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Background: The Covid-19 pandemic led to a rapid increase in the use of virtual consultations across healthcare. Post-pandemic, this use is expected to continue alongside the resumption of traditional face-to-face clinics. At present, research exploring when to use different consultation formats for palliative care patients is limited., Aim: To understand the benefits and limitations of a blended approach to outpatient palliative care services, to provide recommendations for future care., Methods: A mixed-methods study. Component 1: an online survey of UK palliative care physicians. Component 2: a qualitative interview study exploring patients' and caregivers' experiences of different consultation formats. Findings from both components were integrated, and recommendations for clinical practice identified., Results: We received 48 survey responses and conducted 8 qualitative interviews. Survey respondents reported that face-to-face consultations were appropriate/necessary for physical examinations (n = 48) and first consultations (n = 39). Video consultations were considered appropriate for monitoring stable symptoms (n = 37), and at the patient's request (n = 42). Patients and caregivers felt face-to-face consultations aided communication. A blended approach increased flexibility and reduced travel burden., Conclusions: A blended outpatient palliative care service was viewed positively by physicians, patients and caregivers. We identified 13 clinical practice recommendations for the use of different consultation formats., Competing Interests: Declarations Ethics approval and consent to participate This study has been performed in accordance with the Declaration of Helsinki and was approved by the UK Research Ethics Committee (project ID 308342). I, the submitting author, declare that all methods in this work were carried out in accordance with relevant guidelines and regulations. Consent for publication N/A. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We report on the latest advancements in Microcrystal Electron Diffraction (3D ED/MicroED), as discussed during a symposium at the National Center for CryoEM Access and Training housed at the New York Structural Biology Center. This snapshot describes cutting-edge developments in various facets of the field and identifies potential avenues for continued progress. Key sections discuss instrumentation access, research applications for small molecules and biomacromolecules, data collection hardware and software, data reduction software, and finally reporting and validation. 3D ED/MicroED is still early in its wide adoption by the structural science community with ample opportunities for expansion, growth, and innovation., (open access.)

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world., (open access.)

Three-dimensional electron diffraction (3DED) from nanocrystals of biological macromolecules requires the use of very small crystals. These are typically less than 300 nm-thick in the direction of the electron beam due to the strong interaction between electrons and matter. In recent years, focused-ion-beam (FIB) milling has been used in the preparation of thin samples for 3DED. These instruments typically use a gallium liquid metal ion source. Inductively coupled plasma (ICP) sources in principle offer faster milling rates. Little work has been done to quantify the damage these sources cause to delicate biological samples at cryogenic temperatures. Here, an analysis of the effect that milling with plasma FIB (pFIB) instrumentation has on lysozyme crystals is presented. This work evaluates both argon and xenon plasmas and compares them with crystals milled with a gallium source. A milling protocol was employed that utilizes an overtilt to produce wedge-shaped lamellae with a shallow thickness gradient which yielded very thin crystalline samples. 3DED data were then acquired and standard data-processing statistics were employed to assess the quality of the diffraction data. An upper bound to the depth of the pFIB-milling damage layer of between 42.5 and 50 nm is reported, corresponding to half the thickness of the thinnest lamellae that resulted in usable diffraction data. A lower bound of between 32.5 and 40 nm is also reported, based on a literature survey of the minimum amount of diffracting material required for 3DED., (open access.)

Objective: Postural tachycardia syndrome (PoTS) is a disorder of the autonomic nervous system which involves a range of symptoms, worsened when adopting an orthostatic (upright) position. Symptoms can include tachycardia, dizziness, fainting, nausea as well as many others which, as is typical of a syndrome, vary from person to person. Although research is increasing into this condition, the unifying experiences of managing it on a daily basis have not been extensively investigated. This study aimed to capture participants' experiences of living with PoTS., Method: A longitudinal digital ethnographic approach was employed. Eight participants recorded daily video diaries discussing their experiences of PoTS and its impact for 17 days. Interpretative phenomenological analysis was utilised to analyse the data and identify connections across participants' accounts., Results: Four superordinate themes emerged: 'loss of control and lack of agency over body', 'identity changes', 'lack of understanding from others' and 'adapting to cope with PoTS'., Discussion: The findings demonstrated the complex and widespread impact these participants experience from their PoTS symptoms, including the consequent emotional difficulties that result from managing this condition. An overall lack of understanding about PoTS by others was emphasised, suggesting the requirement for better education and support services for this condition.

Background: Timely administration of 'as-required' medication is important for managing patients' symptoms in palliative care. There are no national or local standards around the maximum length of time for the process to administer 'as-required' medication and little in the literature to inform practice. Our aim was to understand the patient experience of receiving these medications in the in-patient setting of a hospice., Methods: A survey of hospice patients who had been on the ward at least seven days was conducted over a fifteen-week period looking at current practice, the patient experience of requesting medication and how long it took to be administered., Results: Thirty-one responses were obtained. Patients made their requests in a variety of ways but 33% did not use their call bell. When looking at their most recent 'as-required' medication request, 87% of patients estimated that they received it within ten minutes. When considering their longest wait, 16% of patients reported waiting longer than twenty minutes., Conclusion: This survey highlights the importance of there being a variety of ways for patients to request 'as-required' medication and staff being proactive with patients to facilitate these requests. Patients perceive nursing staff to be busy and do not want to bother them. Although usually patients get their medication within ten minutes, patients can be waiting more than twenty minutes. There is a need for national standards on time to administer as-required medication within a healthcare setting and a need for more data to inform such a standard.

In processing X-ray diffraction data, the intensities obtained from integration of the diffraction images must be corrected for experimental effects in order to place all intensities on a common scale both within and between data collections. Scaling corrects for effects such as changes in sample illumination, absorption and, to some extent, global radiation damage that cause the measured intensities of symmetry-equivalent observations to differ throughout a data set. This necessarily requires a prior evaluation of the point-group symmetry of the crystal. This paper describes and evaluates the scaling algorithms implemented within the DIALS data-processing package and demonstrates the effectiveness and key features of the implementation on example macromolecular crystallographic rotation data. In particular, the scaling algorithms enable new workflows for the scaling of multi-crystal or multi-sweep data sets, providing the analysis required to support current trends towards collecting data from ever-smaller samples. In addition, the implementation of a free-set validation method is discussed, which allows the quantification of the suitability of scaling-model and algorithm choices., (open access.)

The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, by means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because of this inherent flexibility, users are often presented with diverse, even divergent, choices for solving every type of problem. Recently, CCP4 introduced CCP4i2, a modern graphical interface designed to help structural biologists to navigate the process of structure determination, with an emphasis on pipelining and the streamlined presentation of results. In addition, CCP4i2 provides a framework for writing structure-solution scripts that can be built up incrementally to create increasingly automatic procedures.

Dysphagia and weight loss are experienced by up to 80% of patients with motor neuron disease (MND). Enteral tube feeding can benefit these patients but side effects including fullness, bloating, diarrhoea and constipation are frequent and can lead to non-compliance. Changes in feed formulation, regimens and the use of prokinetic medication can help symptoms. We describe a case where the use of gastric pressure relief bags during enteral feeding improved symptoms of bloating in a hospice inpatient with MND. Symptoms recurred when these were not used, which were only partially relieved by manual venting of the gastrostomy tube. We suggest that this simple, non-pharmacological approach to bloating may provide opportunities for symptom relief in the palliative care setting., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The mastocytoses comprise a group of proliferative stem cell disorders defined by the abnormal accumulation of mast cells (MCs) in the skin or other body tissues including the bone marrow, gastrointestinal tract, and liver. Systemic mastocytosis is defined by the presence of one major and one minor criterion or 3 minor criteria delineated by the World Health Organization (WHO). We present the case of a 57-year-old woman with a 10-year history of red-brown pruritic maculopapular lesions on the upper and lower extremities and trunk who was originally diagnosed with cutaneous mastocytosis. Symptoms had been adequately controlled with a combination of topical corticosteroids and antihistamines. After 9 years of controlled disease, the patient presented with increasingly severe breakthrough pruritus and new skin lesions on the head and neck. Further workup included bone marrow biopsy, which demonstrated dense mastocyte infiltrates without evidence of functional impairment, and elevated serum tryptase levels. Narrowband UVB (NB-UVB) phototherapy was initiated, and after 20 treatments the patient reported a marked decrease in symptoms. This case provides evidence of the efficacy of NB-UVB phototherapy in managing patients with long-standing indolent systemic mastocytosis (ISM) who have stopped responding adequately to topical corticosteroids and antihistamines.

Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein's function by altering its energy landscape. Here, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre-steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disrupted in the clinical T315I resistance mutation. This work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve., (Copyright © 2015, American Association for the Advancement of Science.)

We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Insomnia is prevalent, severe and partially heritable. Unfortunately, its neuronal correlates remain enigmatic, hampering the development of mechanistic models and rational treatments. Consistently reported impairments concern fragmented sleep, hyper-arousal and executive dysfunction. Because fronto-striatal networks could well play a role in sleep, arousal regulation and executive functioning, the present series of studies used an executive task to evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia showed reduced recruitment of the head of the left caudate nucleus during executive functioning, which was not secondary to altered performance or baseline perfusion. Individual differences in caudate recruitment were associated with hyper-arousal severity. Seed-based functional connectivity analysis suggested that attenuated input from a projecting orbitofrontal area with reduced grey matter density contributes to altered caudate recruitment in patients with insomnia. Attenuated caudate recruitment persisted after successful treatment of insomnia, warranting evaluation as a potential vulnerability trait. A similar selective reduction in caudate recruitment could be elicited in participants without sleep complaints by slow-wave sleep fragmentation, providing a model to facilitate investigation of the causes and consequences of insomnia.

Protein misfolding is a universal threat to cells. The ubiquitin-proteasome system mediates a cellular stress response capable of eliminating misfolded proteins. Here we identify Cuz1/Ynl155w as a component of the ubiquitin system, capable of interacting with both the proteasome and Cdc48. Cuz1/Ynl155w is regulated by the transcription factor Rpn4, and is required for cells to survive exposure to the trivalent metalloids arsenic and antimony. A related protein, Yor052c, shows similar phenotypes, suggesting a multicomponent stress response pathway. Cuz1/Ynl155w functions as a zinc-dependent ubiquitin-binding protein. Thus, Cuz1/Ynl155w is proposed to protect cells from metalloid-induced proteotoxicity by delivering ubiquitinated substrates to Cdc48 and the proteasome for destruction.

The ubiquitin-proteasome system is the major pathway for selective protein degradation in eukaryotes. Despite extensive study of this system, the mechanisms by which proteasome function and cell growth are coordinated remain unclear. Here, we identify Spg5 as a novel component of the ubiquitin-proteasome system. Spg5 binds the regulatory particle of the proteasome and the base subassembly in particular, but it is excluded from mature proteasomes. The SPG5 gene is strongly induced in the stationary phase of budding yeast, and spg5Δ mutants show a progressive loss of viability under these conditions. Accordingly, during logarithmic growth, Spg5 appears largely dispensable for proteasome function, but during stationary phase the proteasomes of spg5Δ mutants show both structural and functional defects. This loss of proteasome function is reflected in the accumulation of oxidized proteins preferentially in stationary phase in spg5Δ mutants. Thus, Spg5 is a positive regulator of the proteasome that is critical for survival of cells that have ceased to proliferate due to nutrient limitation.

Palliative care exists in a variety of settings and palliative care teams form many guises within this. A Palliative Medicine Outpatient Clinic (PMOC) exists to meet the flexible provision of the needs and preferences of individuals within whatever care setting they reside. This explorative study used a qualitative methodology, capturing patients' actual experience of care in preference to their satisfaction, as this is a more accurate measure of how and what patients judge as important in their healthcare. The overall themes in this paper point to the 'value' that patients perceived from attending the PMOC and how important the clinics were to clinicians that provided the care. The clinic facilitates much more than symptom control and here lies the challenge in how we convert the very positive experience of individuals into a language of outcome measures that captures the 'essence' of our work in this fiscally driven health economy.

Current methods for diffraction-spot integration from CCD area detectors typically underestimate the errors in the measured intensities. In an attempt to understand fully and identify correctly the sources of all contributions to these errors, a simulation of a CCD-based area-detector module has been produced to address the problem of correct handling of data from such detectors. Using this simulation, it has been shown how, and by how much, measurement errors are underestimated. A model of the detector statistics is presented and an adapted summation integration routine that takes this into account is shown to result in more realistic error estimates. In addition, the effect of correlations between pixels on two-dimensional profile fitting is demonstrated and the problems surrounding improvements to profile-fitting algorithms are discussed. In practice, this requires knowledge of the expected correlation between pixels in the image.

The widely-used blood anticoagulants citrate and EDTA give rise to prominent peaks in (1)H NMR spectra of plasma samples collected in epidemiological and clinical studies, and these cause varying levels of interference in recovering biochemical information on endogenous metabolites. To investigate both the potential metabolic information loss caused by these substances and any possible inter-molecular interactions between the anticoagulants and endogenous components, the (1)H NMR spectra of 40 split human plasma samples collected from 20 individuals into either citrate or EDTA have been analysed. Endogenous metabolite peaks were selectively obscured by large citrate peaks or those from free EDTA and its calcium and magnesium complexes. It is shown that the endogenous metabolites that give rise to peaks obscured by those from EDTA or citrate almost invariably also have other resonances that allow their identification and potential quantitation. Also, metabolic information recovery could be maximised by use of spectral editing techniques such as spin-echo, diffusion-editing and J-resolved experiments. The NMR spectral effects of any interactions between the added citrate or EDTA and endogenous components were found to be negligible. Finally, identification of split samples was feasible using simple multivariate statistical approaches such as principal components analysis. Thus even when legacy epidemiological plasma samples have been collected using the NMR-inappropriate citrate or EDTA anticoagulants, useful biochemical information can still be recovered effectively.

There is little evidence to support tube feeding in advanced dementia although it is still frequently used in acute hospital settings. Patients present with complex problems and are often unable to make decisions about their healthcare needs. Multidisciplinary teams may be challenged by the difficult ethical decisions they are required to make in the best interests of their patients. This paper guides decision making in the management of patients with dementia and dysphagia in the acute hospital setting. A structured approach to information gathering, assessment and management is outlined with practical application of recent published guidelines and research evidence, which ensures appropriate individualised care.

A collaborative project between two Structural Proteomics In Europe (SPINE) partner laboratories, York and Oxford, aimed at high-throughput (HTP) structure determination of proteins from Bacillus anthracis, the aetiological agent of anthrax and a biomedically important target, is described. Based upon a target-selection strategy combining ;low-hanging fruit' and more challenging targets, this work has contributed to the body of knowledge of B. anthracis, established and developed HTP cloning and expression technologies and tested HTP pipelines. Both centres developed ligation-independent cloning (LIC) and expression systems, employing custom LIC-PCR, Gateway and In-Fusion technologies, used in combination with parallel protein purification and robotic nanolitre crystallization screening. Overall, 42 structures have been solved by X-ray crystallography, plus two by NMR through collaboration between York and the SPINE partner in Utrecht. Three biologically important protein structures, BA4899, BA1655 and BA3998, involved in tRNA modification, sporulation control and carbohydrate metabolism, respectively, are highlighted. Target analysis by biophysical clustering based on pI and hydropathy has provided useful information for future target-selection strategies. The technological developments and lessons learned from this project are discussed. The success rate of protein expression and structure solution is at least in keeping with that achieved in structural genomics programs.

Electrically induced birefringence is increasingly used as a fast procedure to characterise the size, shape, polarisation and charge parameters of colloids and their interactions. By considering the optical apparatus generally used, attention is drawn to the significant errors that can arise in such experiments if optical component selection and setting are not critically considered.

Proteins of the Imp4/Brix superfamily are involved in ribosomal RNA processing, an essential function in all cells. We report the first structure of an Imp4/Brix superfamily protein, the Mil (for Methanothermobacter thermautotrophicus Imp4-like) protein (gene product Mth680), from the archaeon M. thermautotrophicus. The amino- and carboxy-terminal halves of Mil show significant structural similarity to one another, suggesting an origin by means of an ancestral duplication. Both halves show the same fold as the anticodon-binding domain of class IIa aminoacyl-tRNA synthetases, with greater conservation seen in the N-terminal half. This structural similarity, together with the charge distribution in Mil, suggests that Imp4/Brix superfamily proteins could bind single-stranded segments of RNA along a concave surface formed by the N-terminal half of their beta-sheet and a central alpha-helix. The crystal structure of Mil is incompatible with the presence, in the Imp4/Brix domain, of a helix-turn-helix motif that was proposed to comprise the RNA-binding moiety of the Imp4/Brix proteins.

An overview is presented of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), the two major hyphenated techniques employed in metabolic profiling that complement direct 'fingerprinting' methods such as atmospheric pressure ionization (API) quadrupole time-of-flight MS, API Fourier transform MS, and NMR. In GC/MS, the analytes are normally derivatized prior to analysis in order to reduce their polarity and facilitate chromatographic separation. The electron ionization mass spectra obtained are reproducible and suitable for library matching, mass spectral collections being readily available. In LC/MS, derivatization and library matching are at an early stage of development and mini-reviews are provided. Chemical derivatization can dramatically increase the sensitivity and specificity of LC/MS methods for less polar compounds and provides additional structural information. The potential of derivatization for metabolic profiling in LC/MS is demonstrated by the enhanced analysis of plant extracts, including the potential to measure volatile acids such as formic acid, difficult to achieve by GC/MS. The important role of mass spectral library creation and usage in these techniques is discussed and illustrated by examples.

Objective: We evaluated the feasibility of a new instrument for continuous fetal pulse oximetry during labor. The measuring sensor can be placed on the fetal back before or after rupture of membranes., Methods: One hundred adult women who had completed 32 weeks of gestation and had an anticipated duration of labor greater than 30 minutes were included in the study. Patients with premature rupture of membranes for 24 hours or more, low placental localization, placenta previa or abruption, vaginal bleeding, acute infection, polyhydramnios, oligohydramnios, or uterine or congenital abnormalities were excluded., Results: All sensors were placed successfully. The mean continuous recording time was 276 minutes. Peripheral oxygen saturation as measured by pulse oximeter values were obtained during a median of 64.05% of the recording time. No chorioamnionitis or endometritis was noted., Conclusion: The new sensor instrumentation was safe for mother and fetus and was well accepted by parents and physicians.

Micro-scale sealed vessel thermal desorption-gas chromatography-mass spectrometry (MSSV-TD-GC-MS) has been applied to the analysis of airborne particulate matter using the US NIST Standard Reference Material (SRM1649a) urban dust. We make qualitative comparisons with open system desorption and illustrate that caution should be used when using the technique without an open system comparison. We report linear responses over the same particulate mass range (1-5 mg) and good reproducibility [SD< or =0.62 mg kg(-1) (< or = 11%)]. We show linearity for a series of 10 n-alkanes and 10 polycyclic aromatic hydrocarbons (PAHs) in the SRM. The technique is also shown to be quantifiable (PAH concentrations typically 4-6 mg kg(-1)).

A thermal desorption GC/MS technique has been developed for the quantification of polycyclic aromatic hydrocarbons (PAHs) in airborne particulate matter using the NIST Standard Reference Material (SRM1649a) Urban Dust. The technique was developed using standard linearity tests in order to establish optimum sample weights and optimum desorption and chromatographic parameters. This direct analysis technique eliminates the use of solvents in the sample preparation (reducing volatile component losses) and also significantly reduces the sample preparation time (no extraction procedure). The technique has been shown to give linearity in terms of the overall TIC response as well as for a prominent series of n-alkanes (C20-C33) and 10 NIST priority PAHs, 8 of which have been quantified. The technique is reported to be uniquely sensitive (PAH concentrations 2-6 mg kg(-1)) and reproducible (MW = 178-228 SD < or =0.228 mg kg(-1), < or =7%; MW = 252 SD < or =0.922 mg kg(-1), < or =33%) over the range of sample weights (1-5 mg). Such sample weights illustrate that the technique can be equally applied to the analysis of airborne particulate samples collected over short time periods (24-48 h) using only commonly used low-volume collection devices.

Several recent experiments have reported that chronic treatment with bovine somatotropin (bST) increased the number of days open without affecting the services per conception. The physiological basis for these effects was examined. Eleven lactating Holstein cows received daily injections of bST (40 mg) and 10 received daily injections of vehicle. Treatment was initiated between 32 and 85 d post partum and continued for up to 180 d. Eight of 11 bST-treated cows experienced at least one period of extended ovarian acyclicity during treatment. Only 3 of 10 control cows did so (P = 0.05). Concentrations of progesterone during luteal phases were lower in bST-treated cows than in controls (P = 0.06). Baseline concentrations of LH were suppressed in bST-treated cows compared with those of controls (P < 0.04). Neither the pulse frequency of LH nor the expression of estrous behavior was affected by bST (P > 0.30). These results indicate that chronic administration of a high dose of bST can reduce reproduction performance by promoting ovarian acyclicity.

Eighteen multiparous Holstein cows were assigned randomly to three treatments at the beginning of the dry period (8 wk before expected parturition). Treatments were: 1) the basal diet containing 5.5 ppm of Cu (control), 2) the basal diet supplemented with 10 ppm of Cu, and 3) the basal diet supplemented with 20 ppm of Cu. The objectives were to measure the changes of Cu and other trace mineral element concentrations in blood and liver from the onset of the dry period (approximately 8 wk prepartum) to 8 wk postpartum and to assess the requirement of Cu during this time. Liver Cu concentration in the control group declined continuously during the 8-wk dry period, and the nadir occurred at parturition. This decline was prevented by dietary Cu supplementation of 10 or 20 ppm. Liver Cu concentration in the control group started to increase slowly after the dramatic decline. Liver Zn concentration changed cubically as a function of week during the treatment period. Plasma Cu and Zn exhibited a quadratic pattern as a function of week. The plasma Cu concentration was lowest 5 wk prior to parturition.

This article focuses attention on the perennial issue of home versus laboratory recording situations for the garnering of dream reports. Studies into the experimental control over procedures for both waking and interviewing are reviewed. Against this background, an experiment into the relationship between REM/NREM sleep and visual imagery is reported. We found that, having corrected for total word count, visual imagery still made an independent contribution to REM reports. This finding is evaluated in the light of differential cognitive mechanisms underlying dream formation during sleep.

EEG spectral power was studied during periods of rapid eye movements (REMs) and tonic intervals in REM sleep of 7 young and 7 older male subjects. Significant symmetrical decreases in alpha and beta1 power at central and occipital sites, concurrent with an increase in frontal theta power, were observed during the production of REMs. The former findings are discussed as sleep analogues to changes in alpha and beta1 during waking, showing increased information processing and behavioural activation, and that of theta is tentatively presented as reflecting an increase in afferent thresholds. Independent of the phasic-tonic REM distinction, total EEG power markedly decreased as a function of time of night and did not interact with age. Significant age differences in the overall spectral composition of the EEG were obtained, namely, a lower level of delta power and a relative shift towards more power in frequencies above 12 Hz for the older group. Further, older subjects also demonstrated a more uniform topographical distribution of alpha and sigma power.

Two experiments were conducted to examine the effects of Cu status on neuroendocrine regulation of LH secretion in dairy steers. In Experiment 1, 18 Holstein steers were assigned randomly to treatment groups in a completely randomized design. Treatments consisted of basal diet alone (control) or supplemented with 5 ppm of Mo or with 20 ppm of Cu. At 8 and 16 wk, Cu concentrations in liver were higher in the group receiving Cu and lower in the group receiving Mo than in the control. Pulse frequencies of LH were not affected by any treatment. Serum LH concentration at 16 wk tended to be lower in the group receiving Mo than in either the control or the group receiving Cu. The ability of the pituitary gland to release LH in response to GnRH was not affected at 17 wk. Concentrations of LH in the pituitary glands were lower in the group receiving Mo than in that receiving Cu or in the controls. No differences in Cu or Mo concentrations were observed in pituitary, median eminence, or hypothalamic tissues. In Experiment 2, 12 Holstein steers were assigned to treatment groups receiving the basal diet supplemented with either 20 ppm or Cu or with 10 ppm of Mo. Spontaneous and GnRH-induced secretion of LH were not influenced by treatments after 8 mo of experiment. Reduction in Cu status has little effect on the endogenous secretion of LH in dairy steers.

The present report concerns the first study in which electrooculographic (EOG) contamination of electroencephalographic (EEG) recordings in rapid eye movement (REM) sleep is systematically investigated. Contamination of REM sleep EEG recordings in six subjects was evaluated in the frequency domain. REM-active and REM-quiet series were obtained for each subject. Transfer coefficients and power spectra of EOG and EEG indicated that (a) increases in transfer coefficients beyond 4.5 Hz are brought about by residual EEG in the EOG, and (b) EOG-EEG contamination in the delta band is most pronounced in frontal, intermediate in central and negligible in occipital leads. It was found that correction of the REM-active series resulted in significant (c) reductions in power, (d) increases in interhemispheric coherences and (e) reductions in degree of lateral asymmetry. These effects were largest for frontal leads, but still marked for central ones. The results are discussed in the light of previous findings concerning models of hemispheric functioning during REM sleep.

This study investigated the influence of aging on memory for home drams and the extent to which cognitive variables such as visual memory, visuospatial IQ, and verbal IQ could account for possible differences herein. Subjects were 80 men and women of ages 45 to 75 years. Memory for dreams was measured by narrative length and frequency of recall. With respect to both measures no significant age differences were noted. Over-all differences in dream recall seemed best explained by visual memory scores. Partial correlational analyses, however, indicated that the small age differences memory or on any of the other cognitive variables. Dream contents were scored for aggression, friendliness, emotion, activities, and the number of characters and objects. The incidence of emotions among women appeared to be lower beyond the age of 60. Comparisons with previous data for young adults indicated that large reductions in aggression, friendliness, and emotion occur before the age of 45.

Twelve Holstein steers in a completely randomized block design were fed either a basal diet (concentrate:silage or hay at a DM ratio of 35:65) plus Cu sulfate at 20 ppm of Cu (Cu-supplemented diet) or a basal diet plus ammonium molybdate to obtain 10 ppm of Mo (Cu-depleting diet) on a DM basis in the whole diet for 8 mo. Supplemental Mo was utilized in the Cu-depleting diet to develop a Cu-deficient group. Molybdenum slowly accumulated in the liver in the group fed the Cu-depleting diet. Copper concentrations in the liver and polymorphonuclear neutrophils decreased in the Cu-deficient group compared with the Cu-sufficient group. Plasma Cu concentration did not change during the trial for the Cu-sufficient group. In the Cu-deficient group, plasma Cu concentrations increased during the first 3 mo of the trial, then declined, and remained unchanged for the last 5 mo. Superoxide dismutase activities in red blood cells, polymorphonuclear neutrophils, and whole blood decreased in the Cu-deficient group. Phagocytic capacity was not affected by Cu status, but killing capacity was decreased by low Cu status in the Cu-deficient group by the end of the trial. Glutathione peroxidase activity was unaffected by Cu status. Clinical symptoms of Cu-deficiency were not observed in this trial; there was no evidence of blood hemoglobin or BW gain difference between the two groups. In this study, Cu status affected its distribution in the tissues and related enzyme activities as well as bactericidal function of neutrophils.

Twenty-four Holstein and Jersey calves (14 Holstein), 4 to 11 d of age, were assigned randomly to six treatments in a 2 x 3 factorial arrangement to examine the effects of Cu sources and dietary cation-anion balance on Cu availability and acid-base balance. Treatments were cationic basal diet (20 meq of dietary cation-anion balance on a DM basis), cationic basal diet supplemented with CuO, cationic basal diet supplemented with CuSO4, anionic basal diet (-10 meq), anionic basal diet supplemented with CuO, and anionic basal diet supplemented with CuSO4. Copper sources did not show any effect on growth of calves. The cationic diet increased calf growth compared with the anionic diet at wk 12 of the experiment. Blood pH was increased by the cationic diet in comparison with the anionic diet at wk 8 and 12. Blood pH also was increased by CuSO4 compared with CuO treatment in the early period of the treatment. Blood bicarbonate concentration was decreased by CuO and the anionic diet. Interactions between Cu sources and cation-anion balance were found for blood pH and bicarbonate concentration. Liver Cu concentration was increased by CuSO4 but not by CuO supplementation compared with control. Therefore, CuSO4 was found to be highly available, whereas CuO was a very poorly available source of Cu for young calves.

Eight midlactation Holstein cows (four primiparous) were assigned to replicated 4 x 4 Latin squares with a 2 x 2 factorial arrangement of treatments. The basal diet was formulated to contain 0 milliequivalents (Na + K) - Cl/100 g of diet DM. Treatment diets of high and low dietary cation-anion balance were achieved by adding appropriate amounts of supplemental Na + K (added on an equivalent basis) or Mg to the basal diet. Milk and protein yield were increased as well as DMI and FCM for Na + K diets The high concentration of cation increased milk fat percentage. The cation-anion balance (using Mg as a cation) had no effect on any of the production parameters observed. The higher cation-anion balances increased blood bicarbonate levels and plasma Na. Urinary Ca excretion was increased for the Mg diets. Urinary pH increased with both the source of cation (Na + K) and the concentration of cation (high) in the diet. other minerals were unaffected in milk, plasma, or urine. Responses measured in this trial reflect treatments calculated using the equation milliequivalents (Na + K) - Cl/100 g diet DM or (Na + K) - (Cl + S)/100 g diet DM, suggesting that Mg plays a minor role in dietary cation-anion balance.

Ten Holstein cows averaging 120 d in lactation were arranged in replicated 5 x 5 Latin squares with 3-wk periods to evaluate the role of sulfur (S) in the dietary cation-anion balance equation. Diets were based on corn silage in Exp. 1 and sorghum silage in Exp. 2. Supplemental S and chloride (Cl) from the double sulfate of potassium and magnesium and CaCl2 were used to manipulate dietary cation-anion balance from 0 to +30 meq when expressed as meq [(Na + K)-(Cl + S)]/100 g diet DM and from +19 to +49 meq when expressed as meq [(Na + K)-Cl]/100 g diet DM. Blood pH was not affected by cation-anion balance, although both S and Cl supplementation tended to lower pH. Blood HCO3- and urine pH decreased and plasma calcium (Ca) and urinary Ca excretion increased as anion was added to the diet. Milk fat production tended to be increased by the low S supplementation. Dietary Cl and S had similar effects on acid-base status. Therefore, we suggest that S be included with Cl in the dietary cation-anion balance equation for lactating dairy cows as follows: meq [(Na + K)-(Cl + S)]/100 g diet DM. Although response of acid-base status to S and Cl was similar, as more data comparing the acidogenicity of S vs Cl become available, it may be necessary to include a modifying coefficient for S in the equation to adjust for differences between S and Cl in acid-generating potential. This coefficient may be further dependent on the dietary source of S.

A brother and sister with Tel Hashomer camptodactyly and mitral valve prolapse are described. Mitral valve prolapse is heterogenous, but appears to occur more frequently in individuals with connective tissue disorders. The presence of mitral valve prolapse as a component manifestation of Tel Hashomer camptodactyly suggests that abnormal connective tissue is a pleiotropic effect of the mutant allele.

Under the influence of an electric field, vesicles in suspension partially deform or orientate, rendering the medium optically birefringent. The amplitudes of the birefringence under fields of variable amplitude lead to evaluation of the anisotropy of the electrical delta alpha and optical delta G polarisabilities of the vesicles. By using pulsed fields, rates of establishment and decay of birefringence enable vesicle sizes d to be measured. Samples of 9:1 phosphatidylcholine-phosphatidylserine liposome suspension in water were studied in the presence of various additives, including sucrose, an antibiotic (streptomycin), a steroid (dexamethasone), an anaesthetic (lignocaine) and a fluidising agent (benzyl alcohol). The changes in the three parameters delta alpha, delta G and d were different for each additive and are thought to be indicative of the mode of interaction of each. Electric birefringence also appears to be a rapid means of detecting structure changes.

The localization theorems for Fourier series of functions of a single variable are classical and easy to prove. The situation is different for Fourier series of functions of several variables, even if one restricts consideration to rectangular, in particular square, partial sums. We show that the answer to the problem can be obtained by considering the notion of generalized bounded variation, which we introduced. Given a nondecreasing sequence {lambda(n)} of positive numbers such that Sigma 1/lambda(n) diverges, a function g defined on an interval I of R(1) is said to be of Lambda-bounded variation (LambdaBV) if Sigma|g(a(n)) - g(b(n))|/lambda(n) converges for every sequence of nonoverlapping intervals (a(n), b(n)) [unk]I. If lambda(n) = n, we say that g is of harmonic bounded variation (HBV). The definition suitably modified can be extended to functions of several variables. We show that in the case of two variables the localization principle holds for rectangular partial sums if LambdaBV = HBV, and that if LambdaBV is not contained in HBV, then the localization principle does not hold for LambdaBV even in the case of square partial sums.

A food preference survey, consisting of 378 food names, was administered to approximately 3,900 personnel of the U.S. Army, Navy, Air Force, and Marine Corps. The survey required the respondent to indicate how much he liked each food (hedonic scale) and how often he wanted it served (preferred frequency scale). Overall, food preferences showed relative popularity of beverages, breakfast foods, and entrées, unpopularity of soups and vegetables, and moderate popularity of the other food classes. Items of particularly high or low preference are statistically identified within each food class. The collection and presentation of these data are intended to assist menu planners of the Armed Forces, as well as others interested in this age group (young men under twenty-six years of age.

In an attempt to obviate the need for intravenous fluids by preventing dehydration, 57 adult volunteers who experienced induced clinical cholera during a vaccine development programme were treated from the onset of diarrhoea with oral glucose-electrolytes therapy. 44 individuals with mild to moderately profuse diarrhoea (less than 8 L. total volume) were maintained in normal water and electrolyte balance with oral therapy alone. 13 individuals with severe diarrhoea (greater than 8 L. total volume) could not be maintained in balance with oral therapy alone, due chiefly to emesis during the first day of illness. Emesis occurred in the absence of significant dehydration or acidosis. Since emesis precludes effective early oral therapy in severe cases, domiciliary oral therapy is unlikely to eliminate cholera mortality. Rural diarrhoea treatment centres using oral therapy with limited amounts of intravenous fluids when needed, could reduce case fatality from cholera and related diarrhoeas virtually to zero with least expense.

Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.

Twenty-four cows each in two trials were paired on age, stage of lactation, and projected milk production to compare the incidence of mastitis with milking two or three times per day over 12 wk. Teats of all cows were dipped daily in a suspension of Streptococcus agalactiae (one of two strains). Average daily milk production for the combined trials was 24.0 kg for the thrice daily group and 22.0 kg for the twice daily group. Quarter foremilk samples were taken every 2 wk for somatic cell counts and bacterial isolations. Somatic cell counts of cows milked twice per day averaged 31 x 10(3) per milliliter compared to 26 x 10(3) for three milkings. There were no significant differences in numbers of new bacterial infections between groups. Cows milked twice per day had 41 new infections and 7 clinical infections and the three-time group had 39 new infections and 2 clinical infections. The many corynebacteria infections were related to the experimental design in which no disinfectant teat dip was used. Three milkings per day did not affect udder health.

An influenza A virus recombinant bearing the surface antigens of the A/Alaska/6/77 (H3N2) wild type virus ands the two ts genes of the A/Udorn/72-ts-1A2 (H3N2) virus was evaluated for attenuation, antigenicity, and transmissibility in 28 adult volunteers all of whom possessed a preinoculation serum hemagglutination-inhibiting (HAI) antibody titer of less than or equal to 1:8 and 18 of whom also possessed a serum neuraminidase-inhibiting (NI) antibody titer of less than or equal to 1:4. The Alaska/77-ts-1A2 recombinant, which had a 37 degrees C shutoff temperature for plaque formation and ts mutations on the genes thought to code for the P1 and P3 polymerase proteins, infected 71 percent of the vaccinees when administered at a dose of 10(6.5) TCID50. Only 3 percent of the vaccinees developed symptoms in contrast to 50 percent of volunteers who received 10(4.2) TCID50 of wild type virus. Vaccinees shed virus for a shorter interval and at a lower titer than the volunteers who received wild type virus. Each ts-1A2 isolate retained the ts phenotype indicating that the recombinant was stable genetically in seronegative adults. An immunological response, as measured by a rise in serum HAI and/or NI antibody, was detected in 71 percent of the vaccinees and 87 percent of the recipients of wild type virus. Transmission of vaccine virus to susceptible contacts was not observed. The two ts-1A2 ts genes have now been transferred to two variants within the H3N2 subtype, the Vic/75 and Alaska/77 viruses, and have rendered the viruses satisfactorily attenuated for adults. The level of infectivity of the Alaska/77-ts-1A2 virus appeared to be low, however.

We report on a family in which the propositus and two distant relatives have a wide nose, broad philtrum, and short columella, a fusion defect of the medial nasal processes. This anomaly resembles potato nose [Benjamins and Stibbe, Acta Otolaryngol 11:274-284, 1927] and bifid nose [Anyane-Yeboa et al, Am J Med Genet 17:561-563, 1984], which are also fusion anomalies of the medial nasal processes. Potato nose is an autosomal dominant trait, whereas bifid nose is likely heterogeneous. In this family autosomal recessive inheritance is likely, therefore suggesting that anomalies of the medial nasal processes are causally heterogeneous and represent a developmental field defect.

Three enteropathogenic Escherichia coli (E.P.E.C.) strains (O127:K63:H6, O128:K67:H2, and O142:K86:H6) isolated from outbreaks of infantile diarrhoea and one strain from the "normal" colonic flora (E. coli HS) of a healthy adult were fed in doses of 10(6), 10(8), and 10(10) organisms in NaHCO3 to adult volunteers. The strains, which had been stored for 7--9 years, gave negative results in sensitive tests for heat-labile (L.T.) enterotoxin (Y-1 adrenal-cell test), heat-stable (S.T.) enterotoxin (infant mouse assay), invasiveness (guineapig eye test), and gross fluid accumulation (infant rabbit assay). Two strains (O142 and O127) caused diarrhoea. L.T. or S.T. enterotoxins were not found in E. coli stool isolates from individuals with diarrhoea and no one had a rise in L.T. antitoxin titre; the findings suggest that L.T. and S.T. enterotoxins were not involved in pathogenesis of the diarrhoea. Non-invasive E.P.E.C. strains probably induce diarrhoea by a mechanism (presumably an enterotoxin) distinct from L.T. or S.T. enterotoxins.