Cypress terpenes in sawfly larva of Susana cupressi (Hymenoptera: Symphyta: Tenthredinoidea).

Several sawfly species (Hymenoptera: Symphyta) possess larval stages with oesophageal diverticula in which plant compounds are sequestered and used for defence against predators. These organs are present in the larvae of Susana (Tenthredinidae) but remain poorly studied. Here, the aim was to analyse the diverticula extract of Susana cupressi by gas chromatography-mass spectrometry to better understand the ecology of this species. The foliage of the hostplant (Cupressus sempervirens), as well as the larval foregut, midgut, and haemolymph were also analysed. Complementary data were gathered by morphological observations, bioassays using ants, and genetic analyses to identify the studied Susana species. Altogether, 48 terpenes were identified, 30 being sesquiterpenes. The terpenes were generally detected in the foliage, but also in the diverticula, foregut, and midgut, whereas none of them in the haemolymph. The main compounds were alpha-cedrene, alpha-fenchene, alpha-pinene, alpha-terpinyl acetate, beta-myrcene, beta-pinene, cedrol, delta 3-carene, epi-bicyclosesquiphellandrene, germacrene D, limonene, sabinene, and terpinolene. The chemical profiles of these 13 compounds were significantly correlated between foliage-diverticula, diverticula-foregut and foregut-midgut, but not correlated for the three remaining possible comparisons. Alpha-pinene decreased and germacrene D increased from the foliage to the diverticula, which may reflect a specific sequestration of the latter terpene and its known deleterious effects on insects. We conclude that larvae of S. cupressi, similarly to those of diprionids, are well defended against predatory attacks by sequestering and regurgitating hostplant terpenes, including germacrene D.

NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele.

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1ß and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1ß expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

Prevalence of motor impairment in residents of New South Wales, Australia aged 55 years and over: cross-sectional survey of the 45 and Up cohort.

BACKGROUND: The population prevalence of many diseases is known. However, little is known of the population prevalence of motor impairments. METHODS: The aim of this study was to determine the point prevalence of specific motor impairments (weakness, fatigue, contracture, impaired balance and impaired coordination) in the population aged 55 years and older resident in New South Wales, Australia in 2018. 55,210 members of the 45 and Up cohort were invited to participate in a follow-up survey that included questions on motor impairment. Responses were received from 20,141 people (36%). Calibrated estimates of prevalence of specific motor impairments, and of having at least one motor impairment, were obtained using survey weights based on the known multivariate distributions of age, gender and geographical location (28 regions) in the population. RESULTS: More than one-third of adults aged over 55 residing in New South Wales have difficulty using their hands, arms or legs. The prevalence of each motor impairment (muscle weakness, fatigue, contracture, impaired balance or impaired coordination) in this population is between 4 and 12%. The prevalence of at least one of these impairments is 21%. The prevalence of at least one impairment in people aged 85 and over is 42%. Women consistently had more difficulty using hands, arms and legs, and more motor impairment, than men. Difficulty using hands, arms and legs and the prevalence of all motor impairments, especially poor balance, greatly increased with age. CONCLUSION: The prevalence of specific motor impairments in older Australian adults is high - comparable to that of the most prevalent diseases. There may be merit in considering motor impairment as a significant public health problem in its own right.

An Overview on the Development of Electrochemical Capacitors and Batteries - part II.

In the second part of the review on electrochemical energy storage, the devolvement of batteries is explored. First, fundamental aspects of battery operation will be given, then, different materials and chemistry of rechargeable batteries will be explored, including each component of the cell. In negative electrodes, metallic, intercalation and transformation materials will be addressed. Examples are Li or Na metal batteries, graphite and other carbonaceous materials (such as graphene) for intercalation of metal-ions and transition metal oxides and silicon for transformation. In the positive electrode section, materials for intercalation and transformation will be reviewed. The state-of-the-art on intercalation as lithium cobalt oxide and nickel containing oxides will be approached for intercalation materials, whereas sulfur and metal-air will also be explored for transformation. Alongside, the role of electrolyte will be discussed concerning performance and safety, with examples for the next generation devices. Finally, a general future perspective will address both electrochemical capacitors and batteries.

An Overview on the Development of Electrochemical Capacitors and Batteries - Part I.

The Nobel Prize in Chemistry 2019 recognized the importance of Li-ion batteries and the revolution they allowed to happen during the past three decades. They are part of a broader class of electrochemical energy storage devices, which are employed where electrical energy is needed on demand and so, the electrochemical energy is converted into electrical energy as required by the application. This opens a variety of possibilities on the utilization of energy storage devices, beyond the well-known mobile applications, assisting on the decarbonization of energy production and distribution. In this series of reviews in two parts, two main types of energy storage devices will be explored: electrochemical capacitors (part I) and rechargeable batteries (part II). More specifically, we will discuss about the materials used in each type of device, their main role in the energy storage process, their advantages and drawbacks and, especially, strategies to improve their performance. In the present part, electrochemical capacitors will be addressed. Their fundamental difference to batteries is explained considering the process at the electrode/electrolyte surface and the impact in performance. Materials used in electrochemical capacitors, including double layer capacitors and pseudocapacitive materials will be reviewed, highlighting the importance of electrolytes. As an important part of these strategies, synthetic routes for the production of nanoparticles will also be approached (part I).

Immunohistochemical Characterization of Sarcomas in Trp53+/- Haploinsufficient Mice.

The use of immunohistochemical (IHC) staining in determining and/or confirming the cellular origin of poorly differentiated sarcomas was evaluated in this study. Sarcomatous neoplasms were evaluated in a research study conducted in 2 strains of p53+/- haploinsufficient mice. The most common neoplasms were undifferentiated sarcomas, followed by osteosarcomas and rhabdomyosarcomas (RMSs). The RMSs were poorly differentiated and appeared similar to the pleomorphic, or adult type, RMS of humans. All sarcomas stained positive by IHC for the mesenchymal cell intermediate filament vimentin. The RMSs were identified by positive IHC staining for myogenin, a transcription factor specific to skeletal muscle. Osteosarcomas were easily identifiable on hematoxylin and eosin-stained slides; no generally accepted IHC stain specific for bone is presently available. Some of the undifferentiated sarcomas contained numerous macrophages that stained positive for F4/80, a macrophage marker; the positive-staining cells were considered to be infiltrating macrophages. One-third of the neoplasms observed in this study were associated with subcutaneous implanted electronic microchips used for animal identification. Based upon histopathologic evaluation and IHC staining, it was not possible to distinguish neoplasms associated with subcutaneous microchips from neoplasms not associated with microchips.

A pilot randomised trial of community-based care following discharge from hospital with a recent spinal cord injury in Bangladesh.

OBJECTIVES: To explore the feasibility of conducting a full trial designed to determine the effectiveness of a model of community-based care for people with spinal cord injury in Bangladesh. STUDY DESIGN: A pilot randomised trial. SETTING: Community, Bangladesh. SUBJECTS: Participants were 30 people with recent spinal cord injury who were wheelchair-dependent and soon to be discharged from hospital. INTERVENTION: Participants randomised to the intervention group received a package of care involving regular telephone contact and three home visits over two years. Participants randomised to the control group received usual care consisting of a telephone call and an optional home visit. MAIN MEASURES: Participants were assessed at baseline and two years after randomization. The primary outcome was mortality and secondary outcomes were measures of complications, depression, participation and quality of life. RESULTS: A total of 24 participants had a complete spinal cord injury and six participants had an incomplete spinal cord injury. Median (interquartile) age and time since injury at baseline were 31 years (24 to 36) and 7 months (4 to 13), respectively. Two participants, one in each group, died. Five participants had pressure ulcers at two years. There were no notable impediments to the conduct of the trial and no significant protocol violations. The phone calls and home visits were delivered according to the protocol 87% and 100% of the time, respectively. Follow-up data were 99% complete. CONCLUSION: This pilot trial demonstrates the feasibility of a full clinical trial of 410 participants, which has recently commenced. SPONSORSHIP: University of Sydney, Australia.

Computational Identification of Antibody Epitopes on the Dengue Virus NS1 Protein.

We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1-4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5.3 were identified, revealing the reasons for the serotype specificity of 1H7.4 and 1G5.3, and the non-selectivity of Gus2. As DENV NS1 is critical for virus replication and a key vaccine candidate, epitope prediction will be valuable in designing appropriate vaccine control strategies. The ability to predict potential epitopes by computational methods significantly reduces the amount of experimental work required to screen peptide libraries for epitope mapping.

Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It?

BACKGROUND: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease. METHODS: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed. RESULTS: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%). CONCLUSIONS: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Psychological and socioeconomic status, complications and quality of life in people with spinal cord injuries after discharge from hospital in Bangladesh: a cohort study.

STUDY DESIGN: Mixed retrospective-prospective cohort study. OBJECTIVES: To determine psychological and socioeconomic status, complications and quality of life in people with spinal cord injuries (SCI) after discharge from a hospital in Bangladesh. SETTING: Bangladesh. METHODS: All patients admitted in 2011 with a recent SCI to a hospital in Bangladesh were identified. Patients were interviewed by telephone in 2014 using translated versions of the SF12, the SCI Secondary Conditions Scale, the Centre for Epidemiologic Studies Depression Scale (CESDS) and the Participation Component of the WHODAS. Questions were also asked about employment, living and financial situation, and opportunities to get out of bed and out of the house. Data were stratified by ability to walk on discharge. RESULTS: A total of 350 people were discharged with a recent SCI in 2011. By 2014, 55 had died. Of those still living, 283 were interviewed (96% follow-up rate). At the time of interview, 47% of participants were employed. One-quarter (26%) of those who were wheelchair-dependent had a pressure ulcer. The mean (s.d.) scores for the Mental and Physical Component of the SF12 were 32.0 points (5.5) and 35.8 points (3.9), respectively. The median (interquartile range) scores for the SCI Secondary Conditions Scale, CESDS and WHODAS for those who were wheelchair-dependent were 15% (10 to 19), 11 points (9 to 18) and 26 points (23 to 26), respectively. CONCLUSION: Many people with SCI in Bangladesh are house-bound, unemployed, living in poverty and have pressure ulcers. They experience moderate rates of depression and report limited quality of life.

Two-year survival following discharge from hospital after spinal cord injury in Bangladesh.

STUDY DESIGN: Mixed retrospective-prospective cohort study. OBJECTIVES: To determine 2-year survival following discharge from hospital after spinal cord injury in Bangladesh. SETTING: Bangladesh. METHODS: Medical records were used to identify all patients admitted in 2011 with a recent spinal cord injury to the Centre for Rehabilitation of the Paralysed, a large Bangladeshi hospital that specialises in care of people with spinal cord injury. Patients or their families were subsequently visited or contacted by telephone in 2014. Vital status and, where relevant, date and cause of death were determined by verbal autopsy. RESULTS: 350 of 371 people admitted with a recent spinal cord injury in 2011 were discharged alive from hospital. All but eleven were accounted for two years after discharge (97% follow-up). Two-year survival was 87% (95% CI 83% to 90%). Two-year survival of those who were wheelchair-dependent was 81% (95% CI 76% to 86%). The most common cause of death was sepsis due to pressure ulcers. CONCLUSION: In Bangladesh, approximately one in five people with spinal cord injury who are wheelchair-dependent die within two years of discharge from hospital. Most deaths are due to sepsis from potentially preventable pressure ulcers.

Changes in the length and three-dimensional orientation of muscle fascicles and aponeuroses with passive length changes in human gastrocnemius muscles.

The mechanisms by which skeletal muscles lengthen and shorten are potentially complex. When the relaxed human gastrocnemius muscle is at its shortest in vivo lengths it falls slack (i.e. it does not exert any passive tension). It has been hypothesised that when the muscle is passively lengthened, slack is progressively taken up, first in some muscle fascicles then in others. Two-dimensional imaging methods suggest that, once the slack is taken up, changes in muscle length are mediated primarily by changes in the lengths of the tendinous components of the muscle. The aims of this study were to test the hypothesis that there is progressive engagement of relaxed muscle fascicles, and to quantify changes in the length and three-dimensional orientation of muscle fascicles and tendinous structures during passive changes in muscle length. Ultrasound imaging was used to determine the location, in an ultrasound image plane, of the proximal and distal ends of muscle fascicles at 14 sites in the human gastrocnemius muscle as the ankle was rotated passively through its full range. A three-dimensional motion analysis system recorded the location and orientation of the ultrasound image plane and the leg. These data were used to generate dynamic three-dimensional reconstructions of the architecture of the muscle fascicles and aponeuroses. There was considerable variability in the measured muscle lengths at which the slack was taken up in individual muscle fascicles. However, that variability was not much greater than the error associated with the measurement procedure. An analysis of these data which took into account the possible correlations between errors showed that, contrary to our earlier hypothesis, muscle fascicles are not progressively engaged during passive lengthening of the human gastrocnemius. Instead, the slack is taken up nearly simultaneously in all muscle fascicles. Once the muscle is lengthened sufficiently to take up the slack, about half of the subsequent increase in muscle length is due to elongation of the tendinous structures and half is due to elongation of muscle fascicles, at least over the range of muscle-tendon lengths that was investigated (up to ∼60 or 70% of the range of in vivo lengths). Changes in the alignment of muscle fascicles and flattening of aponeuroses contribute little to the total change in muscle length.

Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials.

BACKGROUND: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). OBJECTIVES: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). METHODS: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. RESULTS: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. CONCLUSIONS: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Progress to Date and Future Plans.

The International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice proposal (INHAND) has been operational since 2005. A Global Editorial Steering Committee manages the overall objectives of the project, and the development of harmonized terminology for each organ system is the responsibility of the Organ Working Groups, drawing upon experts from North America, Europe, and Japan. Great progress has been made with 9 systems published to date--respiratory, hepatobiliary, urinary, central/peripheral nervous systems, male reproductive and mammary, zymbals, clitoral, and preputial glands in Toxicologic Pathology and the integument and soft tissue and female reproductive in the Journal of Toxicologic Pathology as supplements and on a Web site--www.goReni.org. INHAND nomenclature guides offer diagnostic criteria and guidelines for recording lesions observed in rodent toxicity and carcinogenicity studies. The guides provide representative photomicrographs of morphologic changes, information regarding pathogenesis, and key references. The purpose of this brief communication is to provide an update on the progress of INHAND.

Parathyroid surgery in the elderly: should minimally invasive surgery be abandoned?

BACKGROUND: Single adenoma is the cause of 80 % of primary hyperparathyroidism (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy (MIP). The incidence of PHPT increases with age. Little information is available regarding the prevalence of multiglandular disease (MGD) in older patients. METHODS: The records of 537 patients that underwent parathyroid surgery between January 2005 and October 2012 at two endocrine surgery referral centers were retrospectively reviewed. Comparison was performed between patients younger than 65 and older than 65 years of age. Clinical variables included preoperative laboratories and imaging, extent of neck exploration, number of glands excised, and intraoperative parathyroid hormone levels during surgery. RESULTS: There were 374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the older age group (OG). The mean age was 50 ± 0.5 and 71 ± 0.4 years, respectively. There was no difference between the groups in terms of gender or laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %; p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p = 0.27). In the OG, patients with MGD had significantly smaller glands as compared to patients with single adenomas in this group (331 ± 67 vs. 920 ± 97 mg; p = 0.006, respectively). CONCLUSIONS: MGD in PHPT was found to be more prevalent in older patients. Planning a bilateral neck exploration should be considered in older patients, especially when a relatively small gland is suggested by imaging or encountered during surgery.

Trajectories of PTSD risk and resilience in World Trade Center responders: an 8-year prospective cohort study.

BACKGROUND: Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders. METHOD: A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks. RESULTS: Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories. CONCLUSIONS: Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.

Dimensional structure and course of post-traumatic stress symptomatology in World Trade Center responders.

BACKGROUND: Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations. METHOD: Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11. RESULTS: CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time. CONCLUSIONS: Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.

Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy.

OBJECTIVE: To determine the feasibility of administering a diazepam nasal spray formulation (diazepam-NS) to adults with epilepsy during a generalized tonic-clonic seizure or in the postictal period following a tonic-clonic or other seizure type, to assess pharmacokinetics and to assess tolerability. METHODS: An open-label study was conducted in patients admitted to the epilepsy monitoring unit. Eligible patients received a single dose of diazepam-NS approximating 0.2 mg/kg. Plasma diazepam concentrations were measured serially up to 12 h postdose, and maximum observed plasma concentration (Cmax ); time to maximum concentration (Tmax ); and the area under the plasma concentration-time curve for time zero to last sampling time (AUC0-12 ) were estimated and dose-normalized. Pharmacodynamic assessments included Kaplan-Meier analysis to determine the time-to-next seizure. Safety and tolerability were assessed. RESULTS: Of the 78 patients who consented, 30 had treatment and pharmacokinetic data. Ten patients were treated during a convulsive tonic-clonic seizure, seven within 5 min following the last clonic jerk, and 13 in the postictal period ≥ 5 min after a tonic-clonic or following other seizure-types. Diazepam median Tmax was 45 min. Dose-normalized mean Cmax and AUC0-12 values of diazepam were comparable among patients regardless of the timing of diazepam-NS administration in relation to seizure. Of those treated, 65% were seizure-free during the 12-h observation period and 35% had post-dose seizures. Treatment was well tolerated, with no unexpected safety findings: 74% had mild and 25% had moderate adverse events. Nasopharyngeal signs were resolved by 12 h postdose. SIGNIFICANCE: Diazepam can be delivered in effective therapeutic concentrations by a nasal spray device during the convulsive phase of tonic-clonic seizures or in the postictal periods following tonic-clonic or other seizure types.

Predator-prey systems depend on a prey refuge.

Models of near-exclusive predator-prey systems such as that of the Canadian lynx and snowshoe hare have included factors such as a second prey species, a Holling Type II predator response and climatic or seasonal effects to reproduce sub-sets of six signature patterns in the empirical data. We present an agent-based model which does not require the factors or constraints of previous models to reproduce all six patterns in persistent populations. Our parsimonious model represents a generalised predator and prey species with a small prey refuge. The lack of the constraints of previous models, considered to be important for those models, casts doubt on the current hypothesised mechanisms of exclusive predator-prey systems. The implication for management of the lynx, a protected species, is that maintenance of an heterogeneous environment offering natural refuge areas for the hare is the most important factor for the conservation of this species.

Prospective validation of a surgical complications grading system in a cohort of 2114 patients.

BACKGROUND: We recently reported a grading system for surgical complications. This system proved to have a high sensitivity for recording minor but meaningful complications prolonging hospital stay in patients after colorectal surgery. We aimed to prospectively validate the complication grading system in a general surgery department over 1 year. METHODS: All surgical procedures and related complications were prospectively recorded between January 1st and December 31st, 2009. Surgical complications were graded on a severity scale of 1-5. The system classifies short-term outcome by grade emphasizing intensity of therapy required for treatment of the defined complication. RESULTS: During the study period, 2114 patients underwent surgery. Elective and oncological surgeries were performed in 1606 (76%) and 465 (22%) patients, respectively. There were 422 surgical complications in 304 (14%) patients (Grade 1/2: 203 [67%]; Grade 3/4: 90 [29%]; Grade 5: 11 [4%]). Median length of stay correlated significantly with complication severity: 2.3 d for no complication, 6.2 and 11.8 d for Grades 1/2 and 3/4, respectively (P < 0.001). Older age (OR 2.75, P < 0.001), comorbidities (OR 1.44, P = 0.02), American Society of Anesthesiology score >2 (OR 2.07, P < 0.001), contamination Grade (OR 1.85, P = 0.001), oncological (OR 2.82, P < 0.001), open (OR 1.22, P = 0.03), prolonged >120 min (OR 2.08, P < 0.001), and emergency surgery (OR 1.42, P = 0.02) independently predicted postoperative complications. CONCLUSIONS: This system of grading surgical complications permits standardized reporting of surgical morbidity according to the severity of impact. Prospective validation of this system supports its use in a general surgery setting as a tool for surgical outcome assessment and quality assurance.