, 0.97 vs 0.90, respectively; P = .03) and extracellular volume (AUC, 0.97 vs 0.88, respectively; P = .046), and similar to native T1 (AUC, 0.97 vs 0.93, respectively; P = .63) and T2 mapping (AUC, 0.97 vs 0.97, respectively; P > .99). Conclusion In this proof-of-concept study, percentage of T1 shortening at early enhanced T1 mapping showed high accuracy for the diagnosis of acute myocarditis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by De Cecco and Monti in this issue.


Point transect sampling along linear features.
Distance sampling is a widely used methodology for assessing animal abundance. A key requirement of distance sampling is that samplers (lines or points) are placed according to a randomized design, which ensures that samplers are positioned independently of animals. Often samplers are placed along linear features such as roads, so that bias is expected if animals are not uniformly distributed with respect to distance from the linear feature. We present an approach for analyzing distance data from a survey when the samplers are points placed along a linear feature. Based on results from a simulation study and from a survey of Irish hares in Northern Ireland conducted from roads, we conclude that large bias may result if the position of samplers is not randomized, and analysis methods fail to account for nonuniformity.


Forgotten family members: the importance of siblings in early psychosis.
This paper reviews the evidence on the significance of sibling inclusion in family interventions and support during early psychosis. This narrative review presents the current research related to the importance of family work during early psychosis, the needs and developmental significance of siblings during adolescence and early adulthood, the protective effects of sibling relationships, and the characteristics of early psychosis relevant to the sibling experience. It will also review the evidence of the sibling experience in chronic physical illness and disability, as well as long-term psychotic illness. Despite the evidence that working with families is important during early psychosis, siblings have been largely ignored. Siblings are an important reciprocal relationship of long duration. They play an important role in development during adolescence and early adulthood. These relationships may be an underutilized protective factor due to their inherent benefits and social support. Developmental theories imply that early psychosis could negatively impact the sibling relationship and their quality of life, effecting personality development and health outcomes. The evidence shows that adolescent physical illness or disability has a significantly negative impact on the sibling's quality of life and increases the risk for the onset of mental health issues. Long-term psychotic illness also results in negative experiences for siblings. Current evidence shows that siblings in early psychosis experience psychological distress and changes in functional performance. Further research using standard measures is required to understand the impact early psychosis has on the sibling relationship and their quality of life.


A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer.
Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC.


Local linear estimation of concordance probability with application to covariate effects models on association for bivariate failure-time data.
Bivariate survival analysis has wide applications. In the presence of covariates, most literature focuses on studying their effects on the marginal distributions. However covariates can also affect the association between the two variables. In this article we consider the latter issue by proposing a nonstandard local linear estimator for the concordance probability as a function of covariates. Under the Clayton copula, the conditional concordance probability has a simple one-to-one correspondence with the copula parameter for different data structures including those subject to independent or dependent censoring and dependent truncation. The proposed method can be used to study how covariates affect the Clayton association parameter without specifying marginal regression models. Asymptotic properties of the proposed estimators are derived and their finite-sample performances are examined via simulations. Finally, for illustration, we apply the proposed method to analyze a bone marrow transplant data set.