To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A new and an essential reference work for any international human rights law academic, student or practitioner, A Commentary on the International Covenant on Civil and Political Rights spans all substantive rights of the International Covenant on Civil and Political Rights (ICCPR), as approached from the perspective of the ICCPR as an integrated, coherent scheme of rights protection. In detailed coverage of the Human Rights Committee's output when monitoring ICCPR compliance, Paul M. Taylor offers extraordinary access to forty years of its concluding observations, views and general comments organised thematically. This Commentary is a solid and practical introduction to any and all of the civil and political rights in the ICCPR, and a rare resource explaining the requirements for domestic implementation of ICCPR standards. An indispensable research tool for any serious enquirer into the subject, the Commentary speaks to the accomplishments of the ICCPR in striving for universal human rights standards.
Changing rates of water input can affect both the flow of glaciers and ice sheets and their propensity to crevasse. Here we examine geodetic and seismic observations during two substantial (10–18-times background velocity) rain-induced glacier accelerations at Haupapa/Tasman Glacier, New Zealand. Changes in rain rate result in glacier acceleration and associated uplift, which propagate down-glacier. This pattern of acceleration results in a change to the strain rate field, which correlates with an order of magnitude increase in the apparent seismicity rate and an overall down-glacier migration in located seismicity. After each acceleration event the apparent seismicity rate decreases to below the pre-acceleration rate for 3 days. This suggests that seismic events associated with surface crevasse growth occur early during phases of glacier acceleration due to elevated extensional stresses, and then do not occur again until stresses recover.
To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
The Glen Rose and Walnut formations of southcentral and northcentral Texas comprise shallow-water carbonates deposited during the late Aptian to middle Albian on a carbonate platform. The formations are famous for their rich fossil faunas. Although bryozoans are absent in late Aptian sediments, they are frequently found encrusting bivalve shells from the early to middle Albian parts of these formations. Here, we describe the cyclostome bryozoan fauna, which includes six species; Stomatopora sp., Oncousoecia khirar n. sp., Reptomultisparsa mclemoreae n. sp., Hyporosopora keera n. sp., Mesonopora bernardwalteri n. sp., and ?Unicavea sp. Most cyclostomes are found encrusting rudist shells from Unit 2 of the Lower Member of the Glen Rose Formation and units 3 and 6 of the Upper Member of the Glen Rose Formation.
Gymnolaemate bryozoans are common encrusters on bivalve shells from the early to middle Albian parts of the Glen Rose and Walnut formations of southcentral and northcentral Texas. Here, we report for the first time the presence of seven gymnolaemate bryozoans, all of which represent new species. They include the bioimmured ctenostome Simplicidium jontoddi n. sp., and the cheilostomes Rhammatopora glenrosa n. sp., Iyarispora ikaanakiteeh n. gen. n. sp., Iyarispora chiass n. gen. n. sp., Charixa bispinata n. sp., Charixa sexspinata n. sp., and Charixa emanuelae n. sp. The Glen Rose bryozoans slightly antedate the commencement of an explosive bryozoan radiation and the first appearance of neocheilostomes in the late Albian. Although the diversity of cheilostomes in the Glen Rose and Walnut formations is similar to that of cyclostomes, cheilostomes are more abundant and produced larger colonies. These formations therefore yield the oldest known bryozoan assemblage dominated in terms of biomass by cheilostomes. The genus concept of Charixa is discussed and amended.
We have searched optical u′g′r′i′z′ imaging of 22 deg2 centred on the nearby giant elliptical galaxy NGC 5128 for new dwarf galaxies in the Centaurus A group. We report 45 promising new candidates, which are broadly consistent with the properties of nearby dwarf spheroidal galaxies and extend the size-luminosity relation toward fainter total luminosities and smaller sizes for known dwarf galaxies outside the Local Group (LG). Altogether, these new results show NGC 5128 to be the host of a large reservoir of low-mass dwarf galaxies that is at least as rich as that of the LG and is ripe for detailed follow-up observations.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
Chemoinformatics (or as it is also known, cheminformatics) basically relates to the storage and manipulation of chemical data. Many of the techniques gathered together under this title pre-date its introduction, and perhaps the term was coined to explicitly signal that a similar discipline to bioinformatics exists within the realm of theoretical chemistry. The term is also heavily related to drug discovery, given that those with the largest commercial interest in systematic computational analysis of molecules are drug companies. This area is explicitly addressed elsewhere in this book (see Chapter 24) and so here we restrict ourselves to the computational representation of molecules, the derivation of useful molecular properties, application of the techniques to biological systems, and the storage and comparison of those data.
Chemoinformatics can be used on chemicals of any elemental composition, however it is most well developed for small organic molecules, i.e. those compounds that are mostly made from combinations of carbon, hydrogen, nitrogen, oxygen and sulfur, with the addition of small amounts of other elements, most notably the halogens (fluorine, chlorine, bromium, iodine) and, particularly for biological chemistry, phosphorous. While small positively charged metal ions are commonly encountered in compounds (often as counter ions to organic acids) larger metal ions are comparably rare.
Chemoinformatics calculations can address features of single molecules; however, they become invaluable when dealing with a set of molecules among which certain features need to be compared. Like most computational processes, it is of course possible to perform many of the calculations described here by hand, albeit many of these are tedious and repetitive in nature. Once automated, chemoinformatics allows the comparison of molecules to/within large datasets, and many calculations specifically involve comparison of one molecule to another. The concept of similarity is central to chemoinformatics studies, as often molecules classed as similar can be expected to exhibit similar physiological behaviours, and particularly bind to macromolecules in a similar way. This can often be done by direct comparison of the molecular structures (if they differ only by a single atom or bond); however, the ideal is to find molecules that possess similar properties, but come from distinct chemical families.
Finally, it should always be borne in mind that chemoinformatics is a branch of theoretical chemistry. A great many of the techniques used in this context rely on approximations to the exact physics occurring in the molecule.
Dyspnea is a common presenting problem that creates a diagnostic challenge for physicians in the emergency department (ED). While the differential diagnosis is broad, acute decompensated heart failure (ADHF) is a frequent cause that can be challenging to differentiate from other etiologies. Recent studies have suggested a potential diagnostic role for emergency lung ultrasound (US). The objective of this systematic review was to assess the accuracy of early bedside lung US in patients presenting to the ED with dyspnea.
A systematic search of EMBASE, PubMed, and the Cochrane Library was performed in addition to a grey literature search. We selected prospective studies that reported on the sensitivity and specificity of B-lines from early lung ultrasound in dyspneic patients presenting to the ED. Selected studies underwent quality assessment using the Critical Appraisal and Skills Program (CASP) questionnaire.
Data Extraction and Synthesis
The search yielded 3674 articles; seven studies met inclusion criteria and fulfilled CASP requirements for a total of 1861 patients. Summary statistics from the meta-analysis showed that as a diagnostic test for ADHF, bedside lung US had a pooled sensitivity of 82.5% (95% confidence interval [CI]=66.4% to 91.8%) and a pooled specificity of 83.6% (95% CI=72.4% to 90.8%).
Our results suggest that in patients presenting to the ED with undifferentiated dyspnea, B-lines from early bedside lung US may be reliably used as an adjunct to current diagnostic methods. The incorporation of lung US may lead to more appropriate and timely diagnosis of patients with undifferentiated ADHF.
To assess general medical residents’ familiarity with antibiograms using a self-administered survey
Cross-sectional, single-center survey
Residents in internal medicine, family medicine, and pediatrics at an academic medical center
Participants were administered an anonymous survey at our institution during regularly scheduled educational conferences between January and May 2012. Questions collected data regarding demographics, professional training; further open-ended questions assessed knowledge and use of antibiograms regarding possible pathogens, antibiotic regimens, and prescribing resources for 2 clinical vignettes; a series of directed, closed-ended questions followed. Bivariate analyses to compare responses between residency programs were performed.
Of 122 surveys distributed, 106 residents (87%) responded; internal medicine residents accounted for 69% of responses. More than 20% of residents could not accurately identify pathogens to target with empiric therapy or select therapy with an appropriate spectrum of activity in response to the clinical vignettes; correct identification of potential pathogens was not associated with selecting appropriate therapy. Only 12% of respondents identified antibiograms as a resource when prescribing empiric antibiotic therapy for scenarios in the vignettes, with most selecting the UpToDate online clinical decision support resource or The Sanford Guide. When directly questioned, 89% reported awareness of institutional antibiograms, but only 70% felt comfortable using them and only 44% knew how to access them.
When selecting empiric antibiotics, many residents are not comfortable using antibiograms as part of treatment decisions. Efforts to improve antibiotic use may benefit from residents being given additional education on both infectious diseases pharmacotherapy and antibiogram utilization.
Structured clinical judgement tools provide scope for the standardisation of forensic service gatekeeping and also allow identification of heuristics in this decision process. The DUNDRUM-1 triage tool was completed retrospectively for 121 first-time referrals to forensic services in South Wales. Fifty were admitted to medium security, 49 to low security and 22 remained in open conditions.
DUNDRUM-1 total scores differed appropriately between different levels of security. However, regression revealed heuristic anchoring on the ‘legal process’ and ‘immediacy of risk due to mental disorder’ items.
Patient placement was broadly aligned with DUNDRUM-1 recommendations. However, not all triage items informed gatekeeping decisions. It remains to be seen whether decisions anchored in this way are effective.
Declaration of interest
Dr Mark Freestone gave permission for AUC values from Freestone et al. (2015) to be presented here for comparison.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.
Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.
The Vertical Agreements Regulation may be judged in one of two ways, each yielding a different conclusion. It may be regarded, on the one hand, merely as a limited measure required at a particular time in the development of competition policy to correct some of the more obvious errors of previous Regulations. On the other hand, it may be assessed for its potential as a template for future Regulations. Is it to be regarded as a means of rectifying historic block exemptions or is it at the cutting edge of progressive policy? Without doubt it appears chronologically at one of the most important shifts in competition policy in decades and that is why there is much to be gained from reviewing the Regulation critically for improvements that can be carried forward into future Regulations.
This work builds on a survey first done in 1999 to understand how old age psychiatry teaching is embedded in undergraduate medical schools in the UK and Ireland and the influence of academic old age psychiatrists on teaching processes. We invited deans of 31 medical schools in the UK and Ireland in 2015 to complete an online survey to reassess the situation 16 years later.
Response rate was 74%. As found in the original survey, there was variation across medical schools in how old age psychiatry is taught. Half of schools stated there was not enough space in the curriculum dedicated to old age psychiatry, and not all medical school curricula offered a clinical attachment. Medical schools that involved academic old age psychiatrists in teaching (59%) showed a greater diversity of teaching methods.
There is a need to recognise the importance of old age psychiatry teaching, with the consensus of opinion continuing to be that more curriculum space needs to be given to old age psychiatry. To achieve this we advocate increasing the number of old age psychiatrists with teaching roles, as relying on academics to teach and lead on curriculum development is challenging given their greater research pressures.
One common assumption in interpreting ice-core CO2 records is that diffusion in the ice does not affect the concentration profile. However, this assumption remains untested because the extremely small CO2 diffusion coefficient in ice has not been accurately determined in the laboratory. In this study we take advantage of high levels of CO2 associated with refrozen layers in an ice core from Siple Dome, Antarctica, to study CO2 diffusion rates. We use noble gases (Xe/Ar and Kr/Ar), electrical conductivity and Ca2+ ion concentrations to show that substantial CO2 diffusion may occur in ice on timescales of thousands of years. We estimate the permeation coefficient for CO2 in ice is ∼4 × 10−21 mol m−1 s−1 Pa−1 at −23°C in the top 287 m (corresponding to 2.74 kyr). Smoothing of the CO2 record by diffusion at this depth/age is one or two orders of magnitude smaller than the smoothing in the firn. However, simulations for depths of ∼930–950 m (∼60–70 kyr) indicate that smoothing of the CO2 record by diffusion in deep ice is comparable to smoothing in the firn. Other types of diffusion (e.g. via liquid in ice grain boundaries or veins) may also be important but their influence has not been quantified.
The Holocene portion of the Siple Dome (Antarctica) ice core was dated by interpreting the electrical, visual and chemical properties of the core. The data were interpreted manually and with a computer algorithm. The algorithm interpretation was adjusted to be consistent with atmospheric methane stratigraphic ties to the GISP2 (Greenland Ice Sheet Project 2) ice core, 10Be stratigraphic ties to the dendrochronology 14 C record and the dated volcanic stratigraphy. The algorithm interpretation is more consistent and better quantified than the tedious and subjective manual interpretation.
Using TAURUS – an Imaging Fabry Perot system in conjunction with the IPCS on the AAT, we have studied the velocity field of the Ha emission line at a spatial resolution of 1.7″ over the dark lane structure of Centaurus A. The derived velocity field is quite symmetrical and strongly suggests that the emission line material is orbiting the elliptical component, as a warped disc.