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1.
J Infect ; 81(3): 411-419, 2020 09.
Article in English | MEDLINE | ID: mdl-32504743

ABSTRACT

OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22-31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70-336) compared with previous years. Systematic testing identified 40% (95% CI 35-46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34-52) were asymptomatic and 18% (95% CI 11-24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or had no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Nursing Homes , Pneumonia, Viral/pathology , Aged , Aged, 80 and over , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Female , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , SARS-CoV-2 , Time Factors , United Kingdom/epidemiology
2.
Environ Sci Pollut Res Int ; 23(21): 22212-22217, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27662863

ABSTRACT

The length of time cadmium (Cd) is in contact with the soil has been recognised as a factor affecting phytoavailability, but the extent of this process is currently poorly understood. This study used isotopic dilution techniques (E and L values) to determine the effect of contact time on Cd phytoavailability from soil collected from a long-term phosphorus (P) fertiliser trial. Cadmium phytoavailability was determined in soil that was last fertilised with soluble Cd from P fertiliser 17 years prior to sampling (residual plots) and soil that received annual applications of P fertiliser until sampling (continuous plots). It was found that both E values and L values increased with P fertiliser (viz Cd) inputs and were significantly related to each other (r 2 = 0.82 P < 0.005). There was however no significant difference (P < 0.05) in the percentage of total Cd that was phytoavailable calculated using E values (E%) between the continuous (mean 51 %) and the residual plots (mean 51 %). There was also no significant difference (P < 0.05) in the percentage of total soil Cd that was phytoavailable calculated using L values (L%) between the continuous (mean 77 %) and residual plots (mean 87 %). These results suggest that despite Cd being in contact with the soil for 17 years, there was no difference in the size of the phytoavailable Cd pool compared to recent Cd inputs. This study should be repeated for other soil types and factored into any analysis for the long-term implications of ongoing Cd accumulation in soil on future landuse.


Subject(s)
Cadmium/metabolism , Fertilizers/analysis , Plants/metabolism , Soil Pollutants/metabolism , Biological Availability , New Zealand , Phosphorus/analysis , Soil/chemistry , Time Factors
3.
Neuropsychology ; 30(8): 915-919, 2016 11.
Article in English | MEDLINE | ID: mdl-27442451

ABSTRACT

OBJECTIVE: Generalization is the application of existing knowledge to novel situations. Questions remain about the precise role of the hippocampus in this facet of learning, but a connectionist model by Gluck and Myers (1993) predicts that generalization should be enhanced following hippocampal damage. METHOD: In a two-category learning task, a group of amnesic patients (n = 9) learned the training items to a similar level of accuracy as matched controls (n = 9). Both groups then classified new items at various levels of distortion. RESULTS: The amnesic group showed significantly more accurate generalization to high-distortion novel items, a difference also present compared to a larger group of unmatched controls (n = 33). CONCLUSIONS: The model prediction of a broadening of generalization gradients in amnesia, at least for items near category boundaries, was supported by the results. Our study shows for the first time that amnesia can sometimes improve generalization. (PsycINFO Database Record


Subject(s)
Amnesia/diagnosis , Amnesia/physiopathology , Amnesia/psychology , Color Perception/physiology , Generalization, Stimulus/physiology , Hippocampus/physiopathology , Pattern Recognition, Visual/physiology , Adult , Brain Damage, Chronic/diagnosis , Brain Damage, Chronic/physiopathology , Brain Damage, Chronic/psychology , Dominance, Cerebral/physiology , Female , Humans , Hypoxia, Brain/diagnosis , Hypoxia, Brain/physiopathology , Hypoxia, Brain/psychology , Magnetic Resonance Imaging , Male , Middle Aged
4.
Neurobiol Learn Mem ; 108: 185-95, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24096204

ABSTRACT

We review evidence that supports the conclusion that people can and do learn in two distinct ways - one associative, the other propositional. No one disputes that we solve problems by testing hypotheses and inducing underlying rules, so the issue amounts to deciding whether there is evidence that we (and other animals) also rely on a simpler, associative system, that detects the frequency of occurrence of different events in our environment and the contingencies between them. There is neuroscientific evidence that associative learning occurs in at least some animals (e.g., Aplysia californica), so it must be the case that associative learning has evolved. Since both associative and propositional theories can in principle account for many instances of successful learning, the problem is then to show that there are at least some cases where the two classes of theory predict different outcomes. We offer a demonstration of cue competition effects in humans under incidental conditions as evidence against the argument that all such effects are based on cognitive inference. The latter supposition would imply that if the necessary information is unavailable to inference then no cue competition should occur. We then discuss the case of unblocking by reinforcer omission, where associative theory predicts an irrational solution to the problem, and consider the phenomenon of the Perruchet effect, in which conscious expectancy and conditioned response dissociate. Further discussion makes use of evidence that people will sometimes provide one solution to a problem when it is presented to them in summary form, and another when they are presented in rapid succession with trial-by trial information. We also demonstrate that people trained on a discrimination may show a peak shift (predicted by associative theory), but given the time and opportunity to detect the relationships between S+ and S-, show rule-based behavior instead. Finally, we conclude by presenting evidence that research on individual differences suggests that variation in intelligence and explicit problem solving ability are quite unrelated to variation in implicit (associative) learning, and briefly consider the computational implications of our argument, by asking how both associative and propositional processes can be accommodated within a single framework for cognition.


Subject(s)
Association Learning , Cognition , Learning , Models, Psychological , Animals , Cues , Humans , Mental Processes
5.
J Exp Psychol Anim Behav Process ; 39(2): 166-73, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23586537

ABSTRACT

This research explored the role that associative learning may play in human sequence learning. Two-choice serial reaction time tasks were performed under incidental conditions using 2 different sequences. In both cases, an experimental group was trained on 4 subsequences: LLL, LRL, RLR, and RRR for Group "Same" and LLR, LRR, RLL, and RRL for Group "Different," with left and right counterbalanced across participants. To control for sequential effects, we assayed sequence learning by comparing their performance with that of a control group, which had been trained on a pseudorandom ordering, during a test phase in which both experimental and control groups experienced the same subsequences. Participants in both groups showed sequence learning, but the group trained on "different" learned more and more rapidly. This result is the opposite that predicted by the augmented simple recurrent network used by F. W. Jones and I. P. L. McLaren (2009, Human sequence learning under incidental and intentional conditions, Journal of Experimental Psychology: Animal Behavior Processes, Vol. 35, pp. 538-553), but can be modeled using a reparameterized version of this network that also includes a more realistic representation of the stimulus array, suggesting that the latter may be a better model of human sequence learning under incidental conditions.


Subject(s)
Choice Behavior/physiology , Models, Psychological , Serial Learning/physiology , Space Perception/physiology , Adolescent , Adult , Female , Humans , Intention , Male , Reaction Time/physiology , Young Adult
6.
Learn Behav ; 40(3): 320-33, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22927004

ABSTRACT

In this article, we present our first attempt at combining an elemental theory designed to model representation development in an associative system (based on McLaren, Kaye, & Mackintosh, 1989) with a configural theory that models associative learning and memory (McLaren, 1993). After considering the possible advantages of such a combination (and some possible pitfalls), we offer a hybrid model that allows both components to produce the phenomena that they are capable of without introducing unwanted interactions. We then successfully apply the model to a range of phenomena, including latent inhibition, perceptual learning, the Espinet effect, and first- and second-order retrospective revaluation. In some cases, we present new data for comparison with our model's predictions. In all cases, the model replicates the pattern observed in our experimental results. We conclude that this line of development is a promising one for arriving at general theories of associative learning and memory.


Subject(s)
Association Learning , Models, Psychological , Psychological Theory , Animals , Computer Simulation/statistics & numerical data , Conditioning, Classical , Discrimination Learning , Humans , Inhibition, Psychological , Memory
7.
J Exp Psychol Anim Behav Process ; 38(2): 203-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22250788

ABSTRACT

Is human Pavlovian conditioning driven by a unitary, propositional system (as claimed by Mitchell, De Houwer, & Lovibond, 2009) or by dual systems; one under conscious control, symbolic in nature, and requiring effort to deploy, and the other utilizing associative processes and automatic in its operation (McLaren, Green, & Mackintosh, 1994)? Past research has suggested that for electrodermal conditioning to occur in humans, conscious awareness of the contingencies is necessary to produce conditioned responding (e.g., Hinchy, Lovibond, & Ter-Horst, 1995), as predicted by single process theories that attribute the conditioned response (CR) to conscious expectancy of the shock. In this article, the authors examined the Perruchet effect (Perruchet, 1985), using an electrodermal paradigm to determine whether there is any role for associative processes in human electrodermal conditioning. The authors attempted to replicate the basic effect, whereby expectancy of an unconditioned stimulus (US) increases over a run of nonreinforced trials while the CR to the conditional stimulus (CS) declines, and the complementary pattern in which expectancy decreases over a run of reinforced trials while the CR to the CS grows in strength. In line with these patterns, the change in skin conductance response (our CR) as a function of US run length was found to follow a linear trend opposite to that of conscious expectancy of shock with respect to US run length. This dissociation supports a dual-processing system account of human Pavlovian conditioning, with conscious, controlled processes governing expectancy (and subject to the gambler's fallacy), whereas automatic, associative processes determine at least some of the strength of the CR to the CS.


Subject(s)
Association Learning/physiology , Conditioning, Classical , Consciousness/physiology , Galvanic Skin Response , Adolescent , Adult , Attention , Female , Humans , Male , Photic Stimulation , Time Factors , Young Adult
9.
J Anim Sci ; 87(6): 1856-64, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19251921

ABSTRACT

This work investigated effects of carrying 0, 1, or 2 copies of the A allele resulting from the g+6723G-A transition in growth differentiation factor gene (GDF8) in New Zealand Texel-cross sheep at different lamb ages and carcass weights. Two Texel-cross sires carrying 1 copy of the A allele were mated to approximately 200 ewes carrying 0, 1, or 2 copies of the A allele. A total of 187 progeny were generated and genotyped to determine whether they were carrying 0, 1, or 2 copies of the A allele. The progeny were assigned to 1 of 4 slaughter groups balanced for the 3 genotypes, sex, and sire. The 4 groups were slaughtered commercially when their average BW (across all progeny in the slaughter group) reached 33, 40, 43, and 48 kg, respectively. Measurements of BW, and carcass dimensions and yield were made on all animals using Viascan (a commercial 2-dimensional imaging system that estimates lean content of the carcass as a percentage of total carcass weight). Additional measurements were made on the fourth slaughter group, which was computed tomography scanned at each slaughter time point to obtain 4 serial measures of lean and fat as estimated from the computed tomography images. The A allele did not have an effect on any BW traits. The A allele was associated with increased muscle and decreased fat across the variety of measures of muscling and fat, explaining between 0.2 and 1.1 of a residual SD unit. Estimates for an additive effect were significant and were positive for muscle and negative for fat traits. No dominance effect estimates (positive or negative) were significant. There was no significant interaction between A allele number and carcass weight or slaughter group for any trait. This is the first systematic study of the effect of the A allele copy number over a range of carcass weights (13 to 20 kg) and ages and results suggest the size of the effect across these endpoints is proportionately the same. Testing for the A allele therefore offers breeders the potential to improve rates of genetic gain for lean-meat yield across most production systems.


Subject(s)
Body Composition/genetics , Myostatin/genetics , Polymorphism, Single Nucleotide , Sheep/genetics , Sheep/physiology , Animals , Body Composition/physiology , Body Weight/genetics , Body Weight/physiology , Breeding , Female , Haplotypes , Male , Muscle, Skeletal/physiology
10.
Animal ; 3(2): 189-99, 2009 Feb.
Article in English | MEDLINE | ID: mdl-22444221

ABSTRACT

Texel muscling quantitative trait locus (TM-QTL) is a QTL on chromosome 18, originally identified in purebred UK Texel sheep, which was reported to increase ultrasonically measured muscle depth at the third lumbar vertebra by around 4% to 7%. The objective of the present study was to comprehensively evaluate the TM-QTL and to determine whether it could provide benefits to the UK sheep industry through increased carcass meat yield in crossbred slaughter lambs. Effects of this QTL on a range of carcass traits, including those measured in vivo and by dissection, were evaluated in heterozygous carrier and non-carrier lambs produced by crossing heterozygous carrier Texel rams with non-carrier Mule (Bluefaced Leicester × Scottish Blackface) ewes from a lowland flock. The TM-QTL was found to increase loin muscling in crossbred lambs at a given live weight or carcass weight, as measured by ultrasound, X-ray computed tomography (CT) and carcass dissection. Depth of M. longissimus lumborum (MLL) was greater in TM-QTL carrier lambs compared to non-carriers as measured by both ultrasound at the third lumbar vertebra (+4.5%; P = 0.033) and CT scanning at the fifth lumbar vertebra (+6.7%; P = 0.004). Width and area of MLL measured using CT were also greater in TM-QTL carrier lambs compared to non-carriers (+3.0%; P = 0.013 and +5.1%; P = 0.047, respectively). Loin muscle volume measured using CT was greater in TM-QTL carriers than in non-carriers (+5.9%; P = 0.005) and the dissected weight of the MLL was +7.1% greater in TM-QTL carriers compared to non-carriers (P < 0.001). The proportion of the total carcass lean meat yield (LMY) that was contained within the loin region was slightly higher in TM-QTL carriers than in non-carriers (0.154 v. 0.145; P = 0.006). However, TM-QTL was found to have no significant effect on the total weight or proportion of LMY or of saleable meat yield in the carcass measured by dissection, or on muscling in the hind leg measured by CT or dissection. This work has verified that the inheritance of TM-QTL is associated with increased loin muscling in crossbred lambs, as has previously been reported for purebred Texel lambs.

11.
Clin Orthop Relat Res ; 466(6): 1372-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18340503

ABSTRACT

Elution of antibiotics from antibiotic-loaded polymethylmethacrylate (AL-PMMA) increases when soluble particulate filler is added to increase the permeability of the PMMA. Antibiotic powder is in itself soluble particulate filler. For greater volume fractions of filler, greater elution occurs. The volume of generic tobramycin powder is more than 3.5 times the volume of proprietary tobramycin powder for a 1.2 g dose leading to the question: Does generic tobramycin elute from AL-PMMA faster than proprietary tobramycin? We performed elution studies on AL-PMMA beads made with 1.2 g of either generic tobramycin or proprietary tobramycin per batch of PMMA. Generic tobramycin eluted more than two times faster than proprietary tobramycin. The release mechanism started as dissolution-driven zero-order release for the generic bead set but for the proprietary bead set the released mechanism started as anomalous diffusion. The release mechanism progressed to diffusion-driven first-order release in both. The increased volume of the generic tobramycin caused more tobramycin to be available for release. The increased elution of tobramycin associated with the greater volume of generic tobramycin powder could lead to clinically higher levels of tobramycin in wound fluid and local tissues; however, the higher volume of powder could potentially cause greater mechanical compromise of the PMMA.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Bone Cements , Drugs, Generic/pharmacokinetics , Polymethyl Methacrylate , Tobramycin/pharmacokinetics , Anti-Bacterial Agents/chemistry , Chemistry, Pharmaceutical , Diffusion , Dosage Forms , Drugs, Generic/chemistry , Solubility , Spectrophotometry, Ultraviolet , Tobramycin/chemistry
12.
MMWR Morb Mortal Wkly Rep ; 55(49): 1327-9, 2006 Dec 15.
Article in English | MEDLINE | ID: mdl-17167395

ABSTRACT

Immunization registries are confidential, computerized information systems that collect and consolidate vaccination data from multiple health-care providers, generate reminder and recall notifications, and assess vaccination coverage within a defined geographic area. A registry with added capabilities, such as vaccine management, adverse event reporting, lifespan vaccination histories, and linkages with electronic data sources, is called an immunization information system (IIS). This report summarizes data from CDC's 2005 Immunization Information System Annual Report (IISAR), a survey of grantees in 50 states, five cities, and the District of Columbia (DC) that receive funding under section 317b of the Public Health Service Act. These data indicated that approximately 56% of U.S. children aged <6 years participated in an IIS, an increase from 48% in 2004. Moreover, 75% percent of public vaccination provider sites and 44% of private vaccination provider sites submitted vaccination data to an IIS during July-December 2005. These findings underscore the need to increase the number of participating children, from the current 13 million to approximately 21 million, to assure 95% participation of children aged <6 years and improve the effectiveness of U.S. immunization programs.


Subject(s)
Immunization Programs , Management Information Systems , Medical Records Systems, Computerized , Vaccination/standards , Child, Preschool , Humans , Infant , Infant, Newborn , United States
13.
MMWR Morb Mortal Wkly Rep ; 55(49): 1329-30, 2006 Dec 15.
Article in English | MEDLINE | ID: mdl-17167396

ABSTRACT

Beginning with the 2004-05 influenza season, the Advisory Committee on Immunization Practices (ACIP) recommended that all children aged 6-23 months receive influenza vaccinations annually. Other children recommended to receive influenza vaccinations include those aged 6 months-18 years who have certain high-risk medical conditions, those on chronic aspirin therapy, those who are household contacts of persons at high risk for influenza complications, and, since 2006, all children aged 24-59 months. Previously unvaccinated children aged <9 years need 2 doses administered at least 1 month apart to be considered fully vaccinated. This report assesses influenza vaccination coverage among children aged 6-23 months during the 2005-06 influenza season by using data from six immunization information system (IIS) sentinel sites. The findings demonstrate that vaccination coverage with 1 or more doses varied widely (range: 6.6% to 60.4%) among sites, with coverage increasing from the preceding influenza season in four of the six sites. However, <23% of children in five of the sites were fully vaccinated, underscoring the need for increased measures to improve the proportion of children who are fully vaccinated.


Subject(s)
Immunization Programs , Influenza Vaccines/administration & dosage , Management Information Systems , Medical Records Systems, Computerized , Vaccination/statistics & numerical data , Humans , Infant , Seasons , United States/epidemiology , Vaccination/standards
14.
Ying Yong Sheng Tai Xue Bao ; 15(3): 497-500, 2004 Mar.
Article in Chinese | MEDLINE | ID: mdl-15228005

ABSTRACT

Pot culture experiments were conducted to study the effect of industrial and sewage sludge on some enzyme activities and heavy metal concentrations in alluvial soil. The results showed that the heavy metals in both industrial and sewage sludge were mainly non-exchangeable, and those in sewage sludge had a lower concentration but a higher bio-availability than in industrial sludge. The application of sludge could increase the activities of soil urease, polyphenol oxidase and neutral phosphatase, and the polyphenol oxidase and neutral phosphatase activities showed a reverse relationship with the concentrations of soil exchangeable Zn and Cu. Soil polyphenol oxidase and catalase activities could be used to indicate the Zn pollution in soil.


Subject(s)
Metals, Heavy/analysis , Sewage , Soil/analysis , Catalase/metabolism , Catechol Oxidase/metabolism , Phosphoric Monoester Hydrolases/metabolism , Urease/metabolism
16.
J Environ Qual ; 30(6): 1940-9, 2001.
Article in English | MEDLINE | ID: mdl-11790000

ABSTRACT

Batch sequential extraction techniques for fractionating metals or metalloids in soils are time consuming and subject to several potential errors. The development of a continuous-flow sequential extraction method for soil As is described and assessed, having the benefits of simplicity, rapidity, less risk of contamination, and less vulnerability to changes in extraction conditions compared with traditional batch methods. The validated method was used to fractionate soil As using water, NaHCO3, NaOH, and HCl, followed by digestion of the residue with HNO3 and HF acids. The extracts and digests were analyzed for As by graphite furnace atomic absorption spectrometry. Good recoveries of total soil As (97-115%) were obtained and fractionation data generally comparable with those obtained using conventional batch techniques. Soils from a tin-mining area in Thailand and soils from As-contaminated cattle (Bos taurus) dip sites in Australia were used to test the applicability of the method, and to demonstrate the usefulness of the extractogram obtained. The ability to produce detailed extractograms for As and other elements (Al, Fe, and Ca) enabled an examination of elemental associations in individual fractions. With the exception of As extracted with HCl, the extractograms generally support previous suggestions of the likely forms or associations of As present in the different soil fractions.


Subject(s)
Arsenic/analysis , Environmental Monitoring/methods , Soil Pollutants/analysis , Animals , Arsenic/chemistry , Biological Availability , Cattle , Chemistry Techniques, Analytical/methods , Spectrophotometry, Atomic
17.
J Environ Qual ; 30(6): 1968-75, 2001.
Article in English | MEDLINE | ID: mdl-11790003

ABSTRACT

The enrichment or spiking of sewage sludge with heavy metals for experimental purposes is a fairly widely used, although sometimes controversial, technique. A study was undertaken, using a sequential fractionation scheme, to assess the degree of incorporation of Cu, Ni, and Zn into sewage sludge samples spiked with these metals and incubated for 6 mo. For all three metals, substantial proportions of the metals were incorporated into the sludge matrix, particularly as evidenced by their occurrence in the oxide-bound, organic-bound, and residual fractions. In particular, for Cu very little of the added copper remained in the sludge supernatant solution after 6 mo of incubation and, apart from at the highest level of Cu addition, there was very little difference in the fractional distribution of Cu between the Cu-spiked and non-Cu-spiked sludges. For Ni and Zn, however, although there was substantial incorporation of these metals into the sludge, the higher levels of Ni and Zn addition resulted in greater proportions of the metals in the most soluble fractions (soluble, exchangeable, specifically sorbed) compared with nonspiked sludges. The fractionation data for Ni also showed that large additions of Cu and Zn can affect the fractional distribution of Ni in the sludge. The drying of sewage sludge prior to analysis was shown to increase metal solubility in the sludge samples, and the potential implications of this finding for the prediction of sludge metal bioavailability are discussed.


Subject(s)
Copper/chemistry , Nickel/chemistry , Sewage/chemistry , Zinc/chemistry , Biological Availability , Copper/analysis , Environmental Monitoring , Nickel/analysis , Oxidation-Reduction , Solubility , Specimen Handling , Zinc/analysis
18.
Nat Genet ; 25(3): 279-83, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10888873

ABSTRACT

Multiple ovulations are uncommon in humans, cattle and many breeds of sheep. Pituitary gonadotrophins and as yet unidentified ovarian factors precisely regulate follicular development so that, normally, only one follicle is selected to ovulate. The Inverdale (FecXI) sheep, however, carries a naturally occurring X-linked mutation that causes increased ovulation rate and twin and triplet births in heterozygotes (FecXI/FecX+; ref. 1), but primary ovarian failure in homozygotes (FecXI/FecXI; ref. 2). Germ-cell development, formation of the follicle and the earliest stages of follicular growth are normal in FecXI/FecXI sheep, but follicular development beyond the primary stage is impaired. A second family unrelated to the Inverdale sheep also has the same X-linked phenotype (Hanna, FecXH). Crossing FecXI with FecXH animals produces FecXI/FecXH infertile females phenotypically indistinguishable from FecXI/FecXI females. We report here that the FecXI locus maps to an orthologous chromosomal region syntenic to human Xp11.2-11.4, which contains BMP15, encoding bone morphogenetic protein 15 (also known as growth differentiation factor 9B (GDF9B)). Whereas BMP15 is a member of the transforming growth factor beta (TGFbeta) superfamily and is specifically expressed in oocytes, its function is unknown. We show that independent germline point mutations exist in FecXI and FecXH carriers. These findings establish that BMP15 is essential for female fertility and that natural mutations in an ovary-derived factor can cause both increased ovulation rate and infertility phenotypes in a dosage-sensitive manner.


Subject(s)
Bone Morphogenetic Proteins/genetics , Growth Substances/genetics , Infertility, Female/genetics , Intercellular Signaling Peptides and Proteins , Mutation , Ovulation/physiology , X Chromosome , Amino Acid Sequence , Animals , Base Sequence , Bone Morphogenetic Protein 15 , Bone Morphogenetic Proteins/chemistry , Chromosome Mapping , DNA, Complementary , Female , Growth Differentiation Factor 9 , Growth Substances/chemistry , Humans , Male , Mice , Models, Molecular , Molecular Sequence Data , Oocytes/metabolism , Pedigree , Protein Conformation , Sheep
19.
Can J Anaesth ; 47(5): 463-6, 2000 May.
Article in English | MEDLINE | ID: mdl-10831205

ABSTRACT

PURPOSE: Intrathecal morphine administered prior to coronary artery revascularization (CABG) surgery was studied to determine its effects on the stress response. METHODS: In a single centre, open, randomized clinical trial, first time elective CABG surgery patients, < 75 yr, were studied. Control subjects (n=12) received a standardized anesthetic consisting of fentanyl (maximum cumulative dose of 35 microg x kg(-1)), propofol, and pancuronium. In addition, spinal subjects (n=13) received 1.0 mg (age > 60 yr) or 1.5 mg (age < or = 59 yr) intrathecal morphine prior to induction of anesthesia. Control subjects received continuous i.v. morphine at 2 mg x hr(-1) on arrival in the ICU with i.v. bolus morphine supplementation as required while spinal subjects received bolus i.v. morphine as required. Changes in plasma cortisol and catecholamine concentrations were measured preoperatively, poststernotomy, on admission to ICU, following tracheal extubation, at 0800 hr on the first postoperative day, and 24 and 48 hr after ICU admission. RESULTS: No differences between groups were detected for demographic variables. The percent change in cortisol concentration relative to preoperative values (control vs spinal; (38 (87) vs -41 (46)%: P < 0.05)) was lower in the spinal group on admission to ICU. The percent change in plasma epinephrine levels (control vs spinal) on admission to ICU (285 (337) vs -10 (37)%) and 0800 hr after surgery (314 (341) vs -4 (37)%) was also significantly different. CONCLUSION: Intrathecal morphine only partially attenuated the postsurgical stress response in CABG surgical patients.


Subject(s)
Analgesics, Opioid/pharmacology , Catecholamines/blood , Coronary Artery Bypass , Hydrocortisone/blood , Morphine/pharmacology , Adult , Aged , Analgesics, Opioid/administration & dosage , Female , Humans , Injections, Spinal , Male , Middle Aged , Morphine/administration & dosage
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