A recent deep earthquake doublet in light of long-term evolution of Nazca subduction.

Earthquake faulting at ~600 km depth remains puzzling. Here we present a new kinematic interpretation of two Mw7.6 earthquakes of November 24, 2015. In contrast to teleseismic analysis of this doublet, we use regional seismic data providing robust two-point source models, further validated by regional back-projection and rupture-stop analysis. The doublet represents segmented rupture of a ∼30-year gap in a narrow, deep fault zone, fully consistent with the stress field derived from neighbouring 1976-2015 earthquakes. Seismic observations are interpreted using a geodynamic model of regional subduction, incorporating realistic rheology and major phase transitions, yielding a model slab that is nearly vertical in the deep-earthquake zone but stagnant below 660 km, consistent with tomographic imaging. Geodynamically modelled stresses match the seismically inferred stress field, where the steeply down-dip orientation of compressive stress axes at ∼600 km arises from combined viscous and buoyant forces resisting slab penetration into the lower mantle and deformation associated with slab buckling and stagnation. Observed fault-rupture geometry, demonstrated likelihood of seismic triggering, and high model temperatures in young subducted lithosphere, together favour nanometric crystallisation (and associated grain-boundary sliding) attending high-pressure dehydration as a likely seismogenic mechanism, unless a segment of much older lithosphere is present at depth.

Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers.

A randomized, controlled, double-blinded study was conducted to determine safety and immunogenicity of five live attenuated dengue vaccines produced by Aventis Pasteur (AvP). The study was completed with 40 flavivirus non-immune volunteers: five recipients of each monovalent (dengue-1, dengue-2, dengue-3, or dengue-4) vaccine, ten recipients of tetravalent (dengue-1, dengue-2, dengue-3, and dengue-4) vaccine, and ten recipients of vaccine vehicle alone. All vaccines were administered in a single subcutaneous dose (range, 3.6-4.4 log(10) plaque forming units). No serious adverse reactions occurred in volunteers followed for 6 months after vaccination. Five vaccine recipients developed fever (T > or = 38.0 degrees C), including four tetravalent vaccinees between days 8 and 10 after vaccination. Dengue-1, dengue-2, dengue-3, or dengue-4 vaccine recipients reported similar frequency of mild symptoms of headache, malaise, and eye pain. Tetravalent vaccinees noted more moderate symptoms with onset from study days 8-11 and developed maculopapular rashes distributed over trunk and extremities. Transient neutropenia (white blood cells < 4000/mm3) was noted after vaccination but not thrombocytopenia (platelets < 100,000/mm3). All dengue-3, dengue-4, and tetravalent vaccine recipients were viremic between days 7 and 12 but viremia was rarely detected in dengue-1 or dengue-2 vaccinees. All dengue-2, dengue-3, and dengue-4, and 60% of dengue-1 vaccine recipients developed neutralizing and/or immunoglobulin M antibodies. All tetravalent vaccine recipients were viremic with dengue-3 virus and developed neutralizing antibodies to dengue-3 virus. Seven volunteers also had multivalent antibody responses, yet the highest antibody titers were against dengue-3 virus. The AvP live attenuated dengue virus vaccines are safe and tolerable in humans. The live attenuated tetravalent dengue vaccine was most reactogenic, and preferential replication of dengue-3 virus may have affected its infectivity and immunogenicity.

A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.

The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.

The dialysis of Ochratoxin A (OTA).

Standard dialysis did not result in a decrease of the OTA level in the blood serum of patients regularly treated by dialysis. Therefore, we examined the effect of dialysis on both OTA bound to the blood plasma proteins and free OTA. We carried out an in vivo experiment to determine OTA levels in the serum of patients in the terminal stage of chronic renal insufficiency (CHRI) before and after dialysis and also in the dialysate in which we did not find OTA. OTA bound to blood plasma proteins did not penetrate the dialysis membrane. In contrast, free OTA during an in vitro experiment with the identical dialyzer (as during the in vivo experiment), easily penetrated the same dialysis membrane.

Growth-inhibiting antibody responses of humans vaccinated with recombinant outer surface protein A or infected with Borrelia burgdorferi or both.

Serial serum samples from a 2-year human trial of outer surface protein (Osp) A vaccine were analyzed by Borrelia burgdorferi growth-inhibition assay (GIA) and anti-OspA ELISA to assess the antibody responses of vaccine recipients and subjects with Lyme disease. Although 74% of OspA recipients had a reciprocal GIA titer >/=64 after 3 vaccinations, none of the placebo recipients, even those with Lyme disease, had a GIA titer this high. The correlation between GIA and ELISA titers after 3 doses of vaccine was.84; however, more vaccine recipients had an elevated ELISA titer paired with low GIA titer than had a low ELISA titer with a high GIA titer. OspA-vaccine recipients who acquired Lyme disease had significantly lower serum GIA and ELISA titers after 3 immunizations than did age- and sex-matched OspA recipients without Lyme disease. Thus, vaccinated subjects had antibodies to native antigen on viable cells, and antibody assays with this specificity may predict protection of vaccinees against infection.

A canarypox vector expressing cytomegalovirus (CMV) glycoprotein B primes for antibody responses to a live attenuated CMV vaccine (Towne).

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Kinetics of phenols in body fluid compartments during hemodialysis.

On the basis of direct quantification of hemodialysis (HD), the kinetics of phenols (Ph) were followed in 13 patients on regular HD treatment. The average plasma levels of Ph before and after HD were 627 +/- 109 mumol/L and 416 +/- 81 mumol/L, respectively. The total amount of Ph removed during 5-h HD was 7,481 +/- 1,894 mumol. For calculation of the generation rate (G), a new formula has been derived not requiring knowledge of the corresponding volume of distribution. The G of Ph was 2.9 +/- 0.7 mumol/min on average. The mean dialysis clearance (K) of Ph was 48.2 +/- 10.2 ml/min.

[Changes in amino acids in a regular dialysis program]. / Aktuální zmeny aminokyselin v pravidelném dialyzacním programu.

BACKGROUND: Dialyzed patients are chronically in a state of negative nitrogen balance, and amino acids, their building stones, are also significantly affected by dialysis. The purpose of the present investigation was to assess whether they should be supplied, how frequently and for how long and how they are influenced by the usual diet of patients. METHODS AND RESULTS: The examination was made in a group of 13 patients included in a regular haemodialysis programme. Their mean age was 53.2 +/- 12.4 years, they were dialyzed for an average period of 55 months, maximum 163 months. The patients were dialyzed three times per week for four hours, bicarbonate dialysate was used. The patients' diet was not modified in any way. A total of 52 haemodialysis were examined: losses of alpha-amino nitrogen were monitored as well as changes of serum concentrations of different amino acids. Their mean losses were 119 +/- 54.69 mmol/4 h: this corresponds to 10.5 +/- 4.8 mg amino acids. The dialysis clearance was on average 122.7 +/- 63.2 ml/min. This value did not differ significantly from the dialysis clearance of urea, but it was significantly higher than creatinine clearance (p < 0.05). During dialysis a significant drop (p < 0.001) of the plasma concentration of amino nitrogen occurred, however, the changes of serum concentrations of amino acids differed. A significant drop was recorded in serum concentrations of histamine, lysine, cysteine, methionine, tyrosine, glycine, asparagine, citrullin, glutamine, taurine. Before the beginning of dialysis the values of valine, lysine, threonine, serine, alanine and asparagine were lower than corresponds to the reference interval in healthy subjects. CONCLUSIONS: Changes of serum concentrations of individual amino acids are significantly influenced not only by their losses into the dialysate but also by their shift from cells into the extracellular fluid and by resorption from the digestive tract during protein intake in the course of dialysis. An adequate supply of high quality protein can compensate for these losses. Investigation of serum concentration of individual amino acids does not record their kinetic changes but can give an idea on the effectiveness of the dietary regime.

Clinical and serological responses following primary and booster immunization with Salmonella typhi Vi capsular polysaccharide vaccines.

Clinical and serum antibody responses following intramuscular injection of two formulations of Salmonella typhi Vi capsular polysaccharide (Vi) were assessed in a double-blind evaluation. Healthy adults were randomly assigned to receive a 25 micrograms dose of liquid (Vi-Liq; n = 182) or freeze-dried Vi vaccine (Vi-Lyoph; n = 55), or placebo (n = 86). Erythema and/or induration > or = 1 cm in diameter at the injection site developed in 13/182 (7%) of Vi-Liq and 3/55 (5%) of Vi-Lyoph recipients (not significant, n.s.). Fever (oral temperature > or = 100 degrees F (37.8 degrees C)) occurred in < 2% of vaccinees. The frequencies of rises of fourfold or greater and of maximal Vi antibody levels were similar in the two vaccine groups. Fourfold or greater rises in serum Vi antibody levels (RIA) developed in 53% of Vi-Lyoph and 60% of Vi-Liq recipients by 1 week (n.s.), and 98 and 93%, respectively, by 1 month (n.s.). The frequencies of adverse reactions and mean Vi antibody levels following booster immunization with Vi-Liq 27 to 34 months after primary immunization (n = 55) were similar to those observed following primary immunization, although subjects given a booster dose were more likely to develop local reactions > or = 1 cm in diameter than those given a first dose (10/55 versus 13/182, p = 0.013 by the chi 2 test). Primary and booster immunizations with the Vi vaccines are well tolerated in healthy adults; mean Vi antibody levels remain significantly elevated for up to 34 months after primary immunization.

[Determination of urea distribution space on the basis of hemodialysis quantification]. / Stanovení distribucního prostoru mocoviny na podklade kvantifikace hemodialýzy.

By using direct dialysis quantification--DDQ--in 124 haemodialyses made in 14 patients the authors assessed the urea output in mmol in the dialyzation fluid collected after every dialysis. The evaluation of total body fluids, which accounts roughly for 60% of the total body weight, was replaced by a calculated distribution space of urea (Vu) according to the Du/Ppre--Ppost formula. This equation was modified with regard to the degree of ultrafiltration and urea formation. The authors found a 5% difference between the values of the modified Vu equation and total body fluids corresponding to 60% of the body weight.

[Determination of lactoferrin in the diagnosis of pancreatopathy in patients with chronic kidney failure]. / Stanovení laktoferinu v diagnostice pankreatopatií u nemocných s chronickým selháním ledvin.

The authors investigated in patients with renal disease the lactoferrin content in duodenal aspirate. The aspirate was obtained after previous stimulation of the pancreas with pancreozymin. Lactoferrin estimation is described in the literature as a sensitive examination of changes of exocrine pancreatic secretion. The authors provided evidence that by assessing lactoferrin it is possible to detect initial changes of reduced exocrine pancreatic capacity already in subjects who are on the waiting list of chronic intermittent haemodialyzation programmes (CHIDP); maximum increase of the lactoferrin content in the duodenal aspirate corresponds with the severity of chronic renal failure. Transplantation of the kidneys leads to normalization of the amount of lactoferrin secreted by the pancreas which is evidence of normalization of pancreatic secretion. In patients with chronic renal failure lactoferrin is a sensitive marker of developing uraemic pancreatopathy.

[Hemorrhage into the digestive tract as a cause of death in patients after kidney transplantation]. / Krvácení do zazívacího traktu jako prícina úmrtí u nemocných po transplantaci ledvin.

The authors investigated the prevalence, cause and possible prevention of haemorrhage into the gastrointestinal tract in 218 patients after transplantation of the kidney (TK). 1. Haemorrhage into the gastrointestinal tract after TK occurred in 32 patients incl. 53.1% who died. In the total mortality after TK haemorrhage into the gastrointestinal tract account for 15.7%. 2. The danger of haemorrhage into the gastrointestinal tract is increased in particular: in the early postoperative period (within one month after transplantation of the kidney), during acute rejection with declining function of the graft, in infectious complications, after graftectomy, in preexisting peptic ulcers. 3. The most frequent cause of haemorrhage were duodenal ulcers. The authors elaborated a system of preventive provisions which involve: a) medicamentous prophylaxis by administration of H2 blockers and antacids not only at the time of transplantation of the kidney and during the early postoperative period but also when there is an increased risk, b) detailed gastroenterological examination before transplantation of the kidney, c) in case of relapsing peptic ulceration in the case-history or haemorrhage into the gastrointestinal tract, subject patients on the waiting list for transplantation of the kidneys during the dialyzation period to proximal gastric vagotomy, or so-called highly selective vagotomy.

Upper gastrointestinal bleeding as a complication in end stage renal disease patients.

The commonest pathological findings in the upper gastrointestinal tract have been verified by studying 320 autopsies as related to chronic renal failure through the 20-year span. In our series of 99 patients having been hospitalized within the period of 1989 to 1990, lesions of upper gastrointestinal tract were summarized that might be responsible for bleeding in the course of the dialysis and after renal transplantation. In accordance with literature sources, the investigated group showed gastric and duodenal mucosal lesions to be the most frequent sources of hemorrhages. For both the early diagnosis and therapy all patients have to be examined prior to the initiation of a regular maintenance dialysis. Gastroscopy is also indicated in all patients without any exception. Subsequent conservative treatment should be performed in an intensive and accurate way. While unsuccessful, the surgery is indicated. Authors referred to indicatory criteria based on surgical management of gastroduodenal ulcer. Both the early diagnosis and indication to surgery were stated to be of crucial importance for patient's destiny when the conservative treatment has failed. The present study should contribute to a closer collaboration of nephrologists, gastroenterologists and surgeons in order to prevent such serious complications that are represented by gastrointestinal bleeding in patients with chronic renal failure.

Simulator for evaluating shoulder motion as a command source for FES grasp restoration systems.

A simulator has been developed to evaluate the command channels through which a quadriplegic patient controls an upper limb neural prosthesis. The simulator consists of an animated grasping task implemented on a video screen. The patient controls the motion of an animated hand on the screen by moving his or her own hand while the animated hand opens and closes under control of the tested command channel. Experiments were performed using both able-bodied and quadriplegic subjects to evaluate shoulder motion as a command-channel source. The results demonstrated that optimal combinations of shoulder command-channel parameters are subject specific, which suggests using the simulator in the prescription of upper limb neural prostheses and in training quadriplegic persons who use them. Additionally, the experimental results quantified the reduction in performance that came from using ipsilateral vs contralateral shoulder control and the enhancement in performance realized when using substitute sensory force-feedback displays.

[Complications of subclavian and femoral cannulas]. / Komplikace podklíckových a femorálních kanyl.

In the course of 15 years in the author's department some 15,000 cannulas were inserted into the subclavian or femoral vein. This number included cca 2300 cannulas inserted to dialyzed patients. 213 patients (inl. 28 dialyzed) died with the inserted cannula. In these patients the incidence of complications was evaluated. A parietal thrombosis was the most frequent complication and was recorded in 119 cases, i.e. in 56% (in non-dialyzed in 57% and in dialyzed in 50%). In two non-dialyzed patients it was the cause of embolization into the lungs. In the incidence of complications there is no significant difference in dialyzed and non-dialyzed patients. For completeness the authors present a preliminary calculation per approximate number of inserted cannulas during this period. From the total number of 15,000 inserted cannulas fatal complications occurred in 0.06% (in dialyzed in 0.13% and non-dialyzed in 0.047%).

[Early acute tubulointerstitial nephropathy in transplanted kidneys]. / Casná akutní tubulointersticiální nefropatie transplantované ledviny.

The authors investigated in a group of 124 patients the effect of acute tubular nephropathy and rejection on the period of functional persistence of transplanted kidneys. Transplants which developed tubulointerstitial nephropathy during the first two weeks after transplantation of the kidney had significantly lower cumulative indexes of survival for as long as the second year after transplantation. Grafts which were rejected during the first two weeks after transplantation had a significantly lower cumulative survival index only during the first and second year. The statistical significance was always tested in comparison with grafts where the postoperative course was uneventful. It is better to evaluate the functional prognosis of transplanted kidneys from the maximal achieved glomerular filtration after a load; it did not matter whether tubulointerstitial nephropathy or rejection was involved.

Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197.

Vaccines consisting of oligosaccharide (OS) derived from Haemophilus influenzae type b capsular polysaccharide and conjugated to carrier proteins had been shown capable of eliciting memory-type capsular polysaccharide of H. influenza type b antibody responses in human infants, but the structural variables governing immunogenicity were not defined. Here a series of conjugates were made with the diphtheria protein CRM197 and with uniterminally coupled OS haptens that varied in chain length, exposed terminal residue, or multiplicity of loading as defined by ribose/protein ratio. Adults were given a single injection, 1-yr-old infants were given a two-injection sequence, and capsular polysaccharide of H. influenzae type b antibody responses were assessed by radioantigen binding. Vaccines C-4r, C-6r, and C-12r, in which ribitol-ended OS of mean length 4, 6, or 12 repeat units were coupled at low hapten loading, were about equally immunogenic (geometric means 2 to 5 micrograms/ml in infants, 5 to 9 micrograms/ml in adults). Vaccine C7p was made with a higher loading of OS having mean length 7 repeat units and having mainly phosphate monoester at the exposed termini Vaccine C-7R was made from a portion of C-7p by enzymatic removal of most of the terminal phosphates. Compared to the C-4r, C-6r, and C-12r series, vaccines C-7p and C-7R induced geometric means about 10-fold higher in adults and 20-fold higher in infants. Thus OS chain length (in the range studied) and exposed terminus are less critical variables in this system than the extent of hapten loading.

Antibody response of adults to an aluminum hydroxide-adsorbed Neisseria meningitidis serotype 2b protein-group B polysaccharide vaccine.

A group B Neisseria meningitidis serotype protein vaccine was studied clinically in adults. The vaccine comprised lipopolysaccharide-depleted outer membrane vesicles from a serotype 2b strain, 3006-M2, noncovalently complexed with group B meningococcal polysaccharide. Volunteers received 25 micrograms each of protein and polysaccharide administered intramuscularly either in 0.9% NaCl or adsorbed onto aluminum hydroxide on weeks 0 and 6. Most individuals experienced mild local reactions, but there were no systemic reactions. Both vaccine formulations stimulated antibodies to the outer membrane proteins of serotypes 2a:P1.2 and 2b:P1.2, but higher levels were achieved with the aluminum hydroxide-adsorbed vaccine after two immunizations. Vaccine-induced antibodies were primarily IgG and were bactericidal for both a serotype 2a and a serotype 2b strain. Induction of bactericidal antibodies has been shown to be a major predictor of protection against meningococcal disease.

Immunogenicity of the Haemophilus influenzae type b capsular polysaccharide conjugate vaccine in children after systemic Haemophilus influenzae type b infections.

We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.