The absence of fans removes the home advantage associated with penalties called by National Hockey League referees.
The COVID-19 pandemic has had a major impact on professional sports, notably, forcing the National Hockey League to hold its 2020 playoffs in empty arenas. This provided an unprecedented opportunity to study how crowds may influence penalties awarded by referees in an ecological context. Using data from playoff games played during the COVID-19 pandemic and the previous 5 years (n = 547), we estimate the number of penalties called by referees depending on whether or not spectators were present. The results show an interaction between a team's status (home; away) and the presence or absence of crowds. Post-hoc analyses reveal that referees awarded significantly more penalties to the away team compared to the home team when there is a crowd present. However, when there are no spectators, the number of penalties awarded to the away and home teams are not significantly different. In order to generalize these results, we took advantage of the extension of the pandemic and the unusual game setting it provided to observe the behavior of referees during the 2020-2021 regular season. Again, using data from the National Hockey League (n = 1639), but also expanding our sample to include Canadian Hockey League games (n = 1709), we also find that the advantage given to the home team by referees when in front of a crowd fades in the absence of spectators. These findings provide new evidence suggesting that social pressure does have an impact on referees' decision-making, thus contributing to explain the phenomenon of home advantage in professional ice hockey.


The role of pleasantness and activation-based well-being in performance prediction.
This study examined the relationships between 2 measures of psychological well-being and work performance using the circumplex model of emotion as the theoretical framework. Although the pleasantness-based measure of well-being predicted subsequent work performance, the results failed to establish a relationship between the activation-based measure of well-being and work performance. Future directions and implications of the findings regarding the further refinement of the role of psychological well-being in performance prediction are introduced.


Uremic thrombocytopathy is not about urea.
Platelet dysfunction in renal failure is attributable to high levels of small, partly dialyzable molecules known as uremic toxins, hence the term "uremic thrombocytopathy." Although a variety of moieties contribute to platelet dysfunction or abnormal interactions between platelets and the vascular wall, urea remains a potential factor. Here, we studied three family members with familial azotemia, a rare autosomal dominant syndrome characterized by high plasma urea resulting from impaired urinary excretion but normal renal function otherwise. Platelet function, assessed in vitro and by traditional bleeding time, was normal in all individuals. Abnormal platelet function in patients with renal failure is not caused by high concentrations of urea.


The complex regional pain syndrome: Diagnosis and management strategies.
Complex regional pain syndrome (CRPS) is a chronic disease that affects a limb following an injury or trauma. The CRPS associated with symptoms, including severe pain, swelling, as well as changes in skin color and temperature. Treatment of CRPS requires a multidisciplinary approach, with a focus on personalized treatment plans and addressing psychological factors. This review provides an overview of updates in the diagnosis and treatment of CRPS. There are clinical criteria for diagnosing CRPS, including persistent pain and swelling. The CRPS can also be diagnosed with imaging and laboratory tests. Novel insights into treatment approaches for CRPS have been gained from advances in understanding its pathophysiology. Treatment of CRPS includes both pharmacological and non-pharmacological interventions. The latest guidelines for CRPS treatment emphasize the importance of early diagnosis and intervention, personalized treatment plans, and addressing psychological factors in managing CRPS.


Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas.
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs). Using brain-seeking patient-derived melanoma cells and real-time in vivo imaging, we show a widespread distribution of micrometastases and macrometastases in the brain, recapitulating the progression of multifoci metastases seen in patients. We armed MSCs with different oHSV variants (MSC-oHSV) and found that intracarotid administration of MSC-oHSV, but not of purified oHSV alone, effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor-bearing mice. In a syngeneic model of melanoma brain metastasis, a combination of MSC-oHSV and PD-L1 blockade increases IFNγ-producing CD8+ tumor-infiltrating T lymphocytes and results in a profound extension of the median survival of treated animals. This study thus demonstrates the utility of MSCs as OV carriers to disseminated brain lesions, and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.


Ultrasonographic-surgical correlation of ankle tendon tears.
This study evaluates the accuracy of ultrasonography in detecting ankle tendon tears of the peroneal, posterior tibial, and flexor digitorum longus tendons based on operative findings and clinical follow-up. A prospective study was performed in 33 patients with clinically suspected tendon injury. Sixty-eight tendons were evaluated sonographically. The diagnosis of an intrasubstance tear was made when disruption of uniform tendon architecture by hypoechoic linear or globular clefts was observed. Criteria used to diagnose complete tendon rupture included discontinuity or gap within the tendon or complete nonvisualization of the tendon. Treatment decisions were based on a combination of clinical parameters and imaging studies. Twenty-six patients had the presence or absence of tear confirmed at surgery. Five patients had a final diagnosis based on clinical findings, and two were lost to follow-up. Of the 68 tendons evaluated sonographically, 54 were directly inspected at surgery; 20 were found to be torn and 34 were intact. Ultrasonography was able to identify all tears correctly with an accuracy of 93%, a sensitivity of 100%, and a specificity of 88%. The positive and negative predictive values were 83% and 100%, respectively. The combined accuracy, sensitivity, and specificity of ultrasonography in detecting tendon tears in all patients evaluated both surgically and by clinical follow-up were 94%, 100%, and 90%, respectively.


Functional genetic mouse models: promising tools for investigation of the proteolytic internet.
Knockout mice are the gold standard to probe for the role of a specific protease within the interacting network of proteases, substrates, and inhibitors. This proteolytic network, or protease web, determines cell signaling and organ homeostasis. Therefore, protease deficiency or inhibition is intrinsically tied to alterations within this network, always leading to new molecular phenotypes, which define susceptibility of an organ to disease. Furthermore, recent hints, mainly from research on matrix metalloproteinases, about the impact of the protease web on inter-organ signaling molecules suggest the existence of a proteolytic internet of communicating local organ- or molecular polymorphism-specific networks, thereby defining homeostasis and disease susceptibility in the whole organism.


The-2548G/A polymorphism in the human leptin gene promoter region is associated with plasma free leptin levels; interaction with adiposity and gender in healthy subjects.
A common -2548G/A promoter variant of the human leptin gene has recently been shown to be associated with variations in circulating leptin levels but available data are still conflicting. The aim of this study was to explore potential associations between the -2548G/A polymorphism and adiposity-related variables, plasma total leptin levels, as well as soluble leptin receptor (sOB-R) levels and free leptin in a group of healthy Greek subjects. One hundred eighteen consecutively enrolled subjects [62 females, 56 males; mean age+/-SD: 17.7+/-1.8 years; body mass index (BMI) range: 15.4-35.9 kg/m2] were genotyped for the -2548G/A polymorphism and their BMI, fat free mass, % fat mass, fasting plasma total leptin and sOB-R levels were determined. The ratio leptin/sOB-R was used as an index of free leptin. No significant differences in genotype and allele frequencies of the -2548G/A polymorphism were detected between normal weight and overweight subjects, and no association was found between this polymorphism and BMI, fat mass or plasma total leptin levels. However, the -2548G/A polymorphism was found to be associated with circulating free leptin levels in a gender specific manner. More specifically, compared to carriers of the -2548G allele, female subjects with the A/A genotype had higher age and fat mass adjusted mean (+/-SE) plasma concentrations of sOB-R (32.9+/-7.2 vs. 25.6+/-3.8 ng/ml, P=0.05), and significantly lower (approx. 50%) leptin/sOB-R values (0.74+/-0.25 vs. 1.42+/-0.13, P=0.02). Furthermore, multiple regression analysis revealed that, after adjustment to fat mass, the -2548G/A genotype and gender are significantly associated with free leptin index in the entire study sample. Similar regression models revealed a significant interaction of gender and genotype when considered in addition to fat mass, or fat mass and genotype when considered in addition to gender, as predictors of free leptin index. In conclusion, the common -2548G/A promoter variant of the human leptin gene is associated with plasma free leptin levels through an interaction with adiposity and gender in healthy subjects.


Canine rabies ecology in southern Africa.
Rabies is a widespread disease in African domestic dogs and certain wild canine populations. Canine rabies became established in Africa during the 20th century, coinciding with ecologic changes that favored its emergence in canids. I present a conceptual and terminologic framework for understanding rabies ecology in African canids. The framework is underpinned by 2 distinct concepts: maintenance and persistence. Maintenance encompasses the notion of indefinite transmission of infection within a local population and depends on an average transmission ratio > or =1. Maintenance in all local populations is inherently unstable, and the disease frequently becomes extinct. Persistence, the notion of long-term continuity, depends on the presence of rabies in > or =1 local population within the canine metapopulation at any time. The implications for understanding rabies ecology and control are reviewed, as are previous studies on rabies ecology in African canids.


The velic traverse: an independent oral articulator?
Two speech functions have traditionally been ascribed to the velum: opening and closing the velopharyngeal port and providing a passive surface against which the tongue can produce oral constrictions. Contrary to this passive oral function, the present x-ray study finds that a substantial portion of the velum moves to constrict the oropharyngeal isthmus for French uvular /ʁ/. This substructure, designated the velic traverse, functions independently of the parts of the velum used for velopharyngeal port closure, thus acting as an oral articulator. An active velic traverse challenges methods for estimating vocal tract shapes based on tongue posture alone.


Postbariatric Brachioplasty with Posteromedial Scar: Physical Model, Technical Refinements, and Clinical Outcomes.
Brachioplasty is an increasingly performed procedure following massive weight loss. A visible scar is the main hindrance to this surgery. The aims of the study were to develop a physical model to investigate the ideal location of the surgical incision and to present the authors' technical refinements with the posteromedial scar approach. Twenty-four postbariatric patients underwent brachioplasty with posteromedial scar placement, concomitant liposuction, fascial plication, and axillary Z-plasty. Skin specimens were tested and a physical model of the arm was set up to investigate the difference in mechanical stress on the posteromedial and medial scars. The validated Patient and Observer Scar Assessment Scale, the Vancouver Scar Scale, and a questionnaire assessing subjective improvements were administered to patients. Preoperative and postoperative photographs were assessed by three independent plastic surgeons. The physical model showed that stress intensity and distribution along the scar were reduced in the posteromedial location, with smaller scar displacement in the loading simulations. Twenty-three patients healed uneventfully. One (4.1 percent) had a 2-cm dehiscence. Mean Patient and Observer Scar Assessment Scale scores were, respectively, 2 ± 0.76 and 2.13 ± 0.64 in the patients' and observers' questionnaires. The mean Vancouver Scar Scale value was 3.5 ± 1.7. Questionnaires assessing the subjective outcomes showed a mean value of 3.45 ± 0.63 of 4. The surgeons' assessment resulted in a score of 4.5 ± 0.4 of 5. The physical model demonstrated that the posteromedial scar was subjected to lower mechanical stress and displacement. The reported technical refinements allowed pleasant arm recontouring to be achieved with acceptable scarring and a low incidence of complications. Therapeutic, IV.


Immunization and transplantation--what is new and what is coming?
Infections represent an important risk for pediatric transplant recipients. Many infections are preventable through immunization, and ongoing studies are working on increasing the number of available vaccines for these children either before or after transplantation. We examine new immunization schedules (such as pertussis vaccines in teenagers) and newly available vaccines (such as human papillomavirus vaccine), and suggest how to deliver them in pediatric transplant candidates or recipients. We also review less common vaccines (such as encephalitis vaccines), and possible vaccines of the future that could have an important clinical impact in these children, such as CMV or EBV vaccines.


Systematization of Nursing Care: seeking defining and differentiating theoretical contours.
The objective of this study was to elaborate theoretical propositions to help understanding the Systematization of Nursing Care as a distinct phenomenon of the Nursing Process. It is a reflective, theoretical study that presented two categories: "Systematization of Nursing Care: seeking differentiating contours" and "Systematization of Nursing Care: seeking defining contours". It was identified that the systematization is not concerned with guiding the professional nursing care itself, since this issue, together with the guidelines regarding the elaboration of clinical documentation resulting from the implemented nursing care, is related to the process. Despite what the Systematization of Nursing Care is, the idea is that it is a field of knowledge that, through its three pillars and constituent elements, supports the structuring of nursing services and, consequently, the organization or reorganization of professional work in nursing. It is concluded that systematization, in the light of the theoretical propositions presented here, is an area of knowledge that represents a particular way of carrying out the management of nursing services when the three pillars that compose it are considered.


Dynamic Diels-Alder reactions of maleimide-furan amphiphiles and their fluorescence ON/OFF behaviours.
The occurrence of dynamic covalent reactions only requires relatively low activation energy, which allows both the forward and reverse reactions to proceed under mild conditions. Here, we report the design and synthesis of amphiphilic maleimide-furan adducts, where hydrophobic maleimide-based and hydrophilic furan-based moieties were connected by reversible dynamic covalent bonds. The Diels-Alder addition reactions of maleimide-furan adducts are simple, efficient, clean, and reversible without catalysts and side reactions, and occur under mild conditions. Single crystal X-ray diffraction revealed that the length of the dynamic covalent bonds is 1.56 Å, which is longer and weaker than for normal covalent bonds. The cleavage and reformation process of the dynamic covalent bonds was monitored by 1H NMR and fluorescence spectroscopy. 1H NMR spectroscopy revealed that the furan moieties of these new maleimide-furan amphiphiles can be exchanged in mixing systems due to dynamic Diels-Alder reactions; thus, two new maleimide-furan compounds can be transformed into each other. The maleimide-furan amphiphiles displayed reversible fluorescence ON/OFF behaviours and interesting H-bonding driven supramolecular assembly.


Screening for sickle cell disease on dried blood: a new approach evaluated on 27,000 Belgian newborns.
Early diagnosis of sickle cell disease decreases morbidity. However, cost-effective screening programmes are not yet available. We explored the feasibility of systematic screening performed on dried blood harvested from five-day-old newborns. A total of 27,010 samples were collected in Belgian maternity units between June 2003 and February 2005, and the presence of haemoglobin (Hb) C or S in the eluted blood was examined by an enzyme-linked immunosorbent assay (ELISA) test performed with a monoclonal antibody detecting both mutated forms. As this antibody slightly cross-reacts with Hb A, better specificity is achieved if the test is performed not later than day 5. Among the 27,010 samples, 132 (0.49%) were positive. Molecular biology tests performed on dried blood from positive samples showed that 106 of these babies were heterozygotes for the Hb S mutation and three were heterozygotes for the Hb C mutation, while three newborns were SS homozygotes (0.011%). Seventeen samples (0.063%) were false-positives as we could not detect any mutation. We have developed a new immunological approach in the field of haemoglobinopathy neonatal screening. This ELISA test is cheap (0.2 euro/test or 1800 euro/detected SS homozygote) and could be centralized. Its cost-effectiveness in the whole Belgian population is comparable with that of screening for phenylketonuria or congenital adrenal hyperplasia. Further improvements should obviously be achieved in order to better discriminate heterozygotes and homozygotes, but the accessibility and the low cost of the test are relevant arguments for the screening extension in a wide range of countries, especially in Central Africa.


Structural evolution in the isotropic channel of a water-nonionic surfactant system that has a disconnected lamellar phase: a 1H NMR self-diffusion study.
We showed in a previous study that a water-nonionic surfactant system, where the surfactant is a 9:1 mixture of tetraethylene glycol monodecyl ether (C(10)E(4)) and pentaethylene glycol monodecyl ether (C(10)E(5)), forms a disconnected lamellar (L(α)) phase. Thus, the isotropic phase spans the whole concentration range from the water-rich L(1) region to the surfactant-rich L(2) region of the phase diagram. The L(1) and L(2) regions are connected via an isotropic channel that separates the two regions of the L(α) phase. In this letter, we monitored the structural evolution of the isotropic phase along a path through this isotropic channel via (1)H NMR self-diffusion measurements. We used this technique because it enables us to distinguish between discrete and bicontinuous structures by comparing the relative self-diffusion coefficients (obstruction factors) D/D(0) of the solvents (i.e. of water and surfactant in the present case). We found that the obstruction factor of water decreases whereas the obstruction factor of the surfactant increases with increasing surfactant concentration and increasing temperature. This trend is interpreted as the transition from a water-continuous L(1) region, which contains discrete micelles, to a bicontinuous structure, which may extend to very high surfactant concentrations. Although there is good evidence of bicontinuity over a broad concentration range, there is no evidence of inverse micelles or any other microstructure at the highest concentration studied in the surfactant-rich L(2) phase.


[The outcome of reactive arthritis].
Cases of reactive arthritis generally have a favourable short-term outcome, within 1 to 6 months in 50 to 70 per cent of cases. The curable nature of the disease and its short clinical course mean that the therapeutic approach should be devoid of risks. Antibiotics, which are necessary for the mucosal lesion, are ineffective in the joint involvement. Non-steroidal anti-inflammatory agents, sometimes in combination with intra-articular steroid injections, seem to be sufficient in the simple forms. In the more chronic, polyarticular forms, gold therapy would appear to be preferable to the use of drugs which act on the immune system. However, the favourable short-term course is overshadowed by the incidence of relapse (30 to 50%), which are sometimes multiple, and by the subsequent development of pelvispondylitis (30% of cases) after an average of about 6 years. Permanent or recurrent peripheral joint manifestations can be seen. The clinical course of these conditions is very similar, whatever the causative agent.


Attendance at accident and emergency departments: unnecessary or inappropriate?
The proportion of attenders at accident and emergency (A&E) departments who present 'inappropriately' with conditions which could be managed in general practice has been estimated at between 6.7 per cent and 64-89 per cent. These estimates have been based on subjective assessments by clinicians, or on an objective classification developed by the Nuffield Provincial Hospitals Trust (NPHT). This study sought to validate this classification, and to develop and validate other objective systems of classifying A&E attenders. Two novel methods were devised, one based on the ICD-9 diagnosis and one primarily on processes of care. All three techniques were validated against the pooled opinions of a sample of general practitioners (GPs). The existing NPHT classification was found to be very unreliable. The new diagnostic method was more specific but had poor sensitivity, whereas the technique based on processes of care agreed remarkably well with the sample of GPs. This method was applied retrospectively to random samples of 8877 adult self-referrals to 16 English A&E departments, and yielded an estimate that 23 per cent could have been treated in general practice. This approach provides a simple and valid retrospective method for identifying patients who were suitable for care in general practice. The method may be used to identify groups of patients who frequently attend inappropriately, to identify areas in which primary care needs are not being effectively met in general practice, and to form a basis for planning and auditing strategies to meet those needs in a more appropriate setting.


What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?
To examine incidence of treatment changes due to abnormal blood-test results and, to explore rates of treatment changes due to liver, kidney and haematological blood-test abnormalities in autoimmune rheumatic diseases (AIRD) treated with low-dose MTX or LEF. Data for people with AIRDs prescribed MTX or LEF were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of MTX or LEF in primary care. Primary outcome of interest was drug discontinuation, defined as a prescription gap of ≥90 days following an abnormal (or severely abnormal) blood-test result. Dose reduction was examined between consecutive prescriptions. Incidence rates per 1000 person-years were calculated. 15, 670 and 2,689 participants contributing 46, 571 and 4,558 person-years follow-up were included in MTX and LEF cohorts, respectively. The incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood-test was 42.24 (6.16) and 106.53 (9.42)/1000 person-years in year 1, and 22.44 (2.84) and 31.69 (4.40)/1000 person years, respectively, thereafter. The cumulative incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood tests was 1 in 24 (1 in 169), 1 in 9 (1 in 106) at 1 year; and 1 in 45 (1 in 352), 1 in 32 (1 in 227) per-year, respectively, thereafter. Raised liver enzymes were the commonest abnormality associated with drug discontinuation. MTX and LEF dose reduction incidence were comparable in year 1, however, thereafter MTX dose was reduced more often than LEF [16.60 (95% CI 13.05, 21.13) vs 8.10 (95% CI 4.97, 13.20)/1000 person-years]. MTX and LEF were discontinued for blood-test abnormalities after year 1 of treatment, however, discontinuations for severely abnormal results were uncommon.


Parallelism between avoidance-suppressing and prolactin-increasing effects of antipsychotic drugs in rats.
Temporal changes in the avoidance responses and serum prolactin levels were investigated for a 360 min period after s.c. administration of antipsychotic drugs such as chlorpromazine (2 mg/kg), prochlorperazine (2 mg/kg), haloperidol (0.035 mg/kg), droperidol (0.03 mg/kg), YM-09151-2 (0.005 mg/kg) and sulpiride (80 mg/kg) in rats. Male adult rats of the Wistar strain were trained under a continuous lever-press avoidance schedule (Sidman type) to observe avoidance-suppressing effects of the drugs. The avoidance response was suppressed after administration of chlorpromazine, prochlorperazine, haloperidol, droperidol and YM-09151-2, showing significant decrease in response rate and significant increase in shock rate when compared with those after saline administration, while it was scarcely suppressed within 150 min after sulpiride. On the other hand, serum prolactin levels were increased after administration of all the drugs used. Furthermore, parallelism between temporal changes in the avoidance responses and those in serum prolactin levels was observed after administration of the antipsychotic drugs, except for sulpiride. These results suggest that the prolactin-increasing effects of antipsychotic drugs are applicable for predicting antipsychotic efficacies in humans, excluding sulpiride therapy.


Doxycycline induces membrane expression of VE-cadherin on endothelial cells and prevents vascular hyperpermeability.
The endothelium lining blood vessels serves as a barrier against vascular hyperpermeability, and its maintenance is critical to organ health. Inflammatory mediators evoke tissue edema by disrupting the expression of membrane junctional proteins, which mediate binding between endothelial cell membranes. Endothelial cell-cell junctions form a diffusion barrier between the intravascular and interstitial space. To prevent the morbidity and mortality caused by exaggerated vascular permeability associated with pathological states (e.g., inflammatory and hypersensitivity disorders, pulmonary edema, traumatic lung injury, cerebral edema resulting from stroke, and others), it is important to develop therapeutic approaches to stabilize these interendothelial junctions. Vascular endothelial growth factor (VEGF), a potent proangiogenic cytokine, was first described as vascular permeability factor (VPF). Doxycycline, a tetracycline derivative, has been shown to inhibit angiogenesis in both humans and animal models. We now report that oral doxycycline prevents VPF/VEGF-induced vascular permeability, interleukin-2-induced pulmonary edema, and delayed-type hypersensitivity (DTH) in mice. Remarkably, doxycycline also inhibits tumor growth and tumor-associated vascular hyperpermeability. Finally, we show that doxycycline targets the adherens junction in vascular endothelial cells by inducing the total amount of VE-cadherin expression while decreasing the degree of its phosphorylation. The potential of doxycyline as a therapeutic inhibitor of vascular hyperpermeability in human clinical conditions is promising and warrants further studies.


A Longitudinal Motor Characterisation of the HdhQ111 Mouse Model of Huntington's Disease.
Huntington's disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms. Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice. An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function. A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery. The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation.


Earwig management tool: an IPM decision aid system for augmentation of European earwig populations (Dermaptera: Forficulidae) in pip fruit orchards.
A key element of integrated pest management (IPM) is the suppression of potential pest outbreaks by beneficial arthropods. The European earwig, Forficula auricularia L., is an important natural enemy of a wide range of insect pests in pip fruit orchards. However, earwig population sizes vary greatly from location to location, illustrating their sensitivity to biotic and abiotic factors, especially human interventions relating to orchard management. In order to help growers sparing and augmenting earwig populations in their pip fruit orchards, we developed a software tool that integrates a sophisticated earwig phenology model with management recommendations. The program is based on a day degree model for earwigs which is fed by temperature data collected by the pcfruit research centre. In addition, a pesticide database with known side effects of a wide range of products on the different life stages of earwigs is integrated in the system. The output gives the current status of the earwig population and management recommendations for activities critical for their survival. Hence, by consultation of this user-friendly software fruit growers can predict the earwig development in the field at any time, and organize the timing of orchard management actions taking into account the presence of (sensitive) life stages of the earwig life cycle. Doing so, negative effects specific orchard management actions, such as badly timed spray applications and soil tillage, can be avoided.


Signal, bias, and the role of transcriptome assembly quality in phylogenomic inference.
Phylogenomic approaches have great power to reconstruct evolutionary histories, however they rely on multi-step processes in which each stage has the potential to affect the accuracy of the final result. Many studies have empirically tested and established methodology for resolving robust phylogenies, including selecting appropriate evolutionary models, identifying orthologs, or isolating partitions with strong phylogenetic signal. However, few have investigated errors that may be initiated at earlier stages of the analysis. Biases introduced during the generation of the phylogenomic dataset itself could produce downstream effects on analyses of evolutionary history. Transcriptomes are widely used in phylogenomics studies, though there is little understanding of how a poor-quality assembly of these datasets could impact the accuracy of phylogenomic hypotheses. Here we examined how transcriptome assembly quality affects phylogenomic inferences by creating independent datasets from the same input data representing high-quality and low-quality transcriptome assembly outcomes. By studying the performance of phylogenomic datasets derived from alternative high- and low-quality assembly inputs in a controlled experiment, we show that high-quality transcriptomes produce richer phylogenomic datasets with a greater number of unique partitions than low-quality assemblies. High-quality assemblies also give rise to partitions that have lower alignment ambiguity and less compositional bias. In addition, high-quality partitions hold stronger phylogenetic signal than their low-quality transcriptome assembly counterparts in both concatenation- and coalescent-based analyses. Our findings demonstrate the importance of transcriptome assembly quality in phylogenomic analyses and suggest that a portion of the uncertainty observed in such studies could be alleviated at the assembly stage.


Role of MGMT as biomarker in colorectal cancer.
O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.


Wide-open flaps are key to urease activity.
Substrate ingress and product egress from the active site of urease is tightly controlled by an active-site flap. Molecular dynamics simulations of urease have revealed a previously unobserved wide-open flap state that, unlike the well-characterized closed and open states, allows ready access to the metal cluster in the active site. This state is easily reached from the open state via low free energy barriers. Additionally, we have found that even when the flap is closed, a region of the binding pocket is solvent-exposed, leading to the hypothesis that it may act as a substrate/product reservoir. The newly identified wide-open state offers further opportunities for small-molecule drug discovery by defining a more extensive active-site pocket than has been previously described.


Duodenum-sparing resection of the pancreatic head combined with pancreatogastroanastomosis in the treatment of chronic pancreatitis--surgical technique.
Chronic pancreatitis is defined as progressively developing disease which reduces exocrine parenchyma and decreasing exocrine capacity of the pancreas. The disease is commonly manifested by recurrent attacks of severe and often incapacitating upper abdominal and back pain. The goal of surgical therapy is pain relief and unblocking of the stenosis of the common bile duct and duodenum. Our method of solving this problem is a duodenum sparing resection of the pancreatic head followed by simple reconstruction of the gastrointestinal tract using pancreatogastroanastomosis. All unnecessary anastomoses are thus reduced and the risk of anastomotic leak is minimized. The substantial advantage of this operation is the removal of the pancreatic head where the source of symptoms related to chronic pancreatitis is localized.


Central 6-OHDA affects both open-field exploratory behaviour and the development of hypertension in SHR.
To investigate the possible relation between changes in behaviour and the development of hypertension in the spontaneously hypertensive rat (SHR), the effect of intracerebroventricular (ICV) administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) on blood pressure and spontaneous behaviour was studied. In addition to an attenuation of the rise in blood pressure in SHR, 6-OHDA induced a marked decrease in rearing activity in the open field towards levels found in WKY. Other parameters were either not changed (stereotyped sniffing) or influenced in a comparable way in SHR and WKY (increase in locomotion). These results suggest that ICV 6-OHDA may simultaneously affect the development of hypertension and certain components of the changed behaviour of SHR. The exact relation between the two phenomena awaits further investigation.


Exploring insights for virulent gene inhibition of multidrug resistant Salmonella typhi, Vibrio cholerae, and Staphylococcus areus by potential phytoligands via in silico screening.
In our recent studies on prevalence of multidrug resistant pathogens in Byramangala reservoir, Karnataka, India, we identified Salmonella typhi, Staphylococcus aureus, and Vibrio cholerae which had acquired multiple drug resistance (MDR) and emerged as superbugs. Hence, there is a pressing demand to identify alternative therapeutic remedies. Our study focused on the screening of herbal leads by structure-based virtual screening. The virulent gene products of these pathogens towards Kanamycin(aph), Trimethoprim(dfrA1), Methicillin (mecI), and Vancomycin (vanH) were identified as the probable drug targets and their 3D structures were predicted by homology modeling. The predicted models showed good stereochemical validity. By extensive literature survey, we selected 58 phytoligands and their drug likeliness and pharmacokinetic properties were computationally predicted. The inhibitory properties of these ligands against drug targets were studied by molecular docking. Our studies revealed that Baicalein from S. baicalensis (baikal skullcap) and Luteolin from Taraxacum officinale (dandelion) were identified as potential inhibitors against aph of S. typhi. Resveratrol from Vitis vinifera (grape vine) and Wogonin from S. baicalensis were identified as potential inhibitors against dfrA1 of S. typhi. Herniarin from Herniaria glabra (rupture worts) and Pyrocide from Daucus carota (Carrot) were identified as the best leads against dfrA1 of V. cholerae. Taraxacin of T. officinale (weber) and Luteolin were identified as potential inhibitors against Mec1. Apigenin from Coffee arabica (coffee) and Luteolin were identified as the best leads against vanH of S. aureus. Our findings pave crucial insights for exploring alternative therapeutics against MDR pathogens.


Expression of preproenkephalin A gene and presence of Met-enkephalin in dorsal root ganglia of the adult rat.
The expression of the preproenkephalin A gene was investigated in adult rat dorsal root ganglia (DRG). A radioimmunoassayable Met-enkephalin (ME)-like material was detected in 0.1 M HCl extracts of rat DRG, representing approximately 60 pg of ME equivalents/mg of protein. Chromatographic analyses indicated that the major component of the ME-like material coeluted with authentic ME. In northern blot experiments on total RNA extracted from DRG, a cDNA probe corresponding to the entire coding region of rat preproenkephalin A mRNA yielded a single band of the expected size for this mRNA, i.e., 1.5 kb. Polymerase chain reaction (PCR) experiments were carried out with DRG, striatum, and liver cDNAs using two primers flanking the 1,371-1,771 base region of the preproenkephalin A gene. Thirty PCR cycles performed on both striatum and DRG cDNAs generated a single band of 400 bp, as expected, whereas only trace amounts of this product were detectable using liver cDNAs. Nucleotide sequencing of the PCR product obtained with DRG cDNAs revealed a 100% homology with the 1,371-1,771 sequence of the preproenkephalin A gene. In situ hybridization with a cRNA probe showed that about 3.5% of DRG cells expressed the preproenkephalin A transcript. However, most of these cells probably did not process proenkephalin to enkephalins, as thorough immunohistochemical investigations with anti-ME antibodies allowed the detection of only one in approximately 6,000 cells (in 30 sections of DRG) that exhibited ME-like immunoreactivity. Cells expressing preproenkephalin A mRNA were intermediate-sized neurons, suggesting that primary afferent ME-containing fibers belong to the A category and may participate in a local (spinal) inhibitory control of nociception.


[In vitro synthesis of tyrosine hydroxylase].
RNA from PC 12 cells was translated in a cell-free system and the peptides synthesized in vitro were analyzed by immunoprecipitation with an anti-T.H. serum raised in Rabbit. Analysis of the immunoprecipitate on a SDS-polyacrylamide gel reveals a major band with a molecular weight of 62000 dalton. A protein of the same molecular weight was also precipitated from a PC12 cell lysate. This molecular weight of 62000 dalton corresponds to the reported for tyrosine hydroxylase purified from PC12 cells.


Quercetin suppresses the tumorigenesis of oral squamous cell carcinoma by regulating microRNA-22/WNT1/β-catenin axis.
Quercetin has potential pharmacological values in various carcinomas including oral squamous cell carcinoma (OSCC). Moreover, the anti-tumor effect of quercetin is correlated with WNT/β-catenin pathway and miRNA dysregulation. In the present study, we aimed to further investigate whether quercetin can exert its anti-tumor function by regulating miR-22 together with miR-22 downstream pathway WNT1/β-catenin in OSCC. The results of Cell Counting Kit-8 (CCK-8) and flow cytometry analyses showed that quercetin treatment and miR-22 overexpression resulted in the reduction of cell viability and the increase of cell apoptotic rate in OSCC. WNT1 was a target of miR-22, which was confirmed by bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays. RT-qPCR assay showed that quercetin promoted miR-22 expression and suppressed WNT1 and β-catenin expression in OSCC cells, whereas this effect was abrogated by miR-22 inhibitor. Moreover, miR-22 depletion weakened quercetin-mediated viability inhibition and apoptosis increase in OSCC cells. Quercetin inhibited the growth of OSCC xenograft tumors by inducing miR-22 expression and repressing WNT1/β-catenin pathway in vivo. Taken together, quercetin hampered OSCC tumorigenesis by regulating miR-22/WNT1/β-catenin pathway in OSCC, providing a deep insight into the molecular targets of quercetin in the treatment of OSCC.


Thermal pre-treatment in the OSL dating of quartz: is it necessary?
Thermal treatment before optically stimulated luminescence (OSL) measurement is an important step in all widely accepted OSL dating procedures used with quartz. This is a major constraint on the design of a portable luminescence instrument for estimating ages in the field. Preliminary experiments show that using a standard dating protocol without heating caused a 30-50% underestimation of equivalent dose. This underestimate arises mainly from OSL derived from the 110 degrees C thermoluminescence (TL) trap; because of the thermal instability of this trap, this OSL contribution is only present in unheated laboratory-regenerated signals, but not in the natural signal. An alternative to thermal pre-treatment is investigated, based on the mathematical separation of the stable dosimetry OSL signal from the total OSL; the latter is the sum of signals from several traps, including the 110 degrees C TL trap. Our results show consistency with dose estimates obtained using a standard measurement protocol including pre-heating.


Cryptogenic organizing pneumonia associated with radiation: A report of two cases.
Cryptogenic organizing pneumonia (COP) following radiotherapy is occasionally diagnosed as radiation pneumonitis or bacterial pneumonia. The current study presents two cases of COP following radiotherapy: A 48-year-old premenopausal female with breast cancer and an 84-year-old male with non-small cell lung cancer. In the cases of breast cancer and lung cancer, patients were first diagnosed with bacterial pneumonia and radiation pneumonitis, respectively. In the two cases, computed tomography disclosed the migration of ground glass shadows, which were finally resolved without any fibrotic changes. The two cases were finally diagnosed as COP associated with radiotherapy. When an infiltrating shadow is present outside of the irradiated field, COP must be included in the differential diagnosis.


European medical device regulation: a new era?
By the spring of 2005, the European Commission hopes to present the first draft of the revisions to the Medical Device Directive to the European Council and Parliament. However, these revisions represent only part of the changing European regulatory scenario. This article discusses a tangible shift in European medical device regulatory policy and some actions that companies can take to understand and prepare for these policies.


Novel Sol-Gel Synthesis of TiO2 Spherical Porous Nanoparticles Assemblies with Photocatalytic Activity.
For this study, the synthesis of TiO2 nanomaterials was performed via a novel sol-gel method employing titanium butoxide as a metal precursor, Pluronic F127 as a templating agent, toluene as a swelling agent, and acidic water or ethanol as the reaction solvents. The method was designed by tailoring certain reaction parameters, such as the sequence of toluene addition, magnetic stirring, the type of reaction solvent, and the calcination conditions. Analysis of the specific surface area and porosity was carried out via N2 physisorption, whereas the morphological features of the solids were investigated via transmission electron microscopy. The crystalline structure of both the dried powders and the calcined materials was evaluated using X-ray diffraction analysis. It transpired that the different phase compositions of the solids are related to the specific synthesis medium employed. Under the adopted reaction conditions, ethanol, which was used as a reaction solvent, promoted the local arrangement of dispersed anatase particles, the specific arrangement of which does not lead to rutile transformation. Conversely, the use of water alone supported high-particle packing, evolving into a rutile phase. The photodegradation of Rhodamine B was used as a target reaction for testing the photocatalytic activity of the selected samples.


Associating life stages and sexes of Nearctic Polycentropus Curtis, 1835 (Trichoptera: Polycentropodidae) using mitochondrial DNA barcoding.
Alpha taxonomy of caddisflies (order Trichoptera) is based primarily on male genital morphology. As such, associations of adult females and other life stages typically require conclusive association with the species' identifiable male. The aim of this study was to use molecular methods to associate females and larvae of Polycentropus species represented in the Nearctic. Analysis of mtCOI sequences using distance- and tree-based methods resulted in the association of larvae for 14 species of Polycentropus (P. alabamensis Hamilton, Harris & Lago, 1990, P. blicklei Ross & Yamamoto 1965, P. carlsoni Morse 1971, P. carolinensis Banks 1905, P. colei Ross 1941, P. confusus Hagen 1861, P. denningi Smith 1962, P. elarus Ross 1944, P. gertschi Denning 1950, Polycentropus halidus Milne 1936, P. maculatus Banks 1908, P. pentus Ross 1941, P. rickeri Yamamoto 1966, and P. variegatus Banks 1900) and females for 2 species (P. carolinensis and P. chelatus Ross & Yamamoto 1965). Searches for, and descriptions of, diagnostic morphological characters for these previously unidentifiable life forms are now possible. The identity of the larva of P. centralis Banks, 1914 is confirmed and some interesting phylogenetic relationships and a possible cryptic species and potential synonyms are implied in the results. Targets for future immature- and female-male associations are discussed along with a preliminary assessment of morphological differences among larvae.


Single cell trapping in larger microwells capable of supporting cell spreading and proliferation.
Conventional cell trapping methods using microwells with small dimensions (10-20 μm) are useful for examining the instantaneous cell response to reagents; however, such wells have insufficient space for longer duration screening tests that require observation of cell attachment and division. Here we describe a flow method that enables single cell trapping in microwells with dimensions of 50 μm, a size sufficient to allow attachment and division of captured cells. Among various geometries tested, triangular microwells were found to be most efficient for single cell trapping while providing ample space for cells to grow and spread. An important trapping mechanism is the formation of fluid streamlines inside, rather than over, the microwells. A strong flow recirculation occurs in the triangular microwell so that it efficiently catches cells. Once a cell is captured, the cell presence in the microwell changes the flow pattern, thereby preventing trapping of other cells. About 62% of microwells were filled with single cells after a 20 min loading procedure. Human prostate cancer cells (PC3) were used for validation of our system.


Diagnosis, Treatment, and Management of Otitis Media with Artificial Intelligence.
A common infectious disease, otitis media (OM) has a low rate of early diagnosis, which significantly increases the difficulty of treating the disease and the likelihood of serious complications developing including hearing loss, speech impairment, and even intracranial infection. Several areas of healthcare have shown great promise in the application of artificial intelligence (AI) systems, such as the accurate detection of diseases, the automated interpretation of images, and the prediction of patient outcomes. Several articles have reported some machine learning (ML) algorithms such as ResNet, InceptionV3 and Unet, were applied to the diagnosis of OM successfully. The use of these techniques in the OM is still in its infancy, but their potential is enormous. We present in this review important concepts related to ML and AI, describe how these technologies are currently being applied to diagnosing, treating, and managing OM, and discuss the challenges associated with developing AI-assisted OM technologies in the future.


[Blood immunoglobulin deficiencies during bronchial asthma in the adult].
The study of serous immunoglobulins of 500 asthmatic patients enabled the authors to discover a deficit in one of the Ig in 93 cases (18.6%), mainly in cases of intrinsic allergic asthma with an important or dominant infectious character, or microbial asthma. It concerned partial shortages of usually only one Ig in each patient, mostly the IgG. The importance of these deficits is discussed, particularly in the origin of bacterial sensitivity of these asthmas and in the genesis of atopy. The problem of IgG reagins is also discussed. Practical deductions drawn form these findings are envisaged.


Mechanism of deletion of endothelial cells during regression of the corpus luteum.
Endothelial cells are deleted rapidly, and in large numbers, during cyclical regression of the corpus luteum of the guinea pig. This paper reports a study of the mechanisms, structural and causal, by which this deletion occurs. Corpora lutea from guinea pigs were examined by transmission electron microscopy on day 9 (functional stage) and day 16 (regressing) of the estrous cycle. Corpora lutea were also studied at 1, 3, 12, 24, and 48 hours after administration of a synthetic luteolytic substance (cloprostenol), and after temporary occlusion of the ovarian blood vessels for 15, 30, 60, or 120 minutes. Early signs of endothelial cell degeneration included protrusion of some individual cells into capillary lumina and the formation of adherens junctions across the lumen. Intermediate stages of degeneration included nuclear and cytoplasmic condensation and cellular and nuclear lobation or fragmentation in cells either protruding into, or lying within, the lumen. Terminal changes included loss of plasma membrane integrity and cytoplasmic density, together with disruption of cell organelles. Some degenerate endothelial cells were engulfed by viable endothelial cells. Macrophages were not seen to be involved in removal of dead endothelial cells, and integrity of the walls of capillaries was maintained while individual endothelial cells were deleted. Experimental findings were consistent with the hypothesis that cessation or reduction of flow of blood along capillaries plays an etiologic rule in endothelial cell deletion.


STEP (Statistical Test of Equivalent Pathways) analysis: a mass spectrometric method for carbohydrates and peptides.
We have recently developed a new mass spectrometry method, the STEP (statistical test of equivalent pathways) analysis that uses ion abundances in two tandem mass spectrometry experiments to obtain genealogy information about product ions present in mass spectra. The method requires minimal sample, and it can be performed using a conventional quadrupole ion trap mass spectrometer. To obtain genealogy information, STEP ratios are calculated by comparing the relative abundances of product ions in two MS/MS experiments. These ratios are directly related to the origin of the product ions. Product ions that result directly from the precursor ion always have STEP ratios that are </=1. Ions that result from secondary fragmentation pathways have STEP ratios that are significantly larger than the primary ions, based on a Q test of statistical significance. Consequently, the type (primary or secondary) of all the product ions in an MS/MS experiment can easily be identified in this analysis. The STEP method is applied herein to peptides and carbohydrates, and the STEP results are consistent with validation data for 95% of the ions in this study. This new method has many applications in carbohydrate and peptide analysis. It can be used to support mechanistic studies of peptide fragmentation, and it is useful for discriminating among various isomeric carbohydrates, without the need for reference standards. Several examples are presented to demonstrate the reliability of this method, and an example showing how the method benefits carbohydrate sequencing is also provided.


Solid state coordination chemistry: one-, two-, and three-dimensional materials constructed from molybdophosphonate subunits linked through binuclear copper tetra-2-pyridylpyrazine groups.
The hydrothermal reactions of MoO(3), an appropriate Cu(II) source, tetra-2-pyridylpyrazine (tpypyz), and phosphoric acid and/or an organophosphonate yielded a series of organic-inorganic hybrid materials of the copper-molybdophosphonate family. A common feature of the structures is the entrainment within the extended architectures of chemically robust [Mo(5)O(15)(O(3)PR)(2)](4)(-) clusters as molecular building blocks. The cluster is a characteristic feature of the one-dimensional materials [[Cu(2)(tpypyz)(H(2)O)(3)]Mo(5)O(15)(HPO(4))(O(3)PCH(2)CO(2)H)].H(2)O (1.H(2)O) and [[Cu(2)(tpypyz)(H(2)O)]Mo(5)O(15)(O(3)PC(6)H(5))(2)].2H(2)O (2.2H(2)O), the two-dimensional network [[Cu(2)(tpypyz)(H(2)O)(3)]Mo(5)O(15)(HPO(4))(2)].2H(2)O (5.2H(2)O) and the three-dimensional frameworks [[Cu(2)(tpypyz)(H(2)O)(2)]Mo(5)O(15)[O(3)P(CH(2))(n)()PO(3)]].xH(2)O [n = 3, x = 2.25 (6.2.25H(2)O); n = 4, x = 0.33 (7.0.33H(2)O)]. In the case of methylenediphosphonate as the phosphorus component, the unique chelating nature of the ligand precludes formation of the pentamolybdate core, resulting in the chain structures [[Cu(2)(tpypyz)(H(2)O)]Mo(3)O(8) (HO(3)PCH(2)PO(3))(2)].8H(2)O (3.8H(2)O) and [[Cu(2)(tpypyz)(H(2)O)](2)(Mo(3)O(8))(2)(O(3)PCH(2)PO(3))(3)].16.9H(2)O (4.16.9H(2)O). For structures 1-7, the secondary metal-ligand building block is the binuclear [Cu(2)(tpypyz)(H(2)O)(x)](4+) cluster. There is considerable structural versatility as a result of the variability in the number of attachment sites at the phosphomolybdate clusters, the coordination geometry of the Cu(II), which may be four-, five-, or six-coordinate, the extent of aqua ligation, and the participation of phosphate oxygen atoms as well as molybdate oxo groups in bonding to the copper sites. Crystal data: 1.H(2)O, C(26)H(28)N(6)Cu(2)Mo(5)O(28)P(2), monoclinic C2/c, a = 42.497(2) A, b = 10.7421(4) A, c = 20.5617(8) A, beta = 117.178(1) degrees, V = 8350.1(5) A(3), Z = 8; 2.2H(2)O, C(36)H(32)N(6)Cu(2)Mo(5)O(24)P(2), monoclinic P2(1)/c, a = 11.2478(7) A, b = 19.513(1) A, c = 21.063(1) A, beta = 93.608(1) degrees, V = 4613.7(5) A(3), Z = 4; 3.8H(2)O, C(26)H(40)N(6)Cu(2)Mo(3)O(29)P(4), monoclinic C2/c, a = 32.580(2) A, b = 17.8676(9) A, c = 15.9612(8) A, beta = 104.430(1) degrees, V = 8993.3(8) A(3), Z = 8; 4.16.9H(2)O, C(51)H(71.75)Cu(4)Mo(6)N(12)O(51)P(6), monoclinic P2(1)/c, a = 27.929(3) A, b = 12.892(2) A, c = 22.763(3) A, beta = 90.367(2) degrees, V = 8195.7(2) A(3), Z = 4;( )()5.2H(2)O, C(24)H(28)N(6)Cu(2)Mo(5)O(28)P(2), monoclinic P2(1)/n, a = 11.3222(4) A, b = 18.7673(7) A, c = 19.4124(7) A, beta = 98.819(1) degrees, V = 4076.1(3) A(3), Z = 4; 6.2.25H(2)O, C(27)H(28.5)N(6)Cu(2)Mo(5)O(24.25)P(2), monoclinic C2/c, a = 12.8366(5) A, b = 18.4221(8) A, c = 34.326(1) A, beta = 100.546(1) degrees, V = 7980.1(6) A(3), Z = 8; 7.(1)/(3)H(2)O, C(28)H(28.7)N(6)Cu(2)Mo(5)O(23.3)P(2), monoclinic C2/c, a = 12.577(1) A, b = 18.336(1) A, c = 36.476(3) A, beta = 91.929(2) degrees, V = 8407.3 A(3), Z = 8.


NMR and theoretical study on the coordination and solution structures of the interaction between diperoxovanadate complexes and histidine-like ligands.
To simulate the types of coordination and solution structures of the active site of haloperoxidases, the interaction systems between diperoxovanadate complexes [OV(O2)2L]n- (n = 1 or 3, L = oxalate or H2O) and a series of histidine-like ligands in solution have been studied by using 1D multinuclear (1H, 13C, and 51V) NMR, 2D diffusion ordered spectroscopy, and variable-temperature NMR in 0.15 mol/L NaCl ionic medium, representing the physiological conditions of human blood. Some direct NMR data are given for the first time. The reactivity among the histidine-like ligands is imidazole > 2-methylimidazole > carnosine approximately 4-methylimidazole > histidine. Competitive coordination interactions result in a series of new peroxovanadate species [OV(O2)2L']- (L' = histidine-like ligands). When the ligands are 4-methylimidazole, histidine, and carnosine, a pair of isomers have been observed, which are attributed to different types of coordination between vanadium atom and ligands. The results of density functional theory calculations provided a reasonable explanation on the relative reactivity of the histidine-like ligands and the molar ratios of isomers. Theoretical results signify the importance of the solvation effect for the reactivity and stability of the interaction systems.


Countermeasures for Urban Traffic Congestion in China from the Perspective of System Dynamics.
In recent years, urban traffic congestion has seriously affected the healthy development of urbanization in China. And many measures to combat congestion have had little effect . The purpose of this paper is to find out the most reasonable and sustainable measures to control traffic congestion . Based on the theory of system dynamics, this study constructs a model of the formation mechanism of urban traffic congestion in China, and analyzes the thinking error of the traditional strategy of "building roads to eliminate traffic congestion" This study includes the current policy measures to control traffic congestion in the system dynamics model and analyzes the influence of each measure on the formation mechanism of urban traffic congestion. Then, it critiques the unsustainability of rigid policies, such as the vehicle number limit and the "similar road building to control traffic congestion" policies. This study reveals that of the five policies adopted by the government to alleviate traffic congestion, and come to the conclusion: the "sparse block collocation" policy is the most sustainable and fundamental congestion control measure. To achieve efficient traffic congestion control and support the healthy development of urbanization in China in the future, the government should increase the balance of infrastructure investment to improve the slow environment of public transport, adhere to public transport-oriented land development policies, raise the cost of motor vehicle travel, and promote urban traffic.


Parameters predicting response to alpha-interferon treatment in chronic hepatitis C.
Sustained response to alpha-interferon treatment for chronic hepatitis C is seen in only 25% of cases. Therefore, it is desirable to define pretreatment factors predicting responders. Forty-nine patients with chronic hepatitis C were treated with a standard alpha-interferon regimen (3 x 3 MU s.c./week). Demographic, biochemical and immunological parameters, and HCV genotypes were obtained prior to initiation of treatment and evaluated for their value in predicting response to alpha-interferon therapy. Response, as defined by normalization of ALT, was 71% during interferon therapy and sustained response after discontinuation of interferon 24.5%. Patients infected with HCV-genotype 1b had significantly more often "community-acquired" disease. Their outcome was worse with a response rate of 44% during therapy and a sustained response of 12.5%, as compared to 87% and 27% respectively in patients infected with genotypes other than 1b. On multivariate analysis, absence of cirrhosis, HCV-genotype other than 1b, higher ALT levels and higher numbers of CD8 positive liver infiltrates were found to be predictors of response during alpha-interferon therapy. Response to alpha-interferon therapy seems to be influenced both by viral virulence factors and by the intensity of the host immune response to HCV.


Modification of experimental colon carcinogenesis by dietary fibers.
The literature concerning the effect of individual dietary fibers on the experimental induction of colorectal cancer was reviewed. It has become increasingly apparent that the effect of dietary fibers on colon carcinogenesis depends on many factors, including the type and amount of fiber; the other dietary components, particularly fat; animal species, strain, and sex; and the type of carcinogen and its dose and route of administration. Despite such variations in design, most experiments with wheat bran and cellulose have shown evidence of a significant protective effect. In contrast, numerous other fiber supplements have been shown to enhance tumor development. These include pectin, corn bran, undegraded carageenan, agar, Metamucil, and alfalfa. Possible mechanisms by which fibers may inhibit colon tumorigenesis include dilution and adsorption of any carcinogens or promoters contained within the intestinal lumen and faster transit time and therefore less opportunity for carcinogen/promoter interaction with the intestinal epithelium. Modulation of colonic microbial metabolic activity by dietary fibers may also be important in the activation and detoxification of carcinogens and promoters. Dietary fibers produce structural and functional changes in the intestinal epithelium and modify rates of cell proliferation changes in the intestinal epithelium and modify rates of cell proliferation and migration. Evidence suggests that if this stimulus to cell proliferation occurs during the stage of initiation, it may lead to enhancement of the carcinogenic process. Dietary fibers bind not only carcinogens, bile acids, and other potentially toxic agents but also essential nutrients that themselves can modify the carcinogenic process. Fermentation of fibers within the large bowel results in production of volatile fatty acids, which in vitro have been shown to be antineoplastic. Fermentation also produces a lower luminal pH, which in turn affects colonic microbial populations and their metabolic activities. The presence of lignans in higher plants and their bacterial synthesis from precursors present in fiber-rich foods provide an additional source of antineoplastic agents, whose relative importance in colon carcinogenesis is unknown. Because dietary fibers differ in their physiochemical properties, it has been difficult to identify a single mechanism by which fibers prevent or inhibit colon carcinogenesis. Clearly, more investigation is needed regarding the mechanism(s) by which certain fibers inhibit while others enhance experimental colon carcinogenesis.


[Historical analysis of ABEn's Newsletter: changes and transformations in the XXI Century].
This is an descriptive-exploratory and interpretative study that presents and criticizes matters of 19 issues of ABEn's Newsletter published in the beginning of XXI Century, under the nursing student's view. The study aimed at identifying, quantifying and analyzing the content of this publication that is published since 1958, whose content offers information of general and political interest to guide Nursing routes. The analysis allowed to observe that the periodical had jumped in quality since the beginning of 2002, and that prevalent authorship is of membership directors of National ABEn, while predominant thematic are related to health policies and nursing education.


MOLECULAR AND GEOLOGIC EVIDENCE OF SHARED HISTORY BETWEEN HERMIT CRABS AND THE SYMBIOTIC GENUS HYDRACTINIA.
The paleobiogeographic histories of three North Atlantic hermit crab lineages were compared with a single-copy DNA-DNA hybridization phylogeny of their symbiotic hydroid genus Hydractinia to test hypotheses of shared history between these host and symbiont lineages. A survey of the geologic literature suggests that two vicariance events in the Quaternary are responsible for existing range disjunctions of the host hermit crab lineages. The Hydractinia phylogeny revealed two distinct clades, one with a primarily northern and the other with a primarily southern distribution. In two of three cases, hydroids associated with closely related hermits on both sides of the range disjunction appear as sister taxa in the phylogeny. A linear scaling between a measure of hydroid sequence divergence and independent geologic estimates of the timing of the vicariant events believed to have established the hermit crab range disjunctions is consistent with the claim of temporal coincidence of cladogenic and vicariance events. These findings provide evidence for shared history of symbiotic associations in two of the three cases.


Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement.
Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis. To determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing. We detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype-phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purposes.


[Patient Helicobacter pylori infectivity after gastric resection].
The article is devoted to investigation of the Helicobacter pylori (HP) infection in 14 patients after resection of the stomach for ulcers of the gastroduodenal zone. Different methods were used for the assessment of the state of the gastric stump and gastroenteric anastomosis in the postoperative period. In most cases different degree of inflammatory alterations of the gastric mucosa were detected. In 2 cases (14.3%) peptic ulcers of the anastomosis developed. Changes to the gastric stump of 11 patients were associated with the HP infection which involved the mucosa of the anastomosed intestine in 8 patients. The data obtained point to possible participation of HP pathogenesis of the alterations detected after the stomach resection. The question of the expediency of a specific antibacterial therapy in the postoperative period and in treatment of certain kinds of postgastroresectional syndromes is raised.


Bacteriuria of pregnancy--an update on significance, diagnosis and management.
Bacteriuria of pregnancy is a common condition which is thought to be associated with serious sequelae in mother and fetus. A programme of screening, treatment and follow-up is likely to be cost-effective, but will depend on local prevalences of bacteriuria and pyelonephritis. If treatment is undertaken, nitrofurantoin and cephalexin are both safe and effective and have resistance rates of below 10%. Amoxycillin is also safe, but resistance rates in Escherichia coli are about 40%. A 7 day course of treatment remains advisable.


Etiopathogenesis of otosclerosis: a hypothesis.
It is hypothesized that otosclerosis is an autoimmune disease in response to native type II collagens of cartilage rests associated with globular ossei in the endochondral layer of the otic capsule. To support this hypothesis animal experimental data and human antibody data are shown.


The use of heuristics during route planning by expert and novice orienteers.
Expert orienteers have reported using two heuristics when planning routes to points in the environment that must be located, known as 'controls'. These heuristics constitute attending to the start first and subsequently planning forward to a given control, and attending to the control first and planning backwards to the start. The aim of this study was to establish which heuristic experts use predominantly and whether novices' use of these heuristics differs from that of experts. Two methods for tracing attention were used while 20 expert and 20 novice orienteers planned routes in the laboratory. The results were used to infer the use of heuristics. The orienteers were also interviewed about planning. We found that, when planning, experts generally attend to the control first and novices to the start first. There was also some evidence that novices work forwards from the start to the control and that experts work backwards from the control to the start. From the interviews, it would appear that experts regard the location of the control as the crux of the problem and prioritize this area during planning. These results have implications for an understanding of expertise and problem-solving in sport.


Using a Dedicated Extremity MRI Scanner for Depicting Anatomic Structures of Common Wrist Pathologies: A Pilot Comparison with a 3-Tesla MRI Scanner.
Background This pilot study explored the value of a dedicated extremity magnetic resonance imaging (MRI) scanner by focusing on the qualitative depiction of important wrist structures in common wrist pathologies, the overall image quality, artifacts, and participant experience in undergoing the examinations. Methods Images of the right wrist of 10 healthy adult volunteers were acquired with a 0.31-Tesla (T) dedicated extremity MRI and a 3-T MRI system, using a dedicated wrist coil. Images were separately evaluated by three radiologists. Paired images were randomized and graded for the visibility of anatomical details, including the triangular fibrocartilage complex (TFCC; central disc, meniscus homolog, and ulnar attachment), carpal ligaments (scapholunate [SL] and lunotriquetral [LT] ligaments), intercarpal cartilage, and median and ulnar nerves. Mean values and standard deviations of evaluation results were calculated for each sequence. Participants' experience in undergoing the examination in both MRI scanners was explored using a questionnaire. Results The mean values of anatomic structures and overall image quality were significantly in favor of the 3-T MRI scanner, compared with the dedicated extremity MRI scanner. With respect to patient satisfaction in undergoing the examination, the overall trend suggested that patients were more in favor of the dedicated extremity MRI scanner. Conclusion For defining the real clinical value of the dedicated MRI scanner in the treatment of hand and wrist pathology, studies focused on pathologies are needed, which is certainly warranted, considering the important benefits of these devices including lower costs and higher accessibility for both patients and health care providers.


Atypical decubital fibroplasia: a series of three cases.
We report three cases of atypical decubital fibroplasia (ADF), a benign, reactive pathologic process that develops in the skin and subcutaneous tissue of immobilized or debilitated patients. Two patients were immobilized, one wheelchair bound, and one bedridden. The third patient frequently lay over the affected area. Two were male, one female, ages 49, 66, and 89 (mean 68 years old). Each patient presented with a subcutaneous mass, one with focal surface ulceration, present for 5 months, 6 months, and 12 months (mean 7.7 months). The locations included back, lateral thigh (over greater trochanter), and lateral chest wall. No other lesions were present, and none had recurrences. Histologically, atypical decubital fibroplasia is characterized principally by dermal and subcutaneous tissue involvement with fibrinoid necrosis, reactive fibrosis, and focal myxoid change with surrounding more cellular zones of prominent reactive neovascularization including granulation tissue and ectatic vessels with reactive atypical fibroblasts and fat necrosis. Other findings include hyalinization of vessel walls, fibrin thrombi, red blood cell extravasation, hemosiderin deposition, and acute and chronic inflammation. Although the changes are predominantly deep, involving the dermis, subcutaneous tissue and skeletal muscle, the overlying epidermis may ulcerate. Recognition of atypical decubital fibroplasia is of paramount importance, for it may be misinterpreted as a sarcoma, both clinically and histologically.


State-of-the-Art Genetic Modalities to Engineer Cyanobacteria for Sustainable Biosynthesis of Biofuel and Fine-Chemicals to Meet Bio-Economy Challenges.
In recent years, metabolic engineering of microorganisms has attained much research interest to produce biofuels and industrially pertinent chemicals. Owing to the relatively fast growth rate, genetic malleability, and carbon neutral production process, cyanobacteria has been recognized as a specialized microorganism with a significant biotechnological perspective. Metabolically engineering cyanobacterial strains have shown great potential for the photosynthetic production of an array of valuable native or non-native chemicals and metabolites with profound agricultural and pharmaceutical significance using CO2 as a building block. In recent years, substantial improvements in developing and introducing novel and efficient genetic tools such as genome-scale modeling, high throughput omics analyses, synthetic/system biology tools, metabolic flux analysis and clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease (CRISPR/cas) systems have been made for engineering cyanobacterial strains. Use of these tools and technologies has led to a greater understanding of the host metabolism, as well as endogenous and heterologous carbon regulation mechanisms which consequently results in the expansion of maximum productive ability and biochemical diversity. This review summarizes recent advances in engineering cyanobacteria to produce biofuel and industrially relevant fine chemicals of high interest. Moreover, the development and applications of cutting-edge toolboxes such as the CRISPR-cas9 system, synthetic biology, high-throughput "omics", and metabolic flux analysis to engineer cyanobacteria for large-scale cultivation are also discussed.


Marketplace Clinics Complementing Diabetes Care for Urban Residing American Indians.
For several decades, the Minneapolis American Indian population has experienced limited health care access and threefold diabetes health disparity. As part of an urban health initiative, the marketplace clinics located in nearby CVS, Target, and Supervalu stores committed financial support, providers, certified educators, and pharmacy staff for a community-based diabetes support group. To measure the extent to which collaborating marketplace clinics and the community-based support group expanded diabetes care and provided self-management education for this largely urban Indian neighborhood. A controlled quasi-experimental study and 3-years retrospective analysis of secondary data were used to test whether the Minneapolis marketplace clinics and the community diabetes support group participants (n = 48) had improved diabetes health outcomes relative to the comparison group (n = 87). The marketplace complemented intervention group employed motivational interviewing and the patient activation measure (PAM®) in coaching diabetes self-care and behavioral modification. The federally funded comparison group received only basic self-management education. T tests and effect sizes were used to quantify the difference between the study intervention and comparison groups. Statistical significance was determined for the following outcome variables: A1C ( P < .01), body mass index ( P < .04), and PAM® ( P < .001). Includes strengths, limitations, and future study recommendations. Positive effects of marketplace clinics and community health complementation were found with regard to improved blood glucose control, weight loss, and healthful lifestyle adaptation. Primary care and community health improvements could be realized by incorporating patient activation with diabetes prevention programs for the urban Indian two-thirds majority of the United States 5 million American Indian population.


Multiparameter flow cytometric analysis of human fetal bone marrow B cells.
Maturation of adult human bone marrow (BM) B cells is accompanied by the sequential acquisition and loss of characteristic cell surface antigens (Loken et al., Blood 70:1316). Little is known about these changes in fetal BM B cells. In order to compare fetal with adult B cell development, we performed three-color, flow cytometric analyses of cell surface antigens, as well as nuclear TdT staining, on lymphoid cells from fetal BM. Mononuclear cells isolated from fetal BM (18-22 weeks) were stained with combinations of antibodies against CD3, CD10, CD19, CD20, CD21, CD22, CD34, CD45, PCA-1, IgM, and HLA-DR. Analysis of six separate fetal BM specimens indicated that combinations of cell surface antigens were expressed on analogous populations in fetal and adult BM. Consistent with adult BM, greater than 95% of TdT+ cells within the CD10+ population were CD34+, whereas less than 5% were CD34-. This CD10+/CD34+/TdT+ population constituted 30-40% of the total B cell compartment, compared with 10% in adults. Quantitative changes in CD45 expression on fetal BM B cells defined three clear populations, as has been observed in adults. In striking contrast to adult BM, greater than 95% of CD19+ and greater than 95% of surface IgM+ cells were CD10+, indicating that CD10 is a pan-B cell antigen in fetal BM. Virtually no mature B cells expressing CD21, CD22, or PCA-1 were detected in fetal BM. Our results indicate a preponderance of immature phenotypes exist in the fetal BM B cell compartment. These immature cells can be grouped into three distinct populations, and probably correspond to expanded populations found less frequently in adult BM. This striking increase in the earliest identifiable stages of B cell ontogeny is consistent with an active expansion of cells destined to constitute the humoral immune system during fetal development.


5-Aminolevulinic Acid-Induced Fluorescence in Cerebellar Primary Central Nervous System Lymphoma: A Case Report and Literature Review.
5-Aminolevulinic acid (5-ALA)-induced fluorescence-guided resection is a widely used procedure for patients with malignant gliomas. However, the clinical application of 5-ALA for surgery in primary central nervous system lymphoma (PCNSL) is uncommon. Here, we present a case of PCNSL treated using 5-ALA-induced fluorescence-guided resective surgery. A 70-year-old woman presented with cerebellar ataxia, and magnetic resonance imaging revealed an irregularly shaped and homogenously enhanced mass with surrounding brain edema in the vermis that extended to the right hemisphere of the cerebellum. Under the preoperative diagnosis of a malignant glioma in the cerebellum, the patient underwent 5-ALA-induced fluorescence-guided surgery. Under blue light illumination, the tumor revealed strong 5-ALA-induced fluorescence. The tumor was identified as a diffuse large B-cell lymphoma. After partial resection, the patient received adjuvant chemotherapy and radiotherapy. Importantly, the neurological deficit of the patient improved, and recurrence of the tumor was not observed 21 months post-surgery. Together with previous reports, this case study emphasizes the efficacy of the surgical application of 5-ALA for PCNSL.


Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.
Rheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis. A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer <200 U/ml and cryoglobulins were not detected. The results of her hepatitis serology, retroviral screening, and malignancy screening were negative. Her erythrocyte sedimentation rate was 110 mm in the first hour, and her C-reactive protein level was 45 mg/dl. Her liver profile showed hypoalbuminemia of 28 g/dl. She was treated with immunomodulators and had a good recovery of her renal function. This case illustrates a rare presentation of antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis in a patient with rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.


Changes of rat urinary bladder during acute phase of spinal cord injury.
Spinal cord injury (SCI) at Th13 was induced in female Wistar rats, and changes in the urinary bladder were examined during the acute phase of SCI. Wet weights of the spinal bladders increased twofold over controls by 7 days after SCI. Intravesical volumes increased sixfold over control values by day 3, and then decreased 7 days after the injury. Maximal pressure within the bladder decreased in all spinal rats compared with controls. Smooth muscle cells were isolated from the urinary bladder, and their total protein and DNA content were measured by multiparametric cytofluorometry. DNA content of isolated smooth muscle cells decreased by day 3 and remained 7 days after the spinal injury. Total protein content of isolated smooth muscle cells was decreased 1 day after and increased 7 days after the spinal injury, just when spinal reflex of the bladder recovered. These findings suggest that hypertrophy of smooth muscle cells in urinary bladder is related to the activity of peripheral autonomic nerve and that smooth muscle cells already begin to hypertrophy during the spinal shock period to adjust themselves to the new state, that is, the spinal bladder.


[House call activity by emergency medical services and unusual emission conditions].
Some 65,000 requests for visits by Emergency Aid (SMH) at First-Aid Station Berlin (capital of the GDR) had been noticed in winter 1981/82. About 25,000 requests for visits were only because of cardio-circulatory and respiratory system-symptoms. The number of these requests for visits increased continuously from January to March, especially during days of epidemic situations (acute respiratory diseases--ARD), but also after a period of time with high temperature, humidity and after föhn-weather. Anyfurther increase of requests for visits by Emergency Aid during the extraordinary immission situation (Smog) in January 1982 were not reported.


[Morphologic studies in criminal justice--requirements and reality].
A critical analysis is given of the investigation and examination of fatalities for the public prosecution office and for the courts. Rationalistic simplifications in legal quarters, changes in legal procedures and bureaucracy have had negative effects on the field of forensic medicine. It is questionable whether forensic science today can fulfil the scientific demands with regard to a complete and thorough explanation of the cause of death. The reduced interest in expert opinions concerning the pattern of injuries that can help in the reconstruction of the act or in judging the intention and guilt of the perpetrator is a striking and alarming development in criminal justice. Medical examinations in the somatic field are no longer used enough in forensic cases; with regard to the administration of justice, the role of the forensic expert is limited to the postmortem findings and the cause of death. On the other hand, there is increased interest in the expert opinion of psychologists, psychiatrists and specialists in the field of drugs and alcohol. The fact that the number of autopsies and histological as well as toxicological examinations ordered by the public prosecutor is rather small has serious and negative implications for establishing the truth. Such orders are merely dependent on the circumstance of death and the situation in which the body was found. However, the external circumstances can be misleading or they can be manipulated. That is why some crimes are not revealed. In the Federal Republic of Germany, if there is no suspicion of external violence permission is granted for corpses to be buried without the cause of death being clarified by autopsy. However, the fact that the opinions of forensic specialists differ regarding this development in the administration of justice must also be criticized. There is an increasing tendency for investigations to be carried out only if they are ordered by the prosecutor and for questions to be answered only if they are asked officially. Even our colleagues are influenced too much by external circumstances and consider an autopsy unnecessary if the cause of death seems to be clear (for instance in cases of hanging, drowning or bleeding to death). Second autopsies have shown that the thoroughness and the quality of the first autopsy often leave much to be desired. It is, for instance, unforgivable if organs are described without being examined. Special interest is afforded to the necessity for the significance of histological examinations.(ABSTRACT TRUNCATED AT 400 WORDS)


Regrowth mechanism for oxide isolation of GaAs nanowires.
Oxide-isolated GaAs nanowires (NWs) were obtained through a lithography-free method in which axial growth of NWs coated in aluminum oxide (Al2O3) is restarted using an annealing step. NWs are grown using the vapor-liquid-solid method and coated in nanometer thin oxide films using atomic layer deposition. Continued growth at the oxide-coated nanoparticle (NP) occurs after the thermally-induced fracture of the oxide during annealing. This oxide fracture is observed to depend on NP diameter, oxide thickness and annealing temperature. A thermal expansion mismatch model for stresses on the oxide shell is put forward to explain these results.


Scale-similarity model for Lagrangian velocity correlations in isotropic and stationary turbulence.
A scale-similarity model for Lagrangian two-point, two-time velocity correlations (LVCs) in isotropic turbulence is developed from the Kolmogorov similarity hypothesis. It is a second approximation to the isocontours of LVCs, while the Smith-Hay model is only a first approximation. This model expresses the LVC by its space correlation and a dispersion velocity. We derive the analytical expression for the dispersion velocity from the Navier-Stokes equations using the quasinormality assumption. The dispersion velocity is dependent on enstrophy spectra and shown to be smaller than the sweeping velocity for the Eulerian velocity correlation. Therefore, the Lagrangian decorrelation process is slower than the Eulerian decorrelation process. The data from direct numerical simulation of isotropic turbulence support the scale-similarity model: the LVCs for different space separations collapse into a universal form when plotted against the separation axis defined by the model.


Rhenium-188 mercaptoacetyltriglycine-filled balloon dilation in the treatment of recurrent urethral strictures: initial experience with five patients.
To evaluate the efficacy of beta-irradiation therapy with use of a rhenium-188 mercaptoacetyltriglycine ((188)Re-MAG(3))-filled balloon for the prevention of restenosis in urethral strictures refractory to repetitive surgical or interventional procedures. Five male patients with traumatic (n = 4) or postoperative anastomotic (n = 1) recurrent urethral strictures were included. One to four sessions of 20-30 Gy beta-irradiation at a 1-mm tissue depth with (188)Re-MAG(3)-filled balloon dilation were undertaken in each patient. No procedural complications or toxicities were noted. During the mean follow-up period of 16.2 months, the stricture did not recur in two patients, whereas three patients required additional interventional procedures. In two of these patients, the treatment intervals between the required sessions were significantly prolonged. For the entire group, the mean treatment interval was prolonged from 2.2 months before (188)Re-MAG(3)-filled balloon dilation to 10.7 months after therapy. (188)Re-MAG(3)-filled balloon dilation shows promise in preventing or delaying stricture recurrence in patients with recurrent urethral strictures.


The measurement of uncertainty in illness.
The purpose of this investigation was to explore the role of uncertainty as a significant variable influencing patients' experiences in illness, treatment, and hospitalization. A theory was proposed on uncertainty in illness. Based upon this conceptualization, a 30-item scale tapping the uncertainty in symptomatology, diagnosis, treatment, relationship with care-givers, and planning for the future was developed. The Mishel Uncertainty in Illness Scale (MUIS) was factor analyzed and two factors were extracted from the data. Replication of the factor analysis provided support for the robustness of each factor. The reliability coefficient for each factor of the MUIS was highly adequate for both the initial and replication analyses. Three validation studies were conducted. Initial support for construct validity of the scale was demonstrated by the finding that the MUIS discriminates between treatment groups according to expected differences. Support for theoretical predictions was evidenced by the significant correlation between the MUIS and stress as measured by the Hospital Stress Events Scale. Convergent validity was supported by the finding that the MUIS correlates significantly with lack of comprehension.


Modes and clustering for time-warped gene expression profile data.
The study of the dynamics of regulatory processes has led to increased interest for the analysis of temporal gene expression level data. To address the dynamics of regulation, expression data are collected repeatedly over time. It is difficult to statistically represent the resulting high-dimensional data. When regulatory processes determine gene expression, time-warping is likely to be present, i.e. the sample of gene expression trajectories reflects variation not only in terms of the expression amplitudes, but also in terms of the temporal structure of gene expression. A non-parametric time-synchronized iterative mean updating technique is proposed to find an overall representation that corresponds to a mode of a sample of expression profiles, viewed as a random sample in function space. The proposed algorithm explores the application of previous work of Hall and Heckman to genome-wide expression data and provides an extension that includes random time-warping with the aim to synchronize timescales across genes. The proposed algorithm is universally applicable for the construction of modes for functional data with time-warping. We demonstrate the construction of mode functions for a sample of Drosophila gene expression data. The algorithm can be applied to define clusters among the observed trajectories of gene expression, without any kind of prior non-time-warped clustering, as illustrated in the numerical example.


Cdc1 is required for growth and Mn2+ regulation in Saccharomyces cerevisiae.
Cdc1 function was initially implicated in bud formation and nuclear division because cdc1(Ts) cells arrested with a small bud, duplicated DNA, and undivided nucleus. Our studies show that Cdc1 is necessary for cell growth at several stages of the cell cycle, as well as in pheromone-treated cells. Thus, Cdc1 depletion might affect bud formation and nuclear division, as well as other cellular processes, by blocking a process involved in general cell growth. Cells depleted of intracellular Mn2+ also exhibit a cdc1-like phenotype and recent results suggested Cdc1 might be a Mn2+-dependent protein. We show that all of the conditional Cdc1(Ts) alleles tested cause cells to become sensitive to Mn2+ depletion. In addition, Cdc1 overproduction alleviates the chelator sensitivity of several Mn2+ homeostasis mutants. These findings are compatible with a model in which Cdc1 regulates intracellular, and in particular cytosolic, Mn2+ levels which, in turn, are necessary for cell growth.