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1.
Animal ; 17(12): 101027, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38006851

ABSTRACT

Estimating protein fractions and their degradation rate are vital to ensure optimum protein supply and degradation in the digestive system of ruminants. This study investigated the possibility of using the ANKOM gas production system and preserved rumen fluid to estimate the protein fractions and in vitro degradability of protein-rich feeds. Three in vitro methods: (1) gas production method (2) Cornell Net Carbohydrate and Protein System (CNCPS), and (3) the unavailable nitrogen assay of Ross (uNRoss) were used to quantify protein fractions of four feeds (lupin meal, vetch grain, Desmanthus hay, and soybean meal). Rumen fluid mixed with 5% dimethyl sulfoxide and frozen at -20 °C was also compared against fresh rumen fluid in the gas production and uNRoss methods. All three methods ranked the feeds identically in the proportions of available (degradable or 'a + b') protein fractions as vetch grain, soybean meal, lupin meal, and Desmanthus hay in decreasing order. The use of fresh rumen fluid produced greater available protein fractions than preserved rumen fluid in all feeds. However, there was no difference between total gas production from lupin meal and vetch grain fermented for 16 h in either rumen fluid source. The in vitro degradable CP (IVDP) was higher for vetch grain (46 and 70%) at the 4th and 8th hours of incubation than other feeds, whereas soybean meal (85%) exceeded the other feeds after the 16th hour of incubation (P < 0.001). The greatest ammonia-N concentration was from soybean meal (1.27 mg/g) and lupin meal (0.87 mg/g) fermented for four hours using fresh rumen fluid. The proportion of fraction 'b' for soybean (82.1% CP) and lupin meals (39.4% CP) from the CNCPS method were not different (P = 0.001) from the fraction 'b' estimation of the gas production method for the same feeds (r = 0.99). Regardless of the methods, a greater water-soluble protein fraction was found from vetch grain (39.6-46.6% CP), and the proportion of fraction 'c' or unavailable protein in Desmanthus hay (39.1-41.5% CP) exceeded other substrates (P < 0.001). The strong positive correlation between fractions across different methods and identical ranking of feeds suggests the possibility of using ANKOM gas production apparatus for protein fractionation.


Subject(s)
Dietary Proteins , Digestion , Animals , Dietary Proteins/metabolism , Ruminants/metabolism , Glycine max , Nitrogen/metabolism , Rumen/metabolism , Animal Feed/analysis
2.
J Dairy Sci ; 106(11): 7651-7660, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37641268

ABSTRACT

Dry matter intake (DMI) is a primary determinant of milk production in grazing dairy cows and an ability to measure the DMI of individual cows would allow herd managers to formulate supplementary rations that consider the amount of nutrients ingested from grass. The 2 related aims of this experiment were to define the mean number of swallowed boli and mass of the swallowed boli in Holstein-Friesian dairy cattle offered a variety of forages commonly fed in the dairy industry of southeastern Australia, and to evaluate 2 indirect methods for counting the number of swallows. Twelve ruminally-fistulated, lactating Holstein-Friesian cows were randomly assigned to 3 replicated 4 × 4 Latin square designs and offered 4 forages: fresh chicory (FC), fresh perennial ryegrass (RP), alfalfa hay (AH), and perennial ryegrass silage (RS). The experiment was conducted over 28 d with each of 4 periods consisting of 7 d with 3 d of measurement. Forage diets were offered to individual cows following the partial evacuation of the rumen. The first 20 min after forage was offered constituted the measurement period, during which all swallowed boli were manually captured by samplers who placed their hand through the ruminal fistula and over the cardia entrance of the rumen of each cow. Concurrently, microphones and video cameras were used for the indirect measurement of swallows. The average swallowed bolus mass overall was 17.4 g dry matter (DM) per bolus with the lowest mass observed in cows offered FC (8.9 g DM/bolus), followed by RP (14.9 g DM/bolus), compared with cows offered AH (23.6 g DM/bolus) and RS (22.3 g DM/bolus). The swallowing rate was greater in cows offered FC (78 swallows/20 min) than in cows offered RP, AH, and RS (62.3 swallows/20 min). The audio recording method showed greater concordance (Lin's concordance correlation coefficient = 0.90) with the physical capturing of the boli through the rumen, than the video recording method did (Lin's concordance correlation coefficient = 0.54). It is concluded that the mass of the swallowed boli is related to forage type and that using a microphone attached to the cow's forehead can provide an accurate measure of the number of swallows when verified against the actual number of swallows counted by manual interception of the boli at the rumen cardia.

3.
Aquat Toxicol ; 257: 106456, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36889127

ABSTRACT

Toxic species of the dinoflagellate genus Dinophysis can produce diarrheic toxins including okadaic acid (OA) and dinophysistoxins (DTXs), and the non-diarrheic pectenotoxins (PTXs). Okadaic acid and DTXs cause diarrheic shellfish poisoning (DSP) in human consumers, and also cause cytotoxic, immunotoxic and genotoxic effects in a variety of mollusks and fishes at different life stages in vitro. The possible effects of co-produced PTXs or live cells of Dinophysis to aquatic organisms, however, are less understood. Effects on an early life stage of sheepshead minnow (Cyprinodon variegatus), a common finfish in eastern USA estuaries, were evaluated using a 96-h toxicity bioassay. Three-week old larvae were exposed to PTX2 concentrations from 50 to 4000 nM, live Dinophysis acuminata culture (strain DAVA01), live cells resuspended in clean medium or culture filtrate. This D. acuminata strain produced mainly intracellular PTX2 (≈ 21 pg cell-1), with much lower levels of OA and dinophysistoxin-1. No mortality or gill damages were observed in larvae exposed to D. acuminata (from 5 to 5500 cells mL-1), resuspended cells and culture filtrate. However, exposure to purified PTX2 at intermediate to high concentrations (from 250 to 4000 nM) resulted in 8 to 100% mortality after 96 h (24-h LC50 of 1231 nM). Histopathology and transmission electron microscopy of fish exposed to intermediate to high PTX2 concentrations revealed important gill damage, including intercellular edema, necrosis and sloughing of gill respiratory epithelia, and damage to the osmoregulatory epithelium, including hypertrophy, proliferation, redistribution and necrosis of chloride cells. Tissue damage in gills is likely caused by the interaction of PTX2 with the actin cytoskeleton of the affected gill epithelia. Overall, the severe gill pathology observed following the PTX2 exposure suggested death was due to loss of respiratory and osmoregulatory functions in C. variegatus larvae.


Subject(s)
Cyprinidae , Dinoflagellida , Killifishes , Water Pollutants, Chemical , Animals , Humans , Okadaic Acid , Marine Toxins/toxicity , Larva , Water Pollutants, Chemical/toxicity
4.
Int J Implant Dent ; 8(1): 57, 2022 11 22.
Article in English | MEDLINE | ID: mdl-36414824

ABSTRACT

PURPOSE: To assess implant success and survival of immediately placed and restored progressive-type implants in the esthetic zone. MATERIAL AND METHODS: A total of n = 21 patients (21 implants) had received an immediate placement of a tapered, two-part implant with a progressive thread design (PL) for a single tooth replacement in the anterior maxilla. An immediate 'non full-functional loaded' restoration was provided upon adequate primary stability on a final patient-specific abutment (one abutment-one time concept). The final restoration was provided at 12 weeks (baseline). Implant survival and success (e.g. bleeding on probing-BOP, probing pocket depth-PD, mucosal recession-MR, pink esthetic score-PES) as well as patient- reported outcomes (PROM`S) were recorded at 6 and 12 months. RESULTS: An adequate primary implant stability (i.e. insertion torque > 35 Ncm) was obtained at all but one sites. At 12 months, implant survival (n = 20 patients) amounted to 100%. Non-significant changes to baseline were noted for mean BOP (2.5 ± 28.2%), PD (- 0.26 ± 0.73 mm), and MR (0.0 ± 0.4 mm) values. PES values amounted to 12.9 ± 1.14 and 13.2 ± 0.84 at 6 and 12 months. Technical and mechanical complications were not observed. Patients expressed an overall high satisfaction. CONCLUSIONS: The presented immediacy protocol was associated with high survival and success rates on the short-term.


Subject(s)
Dental Implants , Humans , Esthetics, Dental , Prospective Studies , Odontogenesis , Patient Reported Outcome Measures
5.
Int J Obstet Anesth ; 52: 103590, 2022 11.
Article in English | MEDLINE | ID: mdl-36030558

ABSTRACT

BACKGROUND: Lumbar epidural analgesia (LEA) is commonly used for labor analgesia but up to 13% of epidural catheters fail and require replacement. Combined spinal-epidural analgesia is associated with a lower catheter failure rate. Few data exist regarding catheter replacement rates after dural-puncture epidural (DPE). We conducted a retrospective analysis comparing catheter failure rates between epidural and DPE techniques. METHODS: This retrospective single-center trial reviewed all labor neuraxial analgesia procedures among 18 726 women across five years, and identified 810 DPE and 2667 LEA procedures. Catheter failure rates, consisting of replacement or requirement of general anesthesia for cesarean delivery, were compared. Propensity score matching was used to balance the groups. RESULTS: Dural-puncture epidural was associated with significantly fewer catheter failures compared with LEA (74/759 vs. 49/759, odds ratio 0.64, 95% CI 0.44 to 0.93, P=0.02). Sensitivity analysis excluding cases of general anesthesia confirmed this relationship. Risk factors identified for catheter failure included age, body mass index, and nulliparity. Dural-puncture epidural was associated with a longer mean time to catheter replacement (918 min vs. 609 min, P=0.04). Kaplan-Meier and Cox multivariate analyses confirmed this relationship. There was no significant difference in the requirement for epidural analgesia supplementation, but DPE required supplementation significantly later than LEA. There was no difference in the rate of headache or epidural blood patch between groups. CONCLUSIONS: Dural-puncture epidural is associated with fewer catheter failures and replacements than LEA, without an increase in the rate of post-dural puncture headache or epidural blood patch.


Subject(s)
Analgesia, Epidural , Analgesia, Obstetrical , Post-Dural Puncture Headache , Female , Humans , Pregnancy , Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Catheters , Post-Dural Puncture Headache/epidemiology , Post-Dural Puncture Headache/therapy , Post-Dural Puncture Headache/etiology , Punctures , Retrospective Studies
6.
Science ; 372(6547): 1192-1196, 2021 06 11.
Article in English | MEDLINE | ID: mdl-34112691

ABSTRACT

Extending the framework of statistical physics to the nonequilibrium setting has led to the discovery of previously unidentified phases of matter, often catalyzed by periodic driving. However, preventing the runaway heating that is associated with driving a strongly interacting quantum system remains a challenge in the investigation of these newly discovered phases. In this work, we utilize a trapped-ion quantum simulator to observe the signatures of a nonequilibrium driven phase without disorder-the prethermal discrete time crystal. Here, the heating problem is circumvented not by disorder-induced many-body localization, but rather by high-frequency driving, which leads to an expansive time window where nonequilibrium phases can emerge. Floquet prethermalization is thus presented as a general strategy for creating, stabilizing, and studying intrinsically out-of-equilibrium phases of matter.

7.
Int J Obstet Anesth ; 45: 49-55, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33293185

ABSTRACT

BACKGROUND: Intravenous dexmedetomidine 30 µg reduces shivering after cesarean delivery but can result in sedation and dry mouth. We hypothesized that prophylactic administration of 10 µg of IV dexmedetomidine would reduce the patient-reported severity of shivering after cesarean delivery, without an increased incidence of side effects. METHODS: After institutional review board approval and informed written consent, women undergoing scheduled cesarean delivery with spinal or combined spinal-epidural anesthesia were randomized to receive either intravenous normal saline or dexmedetomidine 10 µg immediately after delivery. The primary outcome was a patient-rated subjective shivering score using a 10-cm visual analog scale at 30 and 60 min after arrival in the Post-Anesthesia Care Unit. Secondary outcomes included subjective scores for pain, nausea, itching, dry mouth, and sedation, as well as 24-h medication administration and investigator-rated observations of shivering, vomiting, pruritus, and sedation. Repeated measures ANOVA with Tukey-Kramer multiple-comparison test was applied for primary outcomes. RESULTS: One hundred patients were enrolled, and 85 completed the study and were included in analysis. The mean ±â€¯SD shivering score in the dexmedetomidine group was significantly lower by repeated measures analysis than among controls across the first 60 min (P=0.0002), and individually at both 30 and 60 min (placebo 1.8 ±â€¯2.6 vs. dexmedetomidine 0.6 ±â€¯1.4 at 30 min; 1.2 ±â€¯2.1 vs. 0.3 ±â€¯0.6 at 60 min; both P <0.01). Patient-rated and observer-rated side effects did not significantly differ between groups. CONCLUSIONS: Prophylactic administration of intravenous dexmedetomidine 10 µg after delivery reduces shivering without notable side effects.


Subject(s)
Anesthesia, Spinal , Dexmedetomidine , Double-Blind Method , Female , Humans , Pregnancy , Prospective Studies , Shivering
8.
Int J Obstet Anesth ; 42: 57-60, 2020 05.
Article in English | MEDLINE | ID: mdl-31791878

ABSTRACT

BACKGROUND: Evidence to guide clinical decision-making in pregnant women who are usually asymptomatic, but identified as heterozygote carriers of F11 mutations, is lacking. We hypothesized that women identified on prenatal screening as heterozygous for a mutation in the F11 allele would have minimal evidence of an in vitro coagulation abnormality. METHODS: We prospectively enrolled women identified by prenatal screening as F11 mutation carriers and pregnant women who were presumed to be normal as controls. We collected blood during antepartum visits or at presentation for delivery and assessed Factor XI (FXI) coagulant activity level, as well as whole-blood coagulation, by thromboelastography. RESULTS: F11 mutation carriers had lower serum FXI activity levels than controls (51.2 ±â€¯8.5% vs 94.1 ±â€¯19.4%; P <0.0001). Thromboelastography values of all control subjects and F11 mutation carriers were within the normal range. The R-time was slightly longer in F11 mutation carriers (5.3 ±â€¯1.0 s vs 4.2 ±â€¯0.8 s, P <0.002), but no other statistically significant differences in thromboelastogram parameters were identified between groups. CONCLUSIONS: Despite lower FXI activity in the F11 mutation group, we found minimal differences in whole-blood measures of coagulation using thromboelastography. These findings support our hypothesis that a single copy of an F11 mutation does not produce significant evidence of an in vitro coagulation abnormality. Thromboelastography might be useful in determining the risk of neuraxial anesthesia in pregnant women, but additional work is required to establish the validity of this test.


Subject(s)
Blood Coagulation/genetics , Blood Coagulation/physiology , Factor XI/genetics , Heterozygote , Mutation/genetics , Thrombelastography/methods , Adult , Female , Humans , Pregnancy , Prospective Studies
9.
Nature ; 576(7786): 232-236, 2019 12.
Article in English | MEDLINE | ID: mdl-31802002

ABSTRACT

Remote observations of the solar photospheric light scattered by electrons (the K-corona) and dust (the F-corona or zodiacal light) have been made from the ground during eclipses1 and from space at distances as small as 0.3 astronomical units2-5 to the Sun. Previous observations6-8 of dust scattering have not confirmed the existence of the theoretically predicted dust-free zone near the Sun9-11. The transient nature of the corona has been well characterized for large events, but questions still remain (for example, about the initiation of the corona12 and the production of solar energetic particles13) and for small events even its structure is uncertain14. Here we report imaging of the solar corona15 during the first two perihelion passes (0.16-0.25 astronomical units) of the Parker Solar Probe spacecraft13, each lasting ten days. The view from these distances is qualitatively similar to the historical views from ground and space, but there are some notable differences. At short elongations, we observe a decrease in the intensity of the F-coronal intensity, which is suggestive of the long-sought dust free zone9-11. We also resolve the fine-scale plasma structure of very small eruptions, which are frequently ejected from the Sun. These take two forms: the frequently observed magnetic flux ropes12,16 and the predicted, but not yet observed, magnetic islands17,18 arising from the tearing-mode instability in the current sheet. Our observations of the coronal streamer evolution confirm the large-scale topology of the solar corona, but also reveal that, as recently predicted19, streamers are composed of yet smaller substreamers channelling continual density fluctuations at all visible scales.

10.
J Dairy Sci ; 102(3): 2714-2723, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30660414

ABSTRACT

Diets that contain high proportions of either wheat or supplementary fat have been individually reported to reduce enteric methane production. The objective of this research was to determine the effect of dietary fat supplementation on methane emissions and milk yield from cows fed diets containing either corn or wheat grains. It was hypothesized that cows fed a diet containing wheat would produce less methane and have lower methane yield (methane per kg of dry matter intake; MY) than cows fed a diet containing corn and that methane mitigation from fat supplementation would occur irrespective of the type of grain in the basal diet. The experiment involved 32 Holstein-Friesian dairy cows allocated to 1 of 4 treatment groups (n = 8) and individually fed different diets restricted to approximately 90% of their mean ad libitum intake measured during a covariate period. All animals were offered 11.5 kg of dry matter/d of alfalfa hay, 1.8 kg of dry matter/d of solvent-extracted canola meal, and 1 of 4 dietary supplements. Dietary supplements were 8 kg of dry matter/d of either corn or wheat, or these same treatments with the addition of 0.8 kg of canola oil. In this 5-wk experiment, d 1 to 7 served as the covariate period, d 8 to 14 as the transition period, d 15 to 28 as the adaptation period, and d 29 to 35 as the experimental period. Cows were fed their full treatment diets from d 15 to 35 during which time milk production and feed intake were measured daily. During d 29 to 35, methane production was measured for individual cows daily using the sulfur hexafluoride tracer method. The resulting averages for milk production and feed intake were analyzed by analysis of covariance with factorial grain by fat as treatment structure, animal as the unit within blocks, and the corresponding milk production or feed intake covariate averages as principal covariate. Data on milk fatty acids, ruminal fluid data on pH, ammonia, volatile fatty acids, protozoa, and methane were analyzed by ANOVA using the same treatment and blocking structures excluding the principal covariate. Cows fed a diet containing wheat had greater MY than cows fed a diet containing corn. Irrespective of the type of grain in the diet, increasing the fat concentration from 2 to 6% dry matter reduced MY. It is concluded that the grain component in the basal diet does not affect the mitigating effects of dietary fat supplements on MY.


Subject(s)
Cattle , Dietary Fats/pharmacology , Dietary Supplements , Methane/metabolism , Triticum , Zea mays , Animals , Dairying , Diet/veterinary , Edible Grain , Fatty Acids/analysis , Female , Lactation , Milk/chemistry , Poaceae
11.
Space Weather ; 16(7): 784-801, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30147630

ABSTRACT

The Solar TErrestrial RElations Observatory (STEREO) and its heliospheric imagers (HIs) have provided us the possibility to enhance our understanding of the interplanetary propagation of coronal mass ejections (CMEs). HI-based methods are able to forecast arrival times and speeds at any target and use the advantage of tracing a CME's path of propagation up to 1 AU and beyond. In our study, we use the ELEvoHI model for CME arrival prediction together with an ensemble approach to derive uncertainties in the modeled arrival time and impact speed. The CME from 3 November 2010 is analyzed by performing 339 model runs that are compared to in situ measurements from lined-up spacecraft MErcury Surface, Space ENvironment, GEochemistry, and Ranging and STEREO-B. Remote data from STEREO-B showed the CME as halo event, which is comparable to an HI observer situated at L1 and observing an Earth-directed CME. A promising and easy approach is found by using the frequency distributions of four ELEvoHI output parameters, drag parameter, background solar wind speed, initial distance, and speed. In this case study, the most frequent values of these outputs lead to the predictions with the smallest errors. Restricting the ensemble to those runs, we are able to reduce the mean absolute arrival time error from 3.5 ± 2.6 to 1.6 ± 1.1 hr at 1 AU. Our study suggests that L1 may provide a sufficient vantage point for an Earth-directed CME, when observed by HI, and that ensemble modeling could be a feasible approach to use ELEvoHI operationally.

12.
J Dairy Sci ; 101(8): 7117-7132, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29729908

ABSTRACT

Short-term studies have shown that feeding dairy cows diets containing a high proportion (>40%) of wheat may result in reduced milk fat concentration and reduced CH4 emissions (g of CH4/cow per d), but no long-term studies have been done on these responses. This study compared the milk production and CH4 responses when 24 dairy cows were fed diets containing high proportions of either wheat or corn over 16 wk. Cows were assigned to 2 groups and offered a diet (CRN) containing 10.0 kg of dry matter/d of crushed corn grain, 1.8 kg of dry matter/d of canola meal, 0.2 kg of dry matter/d of minerals, and 11.0 kg of dry matter/d of chopped alfalfa hay or a similar diet (WHT) in which wheat replaced the corn. Dry matter intake and milk yields of individual cows were measured daily. Methane emissions from individual cows were measured using controlled climate respiration chambers over 2 consecutive days during each of wk 4, 10, and 16. Milk composition was measured on the 2 d when cows were in chambers during wk 4, 10, and 16. Over the 16-wk experimental period, total dry matter intake remained relatively constant and similar for the 2 dietary treatment groups. At wk 4, CH4 emission, CH4 yield (g of CH4/kg of dry matter intake), milk fat yield, and milk fat concentration were substantially less in cows fed the WHT diet compared with the same metrics in cows fed the CRN diet; but these differences were not apparent at wk 10 and 16. The responses over time in these metrics were not similar in all cows. In 4 cows fed the WHT diet, CH4 yield, milk fat concentration, and milk fat yield remained relatively constant from wk 4 to 16, whereas for 5 fed the WHT diet, their CH4 emissions, milk fat yields, and milk fat concentrations almost doubled between wk 4 and 16. In the short term (4 wk), the inclusion of approximately 45% wheat instead of corn in the diet of cows resulted in reductions of 39% in CH4 yield, 35% in milk fat concentration, and 40% in milk fat yield. However, these reductions did not persist to wk 10 or beyond. Our data indicate that cows do not all respond in the same way with some "adaptive" cows showing a marked increase in CH4 yield, milk fat concentration, and milk fat yield after wk 4, whereas in other "nonadaptive" cows, these metrics were persistently inhibited to 16 wk. This research shows that short-term studies on dietary interventions to mitigate enteric CH4 emissions may not always predict the long-term effects of such interventions.


Subject(s)
Cattle/metabolism , Methane/biosynthesis , Milk/chemistry , Triticum , Animals , Diet , Female , Lactation , Rumen/metabolism , Zea mays
13.
Vet Comp Oncol ; 16(1): E123-E129, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28941072

ABSTRACT

Oral melphalan has been included in multi-agent rescue protocols for canine lymphoma but its activity as a single-agent for this purpose has not been established. Inexpensive cost, ease of administration and tolerability make oral melphalan an attractive candidate for single-agent rescue therapy of canine lymphoma. Retrospective evaluation of 19 cases of relapsed canine lymphoma treated with oral melphalan was performed. Melphalan was primarily administered (n = 16) via a high dose protocol (HDM) with a median dosage of 19.4 mg m-2 . Fifteen dogs (78.9%) were treated concurrently with corticosteroids. Response evaluation was possible for all dogs with a calculated overall clinical benefit (partial response [PR] + stable disease [SD]) of 31.6% (PR 3/19; SD 3/19). Times to progression following melphalan (TTP-M) were 14, 24 and 34 days for responders and 20, 28 and 103 days for dogs experiencing SD. Twelve of 17 dogs evaluable for toxicity experienced an adverse event (AE) with only 3 dogs experiencing a grade III or higher AE. Haematologic toxicity was common (11/17) while gastrointestinal toxicity was rare (1/17). Although treatment resulted in limited clinical benefit and non-durable responses, oral melphalan was well-tolerated and may be a reasonable rescue option in cases where minimal effective agents remain.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dog Diseases/drug therapy , Lymphoma/veterinary , Melphalan/therapeutic use , Administration, Oral , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Dogs , Female , Lymphoma/drug therapy , Male , Melphalan/administration & dosage , Melphalan/adverse effects , Recurrence , Retrospective Studies
14.
Toxicol Lett ; 282: 136-146, 2018 Jan 05.
Article in English | MEDLINE | ID: mdl-29107028

ABSTRACT

Azaspiracids (AZAs) are marine algal toxins that can be accumulated by edible shellfish to cause a foodborne gastrointestinal poisoning in humans. In the European Union, only AZA1, -2 and -3 are currently regulated and their concentration in shellfish is determined through their toxic equivalency factors (TEFs) derived from the intraperitoneal lethal potency in mice. Nevertheless, considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data. Thus, the acute oral toxicity of AZA1, -2 and -3 was investigated in female CD-1 mice treated with different doses (AZA1: 135-1100µg/kg; AZA2 and AZA3: 300-1100µg/kg) and sacrificed after 24h or 14days. TEFs derived from the median lethal doses (LD50) were 1.0, 0.7 and 0.5, respectively for AZA1, -2 and -3. In fact, after 24h from gavage administration, LD50s were 443µg/kg (AZA1; 95% CL: 350-561µg/kg), 626µg/kg (AZA2; 95% CL: 430-911µg/kg) and 875µg/kg (AZA3; 95% CL: 757-1010µg/kg). Mice dead more than 5h after the treatment or those sacrificed after 24h (doses: ≥175µg AZA1/kg, ≥500µg AZA2/kg and ≥600µg AZA3/kg) showed enlarged pale liver, while increased serum markers of liver alteration were recorded even at the lowest doses. Blood chemistry revealed significantly increased serum levels of K+ ions (≥500mg/kg), whereas light microscopy showed tissue changes in the gastrointestinal tract, liver and spleen. No lethality, macroscopic, tissue or haematological changes were recorded two weeks post exposure, indicating reversible toxic effects. LC-MS/MS analysis of the main organs showed a dose-dependency in gastrointestinal absorption of these toxins: at 24h, the highest levels were detected in the stomach and, in descending order, in the intestinal content, liver, small intestine, kidneys, lungs, large intestine, heart as well as detectable traces in the brain. After 14days, AZA1 and AZA2 were still detectable in almost all the organs and intestinal content.


Subject(s)
Furans/toxicity , Marine Toxins/toxicity , Pyrans/toxicity , Spiro Compounds/toxicity , Administration, Oral , Animals , Dose-Response Relationship, Drug , Female , Furans/pharmacokinetics , Lethal Dose 50 , Marine Toxins/pharmacokinetics , Mice, Inbred Strains , Mytilus edulis/chemistry , Organ Specificity , Pyrans/pharmacokinetics , Spiro Compounds/pharmacokinetics , Tissue Distribution , Toxicity Tests, Acute
15.
Nature ; 551(7682): 601-604, 2017 11 29.
Article in English | MEDLINE | ID: mdl-29189781

ABSTRACT

A quantum simulator is a type of quantum computer that controls the interactions between quantum bits (or qubits) in a way that can be mapped to certain quantum many-body problems. As it becomes possible to exert more control over larger numbers of qubits, such simulators will be able to tackle a wider range of problems, such as materials design and molecular modelling, with the ultimate limit being a universal quantum computer that can solve general classes of hard problems. Here we use a quantum simulator composed of up to 53 qubits to study non-equilibrium dynamics in the transverse-field Ising model with long-range interactions. We observe a dynamical phase transition after a sudden change of the Hamiltonian, in a regime in which conventional statistical mechanics does not apply. The qubits are represented by the spins of trapped ions, which can be prepared in various initial pure states. We apply a global long-range Ising interaction with controllable strength and range, and measure each individual qubit with an efficiency of nearly 99 per cent. Such high efficiency means that arbitrary many-body correlations between qubits can be measured in a single shot, enabling the dynamical phase transition to be probed directly and revealing computationally intractable features that rely on the long-range interactions and high connectivity between qubits.

16.
Philos Trans A Math Phys Eng Sci ; 375(2108)2017 Dec 13.
Article in English | MEDLINE | ID: mdl-29084886

ABSTRACT

Linear arrays of trapped and laser-cooled atomic ions are a versatile platform for studying strongly interacting many-body quantum systems. Effective spins are encoded in long-lived electronic levels of each ion and made to interact through laser-mediated optical dipole forces. The advantages of experiments with cold trapped ions, including high spatio-temporal resolution, decoupling from the external environment and control over the system Hamiltonian, are used to measure quantum effects not always accessible in natural condensed matter samples. In this review, we highlight recent work using trapped ions to explore a variety of non-ergodic phenomena in long-range interacting spin models, effects that are heralded by the memory of out-of-equilibrium initial conditions. We observe long-lived memory in static magnetizations for quenched many-body localization and prethermalization, while memory is preserved in the periodic oscillations of a driven discrete time crystal state.This article is part of the themed issue 'Breakdown of ergodicity in quantum systems: from solids to synthetic matter'.

17.
Int J Obstet Anesth ; 32: 54-63, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28684143

ABSTRACT

Each calendar year the Society for Obstetric Anesthesia and Perinatology invites an individual to conduct a review of the medical literature, identifying clinically relevant publications of interest to the obstetric anesthesia provider. This report of that effort covers the publications from 2015 and includes the categories of anesthesia and analgesia, complications of neuraxial procedures, and the effects of anesthesia on the fetus. Neuraxial procedures represent the foundation of obstetric anesthesia; advances in anesthesia and analgesia include novel modes of administration, and refinements in care of the medically complex patient. In addition to labor analgesia, investigations into post-cesarean recovery address challenges in pain control, patients with obstructive sleep apnea, and treatment protocols intended to improve patient care, notably an enhanced-recovery pathway. Because complications are inevitable, this review identifies investigations on the more common complications of neuraxial procedures, such as hypotension, maternal and fetal bradycardia, and post-dural puncture headache. There were several innovative reports attempting to address these complications, including the use of norepinephrine infusion for the prevention of spinal-induced hypotension, ephedrine for the prevention of fetal bradycardia after combined spinal-epidural analgesia, and pharmacologic treatment of post-dural puncture headache. Not all of these treatments were successful. Finally, there are potential effects of anesthesia on the fetal/neonatal brain, much of which remains poorly defined. An analysis of recent papers suggests that epidural fever is not an independent cause of adverse neurologic fetal injury. On the other hand, evidence continues to grow to support the hypothesis that anesthetic drugs impact neonatal neurologic outcome.


Subject(s)
Anesthesia, Obstetrical , Analgesia, Obstetrical , Anesthesia, Epidural/adverse effects , Anesthesia, Obstetrical/adverse effects , Anesthesia, Spinal/adverse effects , Cesarean Section , Female , Humans , Norepinephrine/therapeutic use , Pregnancy
18.
Nature ; 543(7644): 217-220, 2017 03 08.
Article in English | MEDLINE | ID: mdl-28277505

ABSTRACT

Spontaneous symmetry breaking is a fundamental concept in many areas of physics, including cosmology, particle physics and condensed matter. An example is the breaking of spatial translational symmetry, which underlies the formation of crystals and the phase transition from liquid to solid. Using the analogy of crystals in space, the breaking of translational symmetry in time and the emergence of a 'time crystal' was recently proposed, but was later shown to be forbidden in thermal equilibrium. However, non-equilibrium Floquet systems, which are subject to a periodic drive, can exhibit persistent time correlations at an emergent subharmonic frequency. This new phase of matter has been dubbed a 'discrete time crystal'. Here we present the experimental observation of a discrete time crystal, in an interacting spin chain of trapped atomic ions. We apply a periodic Hamiltonian to the system under many-body localization conditions, and observe a subharmonic temporal response that is robust to external perturbations. The observation of such a time crystal opens the door to the study of systems with long-range spatio-temporal correlations and novel phases of matter that emerge under intrinsically non-equilibrium conditions.

19.
Vet Comp Oncol ; 15(3): 1101-1114, 2017 Sep.
Article in English | MEDLINE | ID: mdl-27402031

ABSTRACT

Acute leukaemia (AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose-intense chemotherapy, more human patients attain long-term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty-six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9-218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1-300). Untreated (n = 6) and palliatively-treated (n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short.


Subject(s)
Dog Diseases/drug therapy , Leukemia/veterinary , Acute Disease , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Dog Diseases/mortality , Dogs , Leukemia/drug therapy , Leukemia/mortality , Retrospective Studies , Survival Analysis , Treatment Outcome
20.
Vet Comp Oncol ; 13(2): 77-88, 2015 Jun.
Article in English | MEDLINE | ID: mdl-23253146

ABSTRACT

Resistance to Escherichia coli l-asparaginase in canine lymphoma occurs frequently with repeated administration, a phenomenon often attributed, without substantiation, to the induction of neutralizing antibodies. To test the hypothesis that treated dogs develop antibodies against the drug, we created an enzyme-linked immunosorbent assay (ELISA) to measure plasma anti-asparaginase immunoglobulin G responses. Using samples from dogs that had received multiple doses, specific reactivity against l-asparaginase was demonstrated, while naïve patients' samples were negative. The optimized ELISA appeared sensitive, with endpoint titers >1 600 000 in positive control dogs. Intra- and inter-assay coefficients of variation were 3.6 and 14.5%. The assay was supported by the observation that ELISA-positive plasma could immunoprecipitate asparaginase activity. When clinical patients were evaluated, 3/10 dogs developed titers after a single injection; with repeated administration, 4/7 dogs were positive. l-asparaginase antibodies showed reduced binding to the PEGylated drug formulation. The ELISA should prove useful in investigating the potential correlation of antibody responses with resistance.


Subject(s)
Antibodies/blood , Antineoplastic Agents/therapeutic use , Asparaginase/therapeutic use , Dog Diseases/drug therapy , Escherichia coli/enzymology , Lymphoma/veterinary , Animals , Antineoplastic Agents/immunology , Asparaginase/immunology , Dog Diseases/blood , Dog Diseases/immunology , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Immunoglobulin G/blood , Lymphoma/blood , Lymphoma/drug therapy , Lymphoma/immunology , Reproducibility of Results , Sensitivity and Specificity
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