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The rate of bleeding complications following arterial switch operation is too low to independently justify a prospective randomised study for benefit from recombinant factor VIIa. We aimed to evaluate factor VIIa in a pilot study.
We performed a retrospective cohort study of patients undergoing arterial switch operation from 2012 to 2017. Nearest-neighbour propensity score matching on age, gender, weight, and associated cardiac defects was used to match 27 controls not receiving recombinant factor VIIa to 30 patients receiving recombinant factor VIIa. Fisher’s exact test was performed to compare categorical variables. Wilcoxon’s rank-sum test was used to compare continuous variables between cohorts.
Post-operative thrombotic complications were not associated with factor VIIa administration (Odds Ratio (OR) 0.28, 95% CI 0.005–3.77, p = 0.336), nor was factor VIIa administration associated with any re-explorations for bleeding. No intraoperative transfusion volumes were different between the recombinant factor VIIa cohort and controls. Post-operative prothrombin time (10.8 [10.3–12.3] versus 15.9 [15.1–17.2], p < 0.001) and international normalised ratio (0.8 [0.73–0.90] versus 1.3 [1.2–1.4], p < 0.001]) were lower in recombinant factor VIIa cohort relative to controls.
In spite of a higher post-bypass packed red blood cell transfusion requirement, patients receiving recombinant factor VIIa had a similar incidence of bleeding post-operatively. With no difference in thrombotic complications, and with improved post-operative laboratory haemostasis, a prospective randomised study is warranted to evaluate recombinant factor VIIa.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.
Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.
The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.
The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
The iconic Plaza Tree of Pueblo Bonito is widely believed to have been a majestic pine standing in the west courtyard of the monumental great house during the peak of the Chaco Phenomenon (AD 850–1140). The ponderosa pine (Pinus ponderosa) log was discovered in 1924, and since then, it has been included in “birth” and “life” narratives of Pueblo Bonito, although these ideas have not been rigorously tested. We evaluate three potential growth origins of the tree (JPB-99): Pueblo Bonito, Chaco Canyon, or a distant mountain range. Based on converging lines of evidence—documentary records, strontium isotopes (87Sr/86Sr), and tree-ring provenance testing—we present a new origin for the Plaza Tree. It did not grow in Pueblo Bonito or even nearby in Chaco Canyon. Rather, JPB-99 originated from the Chuska Mountains, over 50 km west of Chaco Canyon. The tree was likely carried to Pueblo Bonito sometime between AD 1100 and 1130, although why it was left in the west courtyard, what it meant, and how it might have been used remain mysteries. The origin of the Plaza Tree of Pueblo Bonito underscores deep cultural and material ties between the Chaco Canyon great houses and the Chuska landscape.
The recall of conditionally discharged forensic patients in England is a formal order from the Ministry of Justice under the Mental Health Act (1983) which has the power to revoke conditional release and direct readmission to hospital. Recall has significant implications for the individual and for hospital services, but despite this, little is known about predictors of recall for forensic patients.
We examined the rate of recall for 101 patients conditionally discharged from medium secure forensic inpatient services between 2007 and 2013. Demographic, clinical, and forensic factors were examined as possible predictors of time to recall using Cox regression survival techniques.
Conditionally discharged patients were followed for an average of 811 days, during which 45 (44.5%) were recalled to hospital. Younger age (HR 1.89; 95% CI 1.02–3.49; p = 0.04), non-white ethnicity (HR 3.44; 95% CI 1.45–8.13), substance abuse history (HR 2.52; 95% CI 1.17–5.43), early violence (HR 1.90; 95% CI 1.03–3.50), early childhood maladjustment (HR 1.92; 95% CI 1.01–3.68), treatment with a depot medication (HR 2.17; 95% CI 1.14–4.11), being known to mental health services (HR 3.44; 95% CI 1.06–11.16), and a psychiatric admission prior to the index admission (HR 2.44; 95% CI 1.08–5.52) were significantly associated with a shorter time to recall. Treatment with clozapine reduced the risk of recall to hospital (HR 0.40; 95% CI 0.20–0.79).
Time to recall can be predicted by a range of factors that are readily available to clinical teams. Further research is required to determine if targeted interventions can modify the likelihood or time to recall for conditionally released forensic patients.
Preferential dissolution of the biogenic carbonate polymorph aragonite promotes preservational bias in shelly marine faunas. While field studies have documented the impact of preferential aragonite dissolution on fossil molluscan diversity, its impact on regional and global biodiversity metrics is debated. Epicontinental seas are especially prone to conditions that both promote and inhibit preferential dissolution, which may result in spatially extensive zones with variable preservation. Here we present a multifaceted evaluation of aragonite dissolution within the Late Cretaceous Western Interior Seaway of North America. Occurrence data of mollusks from two time intervals (Cenomanian/Turonian boundary, early Campanian) are plotted on new high-resolution paleogeographies to assess aragonite preservation within the seaway. Fossil occurrences, diversity estimates, and sampling probabilities for calcitic and aragonitic fauna were compared in zones defined by depth and distance from the seaway margins. Apparent range sizes, which could be influenced by differential preservation potential of aragonite between separate localities, were also compared. Our results are consistent with exacerbated aragonite dissolution within specific depth zones for both time slices, with aragonitic bivalves additionally showing a statistically significant decrease in range size compared with calcitic fauna within carbonate-dominated Cenomanian–Turonian strata. However, we are unable to conclusively show that aragonite dissolution impacted diversity estimates. Therefore, while aragonite dissolution is likely to have affected the preservation of fauna in specific localities, time averaging and instantaneous preservation events preserve regional biodiversity. Our results suggest that the spatial expression of taphonomic biases should be an important consideration for paleontologists working on paleobiogeographic problems.
With more long-acting injectable (LAI) antipsychotics available for treating schizophrenia, each with variable durations of action (2 weeks to 3 months), it is important to have clear management strategies for patients developing breakthrough psychotic symptoms or experiencing symptomatic worsening on LAIs. However, no treatment guidelines or clinical practice pathways exist; health-care providers must rely on their own clinical judgment to manage these patients. This article provides practical recommendations—based on a framework of clinical, pharmacokinetic, and dosing considerations—to guide clinicians’ decisions regarding management of breakthrough psychotic symptoms. Management options include ruling out/addressing medical illness or substance abuse/misuse as a contributing factor, addressing stressors, optimizing nonpharmacologic treatments, treating medical/psychiatric comorbidities, ensuring proper LAI administration technique, addressing missed LAI doses or lack of steady-state attainment, and increasing LAI dose directly or indirectly by shortening the injection interval (off-label). If these strategies do not work sufficiently with frequent monitoring, the LAI could be supplemented with a low dose of the corresponding oral formulation for fast symptom control (off-label). However, caution should be exercised with this strategy, because data on the safety of concomitant use of LAI and oral antipsychotics (OAPs) are limited, especially over extended periods. If symptoms abate, therapy optimization could be continued and slow discontinuation of the OAP could be considered. For persistent/worsening symptoms, the OAP should be increased to optimum effective dose while intensifying the initial steps used before it was added. If this fails, switching the OAP or LAI could be considered. We believe that these strategies will help clinicians manage breakthrough psychotic symptoms during LAI treatment and improve overall outcomes among those who can benefit from LAIs.
We present first imaging results from the PALM-3000 adaptive optics system and PHARO camera on the Hale 5 m telescope. Observations using a vector vortex coronagraph have given us direct detections of the two-ring dusty debris system around the star HD 141569. Our observations reveal the inner clearing in the disk to unprecedentedly small angular separations, and are the most sensitive yet at the H and K bands. We are for the first time able to measure and compare the colors of the scattered light in the inner and outer dust rings, and find that the outer ring is significantly bluer than the inner ring.
Ground sections were prepared of the seven root apices of five teeth preserved in the fossil hemi-mandible specimen, KNM-ER 1817, from Koobi Fora, Kenya. The sections were studied with transmitted polarised light microscopy. Despite the poor gross macroscopic preservation of the mandibular bone, the dentine microstructure was well preserved. Good details of typical dentine structure were observed in many of the sections including both short-period daily incremental lines and long-period lines. The spacing between consecutive daily incremental lines were compared with those published for dentine in modern humans and other primates. Close to the root surface, there appears to be a consistent rate of ~2.5 µm (micrometres) per day. Coarser accentuated lines (Owen’s lines) together with long-period lines were also clearly visible in the largest apical root section of the M3. These were used to reconstruct the slowing rates of root extension in the last 4 mm of the mesial M3 apex of KNM-ER 1817, which were then compared with those known for a sample of modern human molars.
Auxinic herbicides are widely used for control of broadleaf weeds in cereal
crops and turfgrass. These herbicides are structurally similar to the
natural plant hormone auxin, and induce several of the same physiological
and biochemical responses at low concentrations. After several decades of
research to understand the auxin signal transduction pathway, the receptors
for auxin binding and resultant biochemical and physiological responses have
recently been discovered in plants. However, the precise mode of action for
the auxinic herbicides is not completely understood despite their extensive
use in agriculture for over six decades. Auxinic herbicide-resistant weed
biotypes offer excellent model species for uncovering the mode of action as
well as resistance to these compounds. Compared with other herbicide
families, the incidence of resistance to auxinic herbicides is relatively
low, with only 29 auxinic herbicide-resistant weed species discovered to
date. The relatively low incidence of resistance to auxinic herbicides has
been attributed to the presence of rare alleles imparting resistance in
natural weed populations, the potential for fitness penalties due to
mutations conferring resistance in weeds, and the complex mode of action of
auxinic herbicides in sensitive dicot plants. This review discusses recent
advances in the auxin signal transduction pathway and its relation to
auxinic herbicide mode of action. Furthermore, comprehensive information
about the genetics and inheritance of auxinic herbicide resistance and case
studies examining mechanisms of resistance in auxinic herbicide-resistant
broadleaf weed biotypes are provided. Within the context of recent findings
pertaining to auxin biology and mechanisms of resistance to auxinic
herbicides, agronomic implications of the evolution of resistance to these
herbicides are discussed in light of new auxinic herbicide-resistant crops
that will be commercialized in the near future.
To assess whether a print-based intervention led to increased contact with consumer health organisations (CHOs) by general practice patients with chronic disease.
CHOs can enhance people's capacity to manage chronic illness by providing information, education and psychosocial support. However, these organisations appear to be grossly under-utilised by patients and clinicians.
A total of 276 patients completed a computer-assisted telephone interview before randomisation to an intervention (n = 141) or control (n = 135) group. The intervention consisted of mailed printed materials designed to encourage contact with a CHO relevant to the patient's main diagnosed chronic condition. Follow-up interviews were conducted 4 and 12 months later.
Patients with conditions other than diabetes who received the intervention were twice as likely as those in the control group to contact a consumer health organisation during the 12-month study period: 41% versus 21% (P < 0.001). No such effect was found for diabetes patients, probably because of pre-existing high levels of contact with diabetes organisations. The intervention package received strong patient endorsement. Low-intensity interventions may be effective in improving access to CHOs for patients with chronic disease.
Weed science has contributed much to agriculture, forestry and natural resource management during its history. However, if it is to remain relevant as a scientific discipline, it is long past time for weed scientists to move beyond a dominating focus on herbicide efficacy testing and address the basic science underlying complex issues in vegetation management at many levels of biological organization currently being solved by others, such as invasion ecologists and molecular biologists. Weed science must not be circumscribed by a narrowly-defined set of tools but rather be seen as an integrating discipline. As a means of assessing current and future research interests and funding trends among weed scientists, the Weed Science Society of America conducted an online survey of its members in summer of 2007. There were 304 respondents out of a membership of 1330 at the time of the survey, a response rate of 23%. The largest group of respondents (41%) reported working on research problems primarily focused on herbicide efficacy and maintenance, funded mainly by private industry sources. Another smaller group of respondents (22%) reported focusing on research topics with a complex systems focus (such as invasion biology, ecosystem restoration, ecological weed management, and the genetics, molecular biology, and physiology of weedy traits), funded primarily by public sources. Increased cooperation between these complementary groups of scientists will be an essential step in making weed science increasingly relevant to the complex vegetation management issues of the 21st century.
Congenital heart defects are the most common cause of death in infants and young children in the developed world. As the mortality in this population has declined to less than 5%, more attention is being focused now on reducing post-procedural morbidities that may seriously impact the patient and their families. Because of multiple reasons, paediatric cardiac surgery and anaesthesia is a perfect model for studying human errors and their impact on patient safety. Congenital cardiac disease is a common lesion causing much morbidity, pain, and loss of life. Over 44,000 surgical procedures are performed yearly to repair congenital cardiac problems in the United States alone. The reduction or elimination of iatrogenic adverse outcomes, given the current mortality rates of 4.2%–4.5%, might lead to as many as 500 children achieving better outcomes or shorter hospitalizations.
Efforts to quantify the frequency of complications related to anaesthesia in patients undergoing congenital cardiac surgery have been difficult to date because of the low occurrence of this surgery compared to other surgeries on children and the relatively rare incidence of complications related to anaesthesia in this population. Anaesthesiologists play a crucial role in the reduction, recognition, and timely treatment of medical errors that impact this morbidity. Paediatric cardiac surgery encompasses many complex procedures that are highly dependent upon a sophisticated organizational structure, effective communication, coordinated efforts of multiple individuals working as a team, and high levels of cognitive and technical performance. Human factor error analysis in this patient population has shown how frequently both minor and major errors occur. The goal of this paper is to outline the frequency and sources of these errors and to suggest treatment strategies which may minimize their occurrence.
Louise T. Humphrey, Palaeontology Department, Natural History Museum Cromwell Road, London SW7 5BD, UK,
Teresa E. Jeffries, Department of Mineralogy, The Natural History Museum Cromwell Road, London SW7 5BD, UK,
M. Christopher Dean, Evolutionary Anatomy Unit, Department of Anatomy and Developmental Biology University College London, London WC1E 6BT, UK
Enamel is the hard crystalline external covering of teeth, and has a mineral component that closely resembles hydroxyapatite (Boyde, 1989; Brudevold and Soremark, 1967). The chemical constituents of hydroxyapatite are tolerant to substitution by a range of trace elements, and are readily incorporated into enamel formation at the time of environmental exposure. The composition of sub-surface enamel is fixed before tooth emergence, and is therefore able to provide a retrospective and relatively permanent record of the trace elements absorbed during the period of enamel formation. The information locked within this deep enamel can provide evidence of early nutrition, residential mobility, and exposure to toxic metals. The incorporation of some trace elements into enamel hydroxyapatite also has the potential to affect susceptibility to caries. The trace element composition of enamel has a broad relevance in disciplines ranging from dentistry and child health (Brown et al., 2004; Dolphin et al., 2005) to forensics (Gulson et al., 1997a) and archaeology (Budd et al., 2000). Two trace elements of particular interest are lead (Pb) and zinc (Zn).
Lead toxicity remains a major public health concern, particularly in relation to its neurological effects on infants and young children (Bellinger et al., 1984; Goyer, 1996). Lead enters the body from contaminated food and drinking water, and inhaled air and dust, and accumulates gradually in calcified tissues. Non-food sources include lead emissions from gasoline, smelter emissions, lead-based paints and glazed food containers (Jarup, 2003).