It has been shown that sunlit snow and ice plays an important role in processing atmospheric species. Photochemical production of a variety of chemicals has recently been reported to occur in ...snow/ice and the release of these photochemically generated species may significantly impact the chemistry of the overlying atmosphere. Nitrogen oxide and oxidant precursor fluxes have been measured in a number of snow covered environments, where in some cases the emissions significantly impact the overlying boundary layer. For example, photochemical ozone production (such as that occurring in polluted mid-latitudes) of 3–4 ppbv/day has been observed at South Pole, due to high OH and NO levels present in a relatively shallow boundary layer. Field and laboratory experiments have determined that the origin of the observed NOx flux is the photochemistry of nitrate within the snowpack, however some details of the mechanism have not yet been elucidated. A variety of low molecular weight organic compounds have been shown to be emitted from sunlit snowpacks, the source of which has been proposed to be either direct or indirect photo-oxidation of natural organic materials present in the snow. Although myriad studies have observed active processing of species within irradiated snowpacks, the fundamental chemistry occurring remains poorly understood. Here we consider the nature of snow at a fundamental, physical level; photochemical processes within snow and the caveats needed for comparison to atmospheric photochemistry; our current understanding of nitrogen, oxidant, halogen and organic photochemistry within snow; the current limitations faced by the field and implications for the future.
Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are ...required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in ...June 2002.
A systematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer.
Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery.
Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.
The mesosphere/lower thermosphere (MLT, 80–100 km) region is an important boundary between Earth's atmosphere below and space above and may act as a sensitive indicator for anthropogenic climate ...change. Existing observational and modeling studies have shown the middle atmosphere and the MLT is cooling and contracting because of increasing greenhouse gas emissions. However, trend analyses are highly sensitive to the time periods covered, their length, and the measurement type and methodology used. We present for the first time the linear and 11‐year solar cycle responses in the meteor ablation altitude distributions observed by 12 meteor radars at different locations. Decreasing altitudes were seen at all latitudes (linear trends varying from −10.97 to −817.95 m dec−1), and a positive correlation with solar activity was seen for most locations. The divergence of responses at high latitudes indicates an important and complex interplay between atmospheric changes and dynamics at varying time scales.
Plain Language Summary
High up in our atmosphere lies the mesosphere/lower thermosphere region (80–100 km); an important transition zone between the atmosphere below and space above. Existing studies indicate that this region is changing (cooling and contracting) in response to increasing greenhouse gas emissions, quite unlike the net warming we see near the surface. However these trend studies are often highly sensitive to choice and length of time period covered, and the methodology and type of measurements used. Here we present for the first time a self‐consistent methodology applied to 12 different meteor radar station datasets located at a diverse range of latitudes. We looked at changes in the mean peak altitude of individual meteoroid detections, and found decreasing peak altitudes at all locations examined (linear trends varying from −10.97 to −817.95 m decade−1) consistent with a global cooling and contracting of the upper atmosphere. We also examined the response to the 11‐year solar cycle and found a positive correlation with solar activity (i.e., increased meteoroid peak altitudes during solar maximum, and vice versa) for low and mid‐latitude locations. However we found an anti‐correlation at high latitudes suggestive of an important and complex interplay between atmospheric changes and dynamics at varying time scales.
Key Points
Use of geographically diverse meteor radar peak detection altitudes to assess long‐term and 11‐year solar cycle (SC) trends in mesopause region
The altitude of observed peak meteor height has decreased over time at all locations, regardless of latitude and data set
Positive correlation at low‐ and mid‐latitude locations with the 11‐year SC, but more complex response at high‐latitudes
Pertussis is a severe respiratory tract infection caused by Bordetella pertussis. This bacterium infects the ciliated epithelium of the human airways. We investigated the epithelial cell response to ...B. pertussis infection in primary human airway epithelium (HAE) differentiated at air-liquid interface. Infection of the HAE cells mimicked several hallmarks of B. pertussis infection such as reduced epithelial barrier integrity and abrogation of mucociliary transport. Our data suggests mild immunological activation of HAE by B. pertussis indicated by secretion of IL-6 and CXCL8 and the enrichment of genes involved in bacterial recognition and innate immune processes. We identified IL-1β and IFNγ, present in conditioned media derived from B. pertussis-infected macrophage and NK cells, as essential immunological factors for inducing robust chemokine secretion by HAE in response to B. pertussis. In transwell migration assays, the chemokine-containing supernatants derived from this HAE induced monocyte migration. Our data suggests that the airway epithelium on its own has a limited immunological response to B. pertussis and that for a broad immune response communication with local innate immune cells is necessary. This highlights the importance of intercellular communication in the defense against B. pertussis infection and may assist in the rational design of improved pertussis vaccines.
Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only ...glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include ‘off-label’ use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors’ own experience with available drugs derived under very similar health care conditions.
Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis).
This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The pneumoperitoneum is the crucial element in laparoscopic surgery. Different clinical problems are associated with this procedure, which has led to various modifications of the technique. The aim ...of this guideline is to define the scientifically proven standards of the pneumoperitoneum.
Based on systematic literature searches (Medline, Embase, and Cochrane), an expert panel consensually formulated clinical recommendations, which were graded according to the strength of available literature evidence.
Preoperatively, all patients should be assessed for the presence of cardiac, pulmonary, hepatic, renal, or vascular comorbidity. Presupposing appropriate perioperative measures and surgical technique, there is no reason to contraindicate pneumoperitoneum in patients with peritonitis or intraabdominal malignancy. During laparoscopy, monitoring of end tidal CO2 concentration is mandatory. The available data on closed- (Veress needle) and open-access techniques do not allow us to principally favor the use of either technique. Using 2 to 5-mm instead of 5 to 10-mm trocars improves cosmetic result and postoperative pain marginally. It is recommended to use the lowest intraabdominal pressure allowing adequate exposure of the operative field, rather than using a routine pressure. In patients with limited cardiac, pulmonary, or renal function, abdominal wall lifting combined with low-pressure pneumoperitoneum might be an alternative. Abdominal wall lifting devices have no clinically relevant advantages compared to low-pressure (5-7 mmHg) pneumoperitoneum. In patients with cardiopulmonary diseases, intra- and postoperative arterial blood gas monitoring is recommended. The clinical benefits of warmed, humidified insufflation gas are minor and contradictory. Intraoperative sequential intermittent pneumatic compression of the lower extremities is recommended for all prolonged laparoscopic procedures. For the prevention of postoperative pain a wide range of treatment options exists. Although all these options seem to reduce pain, the data currently do not justify a general recommendation.
The teleconnection between the quasi-biennial oscillation (QBO) and the Arctic stratospheric polar vortex, or the Holton–Tan (HT) relationship, may change in a warmer climate or one with ...stratospheric aerosol intervention (SAI) compared to the present-day climate (PDC). Our results from an Earth system model indicate that, under both global warming (based on RCP8.5 emission scenario) and SAI scenarios, the HT relationship weakens in early winter (November–December), although it is closer to PDC under SAI than under the RCP8.5 scenario. In contrast, the HT relationship in the middle to late winter period (January–February) does not change considerably
in response to either RCP8.5 or SAI scenarios compared to PDC. While the weakening of the HT relationship under the RCP8.5 scenario is likely due to the weaker QBO wind amplitudes at the Equator, another physical mechanism must be responsible for the weaker HT relationship under SAI scenarios, since the amplitude of the QBO wind is comparable to the PDC. The strength of the polar vortex does not change under the RCP8.5 scenario compared to PDC, but it becomes stronger under SAI; we attribute the weakening of the HT relationship under SAI to a stronger polar vortex. In general, the changes in the HT relationship cannot be explained by changes to the critical line; the changes in the residual circulation (particularly due to the gravity wave contributions) are important in explaining the changes in the HT relationship under RCP8.5 and SAI scenarios.
Cronartium ribicola, the introduced pathogen that causes white pine blister rust (WPBR), continues to spread to additional limber pine populations in the Southern Rocky Mountains of Colorado and ...Wyoming. Because WPBR can severely impact ecosystems, forecasts of its potential distribution and incidence would be useful to land managers. Site and climate data from long infested study areas in Wyoming were fit with two regression models logistic and classification and regression trees (CART) to determine the environmental conditions associated with the distribution of WPBR. These models were then used to map limber pine stands at risk of infestation by C. ribicola throughout Wyoming (where it has long occurred) and Colorado (where it is just becoming established). Although variables representing vegetation and landform could identify infested plots, 1‐km‐scale climate variables for monthly temperature and moisture were better predictors of current WPBR distribution and were available for mapping expected future distribution across the region. Of 280 485 ha where limber pine was projected to occur in Colorado, 41% was forecast by the logistic model to be at risk of infestation, and 53%, by the CART model. Of an estimated 782 229 ha in Wyoming with limber pine, the logistic model projected 61% to be at risk; CART projected 79%. Additional regression models were fit with site and climate data to predict WPBR incidence (per cent of trees infected) and intensification (incidence/age of the oldest canker). Nearly one half of the plot‐to‐plot variation in incidence was explained using environmental variables readily available to land managers. Although mean plot incidence increased over time, mean intensification decreased 50% per decade. This work provides managers with several tools to reduce uncertainty over the expected distribution and incidence of WPBR, but surveillance and monitoring remain prudent activities for supplementing forecasts of WPBR epidemics.
Highlights ► We investigate DCs of healthy older (≥65 years) and young adults (20–40 years). ► DCs of older adults show an impaired activation of influenza-specific CD8+ T cells. ► Mature DCs of ...older adults express less TNF-α, HLA class I and maturation markers. ► Supplementing TNF-α restores DC function of older adults. ► TNF-α is a major factor in the DC-mediated CD8+ T cell response against influenza.