End-of-life care pathways for improving outcomes in caring for the dying (Review)

Background This is an updated version of a Cochrane review first published in Issue 1, 2010 of The Cochrane Library. In many clinical areas, integrated care pathways are utilised as structured multidisciplinary care plans that detail essential steps in caring for patients with specific clinical problems. In particular, care pathways for the dying have been developed as a model to improve care of patients who are in the last days of life. The care pathways were designed with an aim of ensuring that the most appropriate management occurs at the most appropriate time and that it is provided by the most appropriate health professional. There have been sustained concerns about the safety of implementing end-of-life care pathways, particularly in the UK. Therefore, there is a significant need for clinicians and policy makers to be informed about the effects of end-of-life care pathways with a systematic review. Objectives To assess the effects of end-of-life care pathways, compared with usual care (no pathway) or with care guided by another end-of-life care pathway across all healthcare settings (e.g. hospitals, residential aged care facilities, community). In particular, we aimed to assess the effects on symptom severity and quality of life of people who are dying; those related to the care such as families, carers and health professionals; or a combination of these. Search Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2013), MEDLINE, EMBASE, PsycINFO, CINAHL, review articles and reference lists of relevant articles.We conducted the original search in September 2009, and the updated search in June 2013. Selection Criteria All randomised controlled trials (RCTs), quasi-randomised trial or high-quality controlled before-and-after studies comparing use versus non-use of an end-of-life care pathway in caring for the dying. Data Collection and Analysis Two review authors assessed the results of the searches against the predetermined criteria for inclusion. Main Results The original review identified 920 titles. The updated search found 2042 potentially relevant titles (including the original 920), but no additional studies met criteria for inclusion in the review update. Authors’ Conclusions With sustained concerns about the safety of the pathway implementation and the lack of available evidence on important patient and relative outcomes, recommendations for the use of end-of-life pathways in caring for the dying cannot be made. Since the last version of this review, no new studies met criteria for inclusion in the review update. With recently documented concerns related to the potential adverse effects associated with Liverpool Care Pathway (the most commonly used end-of-life care pathway), we do not recommend decision making based on indirect or low-quality evidence. All health services using end-of-life care pathways are encouraged to have their use of the pathway, to date, independently audited. Any subsequent use should be based on carefully documented evaluations. Large RCTs or other well-designed controlled studies are urgently required for the evaluation of the use of end-of-life care pathways in caring for dying people in various clinical settings. In future studies, outcome measures should include benefits or harms concerning the outcomes of interest in this review in relation to patients, families, carers and health professionals.

Vibrational spectroscopy of the borate mineral chambersite MnB7O13Cl – Implications for the molecular structure

Chambersite is a manganese borate mineral with formula: MnB7O13Cl and occurs as colorless crystals in the monoclinic pyramidal crystal system. Raman bands at 902, 920, 942 and 963 cm-1 are assigned to the BO stretching vibration of the B7O13 units. Raman bands at 1027, 1045, 1056, 1075 and 1091 cm-1 are attributed to the BCl in-plane bending modes. The intense infrared band at 866 cm-1 is assigned to the trigonal borate stretching modes. The Raman band at 660 cm-1 together with bands at 597, 642 679, 705 and 721 cm-1 are assigned to the trigonal and tetrahedral borate bending modes. The molecular structure of a natural chambersite has been assessed using vibrational spectroscopy.

Rice ragged stunt oryzavirus genome segment S4 could encode an RNA dependent RNA polymerase and a second protein of unknown function

The complete nucleotide sequence of genome segment S4 of rice ragged stunt oryzavirus (RRSV, Thai-isolate) was determined. The 3823 bp sequence contains two large open reading frames (ORFs). ORF1, spanning nucleotides 12 to 3776, is capable of encoding a protein of M(r) 141,380 (P4a). The P4a amino acid sequence predicted from the nucleotide sequence contains sequence motifs conserved in RNA-dependent RNA polymerases (RDRPs). When compared for evolutionary relationships with RDRPs of other reoviruses using the amino acid sequences around the conserved GDD motif, P4a was shown to be more related to Nilaparvata lugens reovirus and reovirus serotype 3 than to rice dwarf phytoreovirus, bovine rotavirus or bluetongue virus. The ORF2, spanning nucleotides 491 to 1468, is out of frame with ORF1 and is capable of encoding a protein of 36, 920 (P4b). Coupled in vitro transcription-translation from cloned ORF2 in wheat germ extract confirmed the existence of ORF2 but in vivo production and possible function of P4b is yet to be determined.

Regulation and integral control of an underactuated robotic system using IDA-PBC with dynamic extension

This paper proposes a method for design of a set-point regulation controller with integral action for an underactuated robotic system. The robot is described as a port-Hamiltonian system, and the control design is based on a coordinate transformation and a dynamic extension. Both the change of coordinates and the dynamic extension add extra degrees of freedom that facilitate the solution of the matching equation associated with interconnection and damping assignment passivity-based control designs (IDA-PBC). The stability of the controlled system is proved using the closed loop Hamiltonian as a Lyapunov candidate function. The performance of the proposed controller is shown in simulation.

“Best interests” and withholding and withdrawing life-sustaining treatment from an adult who lacks capacity in the parens patriae jurisdiction

Disputes about withholding and withdrawing life-sustaining treatment are increasingly coming before Australian Supreme Courts. Such cases are generally heard in the parens patriae jurisdiction where the test applied is what is in the patient’s “best interests”. However, the application of the “best interests” test, and its meaning, remains unclear in this context. To shed light on this emerging body of jurisprudence, this article analyses the Australian superior court decisions that consider an adult’s best interests in the context of decisions about life-sustaining treatment. We identify a number of themes from the current body of cases and consider how these themes may guide future decision-making. After then considering the law in the United Kingdom, we suggest an approach for assessing best interests that could be adopted by Australian Supreme Courts. We argue that the suggested approach will lead to a more structured and systematic decision-making process that better promotes the best interests of the patient.

Temporal Characterization of Ossification of the Crania in Australian Subadults: New standards for Age Estimation using Computed Tomography

After attending this presentation, attendees will gain awareness of the ontogeny of cranial maturation, specifically: (1) the fusion timings of primary ossification centers in the basicranium; and (2) the temporal pattern of closure of the anterior fontanelle, to develop new population-specific age standards for medicolegal death investigation of Australian subadults. This presentation will impact the forensic science community by demonstrating the potential of a contemporary forensic subadult Computed Tomography (CT) database of cranial scans and population data, to recalibrate existing standards for age estimation and quantify growth and development of Australian children. This research welcomes a study design applicable to all countries faced with paucity in skeletal repositories. Accurate assessment of age-at-death of skeletal remains represents a key element in forensic anthropology methodology. In Australian casework, age standards derived from American reference samples are applied in light of scarcity in documented Australian skeletal collections. Currently practitioners rely on antiquated standards, such as the Scheuer and Black1 compilation for age estimation, despite implications of secular trends and population variation. Skeletal maturation standards are population specific and should not be extrapolated from one population to another, while secular changes in skeletal dimensions and accelerated maturation underscore the importance of establishing modern standards to estimate age in modern subadults. Despite CT imaging becoming the gold standard for skeletal analysis in Australia, practitioners caution the application of forensic age standards derived from macroscopic inspection to a CT medium, suggesting a need for revised methodologies. Multi-slice CT scans of subadult crania and cervical vertebrae 1 and 2 were acquired from 350 Australian individuals (males: n=193, females: n=157) aged birth to 12 years. The CT database, projected at 920 individuals upon completion (January 2014), comprises thin-slice DICOM data (resolution: 0.5/0.3mm) of patients scanned since 2010 at major Brisbane Childrens Hospitals. DICOM datasets were subject to manual segmentation, followed by the construction of multi-planar and volume rendering cranial models, for subsequent scoring. The union of primary ossification centers of the occipital bone were scored as open, partially closed or completely closed; while the fontanelles, and vertebrae were scored in accordance with two stages. Transition analysis was applied to elucidate age at transition between union states for each center, and robust age parameters established using Bayesian statistics. In comparison to reported literature, closure of the fontanelles and contiguous sutures in Australian infants occur earlier than reported, with the anterior fontanelle transitioning from open to closed at 16.7±1.1 months. The metopic suture is closed prior to 10 weeks post-partum and completely obliterated by 6 months of age, independent of sex. Utilizing reverse engineering capabilities, an alternate method for infant age estimation based on quantification of fontanelle area and non-linear regression with variance component modeling will be presented. Closure models indicate that the greatest rate of change in anterior fontanelle area occurs prior to 5 months of age. This study complements the work of Scheuer and Black1, providing more specific age intervals for union and temporal maturity of each primary ossification center of the occipital bone. For example, dominant fusion of the sutura intra-occipitalis posterior occurs before 9 months of age, followed by persistence of a hyaline cartilage tongue posterior to the foramen magnum until 2.5 years; with obliteration at 2.9±0.1 years. Recalibrated age parameters for the atlas and axis are presented, with the anterior arch of the atlas appearing at 2.9 months in females and 6.3 months in males; while dentoneural, dentocentral and neurocentral junctions of the axis transitioned from non-union to union at 2.1±0.1 years in females and 3.7±0.1 years in males. These results are an exemplar of significant sexual dimorphism in maturation (p<0.05), with girls exhibiting union earlier than boys, justifying the need for segregated sex standards for age estimation. Studies such as this are imperative for providing updated standards for Australian forensic and pediatric practice and provide an insight into skeletal development of this population. During this presentation, the utility of novel regression models for age estimation of infants will be discussed, with emphasis on three-dimensional modeling capabilities of complex structures such as fontanelles, for the development of new age estimation methods.

Tendinopathy alters cumulative transverse strain in the patellar tendon postexercise.

Introduction This research evaluated the effect of tendinopathy on the cumulative transverse strain response of the patellar tendon to a bout of resistive quadriceps exercise. Methods Nine adults with unilateral patellar tendinopathy (age 18.2±0.7 years, height 1.92±0.06 m and weight 76.8±6.8 kg) and ten healthy adults free of knee pain (age 17.8±0.8 years, height 1.83±0.05 m and weight 73.2±7.6 kg) underwent standardised sagittal sonograms (7.2–14 MHz linear–array transducer) of both patellar tendons immediately prior and following 45 repetitions of a double–leg decline–squat exercise performed against a resistance of 145% bodyweight. Tendon thickness was determined 5–mm and 25–mm distal to the patellar pole. Transverse Hencky strain was calculated as the natural log of the ratio of post– to pre–exercise tendon thickness and expressed as a percentage. Measures of tendon echogenicity were calculated within the superficial and deep aspects of each tendon site from gray–scale profiles. Intratendinous microvessels were evaluated using power Doppler ultrasound. Results The cumulative transverse strain response to exercise in symptomatic tendinopathy was significantly lower than that of asymptomatic and healthy tendon (P<.05). There was also a significant reduction (57%) in the area of microvascularity immediately following exercise (P=.05), which was positively correlated (r=0.93, P<.05) with VISA-P score. Conclusions This study is the first to show that patellar tendinopathy is associated with an altered morphological and mechanical response of the tendon to exercise, which is manifest by a reduction in cumulative transverse strain and microvascularity, when present. Research directed toward identifying factors that influence the acute microvascular and transverse strain response of the patellar tendon to exercise in the various stages of tendinopathy is warranted.

Confirmatory factor analysis and invariance testing of the Young Carer of Parents Inventory (YCOPI)

Objective Research into youth caregiving in families where a parent experiences a significant medical condition has been hampered by a lack of contextually sensitive measures of the nature and breadth of young caregiving experiences. This study examined the factor structure and measurement invariance of such a measure called the Young Carer of Parents Inventory (YCOPI; Pakenham et al., 2006) using confirmatory factor analysis across 3 groups of youth. The YCOPI has 2 parts: YCOPI-A with 5 factors assessing caregiving experiences that are applicable to all caregiving contexts; YCOPI-B with 4 factors that tap dimensions related to youth caregiving in the context of parent illness. Design Two samples (ages 9–20 years) were recruited: a community sample of 2,429 youth from which 2 groups were derived (“healthy” family [HF], n = 1760; parental illness [PI], n = 446), and a sample of 130 youth of a parent with multiple sclerosis). Results With some modification, the YCOPI-A demonstrated a replicable factor structure across 3 groups, and exhibited only partial measurement invariance across the HF and PI groups. The impact of assuming full measurement invariance on latent mean differences appeared small, supporting use of the measure in research and applied settings when estimated using latent factors and controlling for measurement invariance. PI youth reported significantly higher scores than did HF youth on all YCOPI-A subscales. The YCOPI-B requires some modifications, and further development work is recommended. Conclusion The factor structure that emerged and the addition of new items constitutes the YCOPI-Revised. Findings support the use of the YCOPI-Revised in research and applied settings.

Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach : a longitudinal study

Background The high recurrence rate of chronic venous leg ulcers has a significant impact on an individual’s quality of life and healthcare costs. Objectives This study aimed to identify risk and protective factors for recurrence of venous leg ulcers using a theoretical approach by applying a framework of self and family management of chronic conditions to underpin the study. Design Secondary analysis of combined data collected from three previous prospective longitudinal studies. Setting The contributing studies’ participants were recruited from two metropolitan hospital outpatient wound clinics and three community-based wound clinics. Participants Data were available on a sample of 250 adults, with a leg ulcer of primarily venous aetiology, who were followed after ulcer healing for a median follow-up time of 17 months after healing (range: 3 to 36 months). Methods Data from the three studies were combined. The original participant data were collected through medical records and self-reported questionnaires upon healing and every 3 months thereafter. A Cox proportion-hazards regression analysis was undertaken to determine the influential factors on leg ulcer recurrence based on the proposed conceptual framework. Results The median time to recurrence was 42 weeks (95% CI 31.9–52.0), with an incidence of 22% (54 of 250 participants) recurrence within three months of healing, 39% (91 of 235 participants) for those who were followed for six months, 57% (111 of 193) by 12 months, 73% (53 of 72) by two years and 78% (41 of 52) of those who were followed up for three years. A Cox proportional-hazards regression model revealed that the risk factors for recurrence included a history of deep vein thrombosis (HR 1.7, 95% CI 1.07–2.67, p=0.024), history of multiple previous leg ulcers (HR 4.4, 95% CI 1.84–10.5, p=0.001), and longer duration (in weeks) of previous ulcer (HR 1.01, 95% CI 1.003–1.01, p<0.001); while the protective factors were elevating legs for at least 30 minutes per day (HR 0.33, 95% CI 0.19–0.56, p<0.001), higher levels of self-efficacy (HR 0.95, 95% CI 0.92–0.99, p=0.016), and walking around for at least three hours/day (HR 0.66, 95% CI 0.44–0.98, p=0.040). Conclusions Results from this study provide a comprehensive examination of risk and protective factors associated with leg ulcer recurrence based on the chronic disease self and family management framework. These results in turn provide essential steps towards developing and testing interventions to promote optimal prevention strategies for venous leg ulcer recurrence.

Raman and infrared spectroscopic characterization of the arsenate-bearing mineral tangdanite– and in comparison with the discredited mineral clinotyrolite

The minerals clinotyrolite and fuxiaotuite are discredited in terms of the mineral tangdanite. The mixed anion mineral tangdanite Ca2Cu9(AsO4)4(SO4)0.5(OH)9 9H2O has been studied using a combination of Raman and infrared spectroscopy. Characteristic bands associated with arsenate, sulphate and hydroxyl units are identified. Broad bands in the OH stretching region are observed and are resolved into component bands. These bands are assigned to water and hydroxyl stretching vibrations. Two intense Raman bands at 837 and approximately 734 cm−1 are assigned to the ν1 (AsO4)3− symmetric stretching and ν3 (AsO4)3− antisymmetric stretching modes. Infrared bands at 1023 cm−1 are assigned to the (SO4)2− ν1 symmetric stretching mode, and infrared bands at 1052, 1110 and 1132 cm−1 assigned to (SO4)2− ν3 antisymmetric stretching modes, confirming the presence of the sulphate anion in the tangdanite structure. Raman bands at 593 and 628 cm−1 are attributed to the (SO4)2− ν4 bending modes. Low-intensity Raman bands found at 457 and 472 cm−1 are assigned to the (AsO4)3− ν2 bending modes. A comparison is made with the previously obtained spectral data on the discredited mineral clinotyrolite.

Experimental evaluation of the performance of 2×2 MIMO-OFDM for vehicle-to-infrastructure communications

In this paper, a novel 2×2 multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) testbed based on an Analog Devices AD9361 highly integrated radio frequency (RF) agile transceiver was specifically implemented for the purpose of estimating and analyzing MIMO-OFDM channel capacity in vehicle-to-infrastructure (V2I) environments using the 920 MHz industrial, scientific, and medical (ISM) band. We implemented two-dimensional discrete cosine transform-based filtering to reduce the channel estimation errors and show its effectiveness on our measurement results. We have also analyzed the effects of channel estimation error on the MIMO channel capacity by simulation. Three different scenarios of subcarrier spacing were investigated which correspond to IEEE 802.11p, Long-Term Evolution (LTE), and Digital Video Broadcasting Terrestrial (DVB-T)(2k) standards. An extensive MIMO-OFDM V2I channel measurement campaign was performed in a suburban environment. Analysis of the measured MIMO channel capacity results as a function of the transmitter-to-receiver (TX-RX) separation distance up to 250 m shows that the variance of the MIMO channel capacity is larger for the near-range line-of-sight (LOS) scenarios than for the long-range non-LOS cases, using a fixed receiver signal-to-noise ratio (SNR) criterion. We observed that the largest capacity values were achieved at LOS propagation despite the common assumption of a degenerated MIMO channel in LOS. We consider that this is due to the large angular spacing between MIMO subchannels which occurs when the receiver vehicle rooftop antennas pass by the fixed transmitter antennas at close range, causing MIMO subchannels to be orthogonal. In addition, analysis on the effects of different subcarrier spacings on MIMO-OFDM channel capacity showed negligible differences in mean channel capacity for the subcarrier spacing range investigated. Measured channels described in this paper are available on request.

Large variations in the Holocene marine radiocarbon reservoir effect reflect ocean circulation and climatic changes

Accurate radiocarbon dating of marine samples requires knowledge of the marine radiocarbon reservoir effect. This effect for a particular site/region is generally assumed constant through time when calibrating marine 14C ages. However, recent studies have shown large temporal variations of several hundred to a couple of thousand years in this effect for a number of regions during the late Quaternary and Holocene. Here we report marine radiocarbon reservoir correction (ΔRΔR) for Heron Reef and Moreton Bay in southwestern (SW) Pacific for the last 8 ka derived from 14C analysis of 230Th-dated corals. Most of our ΔRΔR for the last ∼5.4 ka agree well with their modern value, but large ΔRΔR variability of ∼410 yr (from trough to peak) with possible decadal/centennial fluctuations is evident for the period ∼5.4–8 ka. The latter time interval also has significant variations with similar features in previously published ΔRΔR values for other sites in the Pacific, including southern Peru–northern Chile in southeastern (SE) Pacific, the South China Sea, Vanuatu and Papua New Guinea, with the largest magnitude of ∼920 yr from SE Pacific. The mechanisms for these large ΔRΔR variations across the Pacific during the mid-Holocene are complex processes involving (1) changes in the quantity and 14C content of upwelled waters in tropical east Pacific (TEP) (frequency and intensity of ocean upwelling in the TEP, and contribution of Subantarctic Mode Water to the upwelled waters, which is influenced by the intensity and position of southern westerly winds), and (2) variations in ocean circulation associated with climate change (La Niña/El Niño conditions, intensity of easterly trade winds, positions of the Intertropical Convergence Zone and the South Pacific Convergence Zone), which control the spreading of the older upwelled surface waters in the TEP to the western sites. Our results imply the need for employing temporal changes in ΔRΔR values, instead of constant (modern) values, for age calibration of Holocene marine samples not only for the SW Pacific sites but also for other tropical and subtropical sites in the Pacific.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.

Transcriptome analysis of Neotyphodium and Epichloë grass endophytes

Large-scale gene discovery has been performed for the grass fungal endophytes Neotyphodium coenophialum, Neotyphodium lolii, and Epichloë festucae. The resulting sequences have been annotated by comparison with public DNA and protein sequence databases and using intermediate gene ontology annotation tools. Endophyte sequences have also been analysed for the presence of simple sequence repeat and single nucleotide polymorphism molecular genetic markers. Sequences and annotation are maintained within a MySQL database that may be queried using a custom web interface. Two cDNA-based microarrays have been generated from this genome resource. They permit the interrogation of 3806 Neotyphodium genes (NchipTM microarray), and 4195 Neotyphodium and 920 Epichloë genes (EndoChipTM microarray), respectively. These microarrays provide tools for high-throughput transcriptome analysis, including genome-specific gene expression studies, profiling of novel endophyte genes, and investigation of the host grass–symbiont interaction. Comparative transcriptome analysis in Neotyphodium and Epichloë was performed