Levels of Free Granulocyte Elastase in Bronchial Secretions from Patients with Cystic Fibrosis: Effect of Antimicrobial Treatment Against Pseudomonas aeruginosa

Large amounts of free granulocyte elastase (GE), an enzyme capable of mediating airway damage, have been found in bronchial secretions of patients with cystic fibrosis who are infected with Pseudomonas aeruginosa. This finding indicates an imbalance between GE and its antiproteases, α1-proteinase inhibitor (α1-PI) and bronchial mucosal inhibitor (BMI), in the airways of these individuals. The effect of intravenous antimicrobial treatment against P. aeruginosa on activity and concentration of GE, BMI, and α1-PI was evaluated in 30 treatment courses of 20 patients with cystic fibrosis. Although sputum volume and level of immunoreactive GE decreased and concentrations of α1-PI and BMI increased significantly (P < .05), a high level of free GE persisted. No active α1-PI and BMI were detectable after treatment. High levels of GE correlated with a poor pulmonary condition (rs = .98, P < .001). In vitro, elastolytic activity of bronchial secretions from patients with cystic fibrosis was significantly inhibited by eglin C and an oxidation-resistant variant of α1-PI, both compounds currently produced by recombinant DNA technolog

Deepening trochleoplasty with a thick osteochondral flap for patellar instability:Clinical and functional outcomes at mean 6 year follow-up

Background: In patients with patellar instability and severe trochlear dysplasia, trochleoplasty has become increasingly used as part of the surgical management. Hypothesis: Deepening trochleoplasty for severe dysplasia in patellofemoral instability improves function and increases sports participation. Study Design: Case series; Level of evidence, 4. Methods: Between 1995and 2010 the thick-flap deepening trochleoplasty was performed in 90 patients (107 knees) with severe trochlear dysplasia. Data was collected prospectively pre-operatively, at 6 weeks and 1-year follow-up. The patients were surveyed retrospectively to determine the clinical and functional outcomes including sports and exercise participation at a minimum of 2 years, with complete data available in 92%. Results: With a minimum follow-up of 2 years, average of 6 years (range 2 – 19 years). The Kujala score had a median and interquartile range (IQR) of 63 (47-75) pre-operatively rising to 79 (68-91) at 1 year follow-up and 84 (73-92) at final follow-up (p< 0.05). Seventy-two per cent were satisfied with their knee function at 1 year follow-up rising to 79% at final follow-up (p <0.0001). Sports and exercise participation increased from 36 patients (40%) pre-operatively to 60 (67%) at final follow-up. The numbers involved in competitions increased slightly from 10 (11%) to 11 (12%). Of those sports that involved twisting (e.g. soccer, cricket, badminton), the proportion of patients participation increased from 16 (18%) to 22 (24%), whereas in non-twisting sports (e.g. running, swimming, cycling) it increased from 24 (27%) to 47 (52%) of whom 14 (16%) used walking as exercise. Conclusion: The thick-flap deepening trochleoplasty improves the clinical and functional outcomes for patients with symptomatic patellar instability with severe trochlear dysplasia. These results improve over time and beyond the 1 year clinical follow-up. However trochleoplasty does not lead to a significant improvement in sports participation at a competitive level. It does improve the sports and exercise patient participation, principally in non-twisting sports activities

High energy solar neutrinos and p-wave contributions to ^3He(p,\nue^+)^4He

High energy solar neutrinos can come from the hep reaction ^3He(p,\nue^+)^4He with a large end point energy of 18.8 MeV. Understanding the hep reaction may be important for interpreting solar neutrino spectra. We calculate the contribution of the axial charge transition $^3P_0\to ^1S_0$ to the hep thermonuclear S factor using a one-body reaction model involving a nucleon moving in optical potentials. Our result is comparable to or larger than previous calculations of the s-wave Gamow Teller contribution. This indicates that the hep reaction may have p-wave strength leading to an enhancement of the S factor.Comment: 4 pages, 1 ps figure, very minor changes, Phys. Rev. C in pres

Kelp Forest Ecosystems: Biodiversity, Stability, Resilience and Future

Kelp forests are phyletically diverse, structurally complex and highly productive components of cold-water rocky marine coastlines. This paper reviews the conditions in which kelp forests develop globally and where, why and at what rate they become deforested. The ecology and long archaeological history of kelp forests are examined through case studies from southern California, the Aleutian Islands and the western North Atlantic, well-studied locations that represent the widest possible range in kelp forest biodiversity. Global distribution of kelp forests is physiologically constrained by light at high latitudes and by nutrients, warm temperatures and other macrophytes at low latitudes. Within mid-latitude belts (roughly 40-60degrees latitude in both hemispheres) well-developed kelp forests are most threatened by herbivory, usually from sea urchins. Overfishing and extirpation of highly valued vertebrate apex predators often triggered herbivore population increases, leading to widespread kelp deforestation. Such deforestations have the most profound and lasting impacts on species-depauperate systems, such as those in Alaska and the western North Atlantic. Globally urchin-induced deforestation has been increasing over the past 2-3 decades. Continued fishing down of coastal food webs has resulted in shifting harvesting targets from apex predators to their invertebrate prey, including kelp-grazing herbivores. The recent global expansion of sea urchin harvesting has led to the widespread extirpation of this herbivore, and kelp forests have returned in some locations but, for the first time, these forests are devoid of vertebrate apex predators. In the western North Atlantic, large predatory crabs have recently filled this void and they have become the new apex predator in this system. Similar shifts from fish- to crab-dominance may have occurred in coastal zones of the United Kingdom and Japan, where large predatory finfish were extirpated long ago. Three North American case studies of kelp forests were examined to determine their long history with humans and project the status of future kelp forests to the year 2025. Fishing impacts on kelp forest systems have been both profound and much longer in duration than previously thought. Archaeological data suggest that coastal peoples exploited kelp forest organisms for thousands of years, occasionally resulting in localized losses of apex predators, outbreaks of sea urchin populations and probably small-scale deforestation. Over the past two centuries, commercial exploitation for export led to the extirpation of sea urchin predators, such as the sea otter in the North Pacific and predatory fishes like the cod in the North Atlantic. The largescale removal of predators for export markets increased sea urchin abundances and promoted the decline of kelp forests over vast areas. Despite southern California having one of the longest known associations with coastal kelp forests, widespread deforestation is rare. It is possible that functional redundancies among predators and herbivores make this most diverse system most stable. Such biodiverse kelp forests may also resist invasion from non-native species. In the species-depauperate western North Atlantic, introduced algal competitors carpet the benthos and threaten future kelp dominance. There, other non-native herbivores and predators have become established and dominant components of this system. Climate changes have had measurable impacts on kelp forest ecosystems and efforts to control the emission of greenhouse gasses should be a global priority. However, overfishing appears to be the greatest manageable threat to kelp forest ecosystems over the 2025 time horizon. Management should focus on minimizing fishing impacts and restoring populations of functionally important species in these systems

Temperature dependence in interatomic potentials and an improved potential for Ti

The process of deriving an interatomic potentials represents an attempt to integrate out the electronic degrees of freedom from the full quantum description of a condensed matter system. In practice it is the derivatives of the interatomic potentials which are used in molecular dynamics, as a model for the forces on a system. These forces should be the derivative of the free energy of the electronic system, which includes contributions from the entropy of the electronic states. This free energy is weakly temperature dependent, and although this can be safely neglected in many cases there are some systems where the electronic entropy plays a significant role. Here a method is proposed to incorporate electronic entropy in the Sommerfeld approximation into empirical potentials. The method is applied as a correction to an existing potential for titanium. Thermal properties of the new model are calculated, and a simple method for fixing the melting point and solid-solid phase transition temperature for existing models fitted to zero temperature data is presented.Comment: CCP 201

Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury

IMPORTANCE: Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury. OBJECTIVE: To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury. DESIGN, SETTINGS, AND PARTICIPANTS: A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging. MAIN OUTCOMES AND MEASURES: Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid. RESULTS: A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05). CONCLUSIONS AND RELEVANCE: Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy