Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

An entangled-light-emitting diode.

An optical quantum computer, powerful enough to solve problems so far intractable using conventional digital logic, requires a large number of entangled photons. At present, entangled-light sources are optically driven with lasers, which are impractical for quantum computing owing to the bulk and complexity of the optics required for large-scale applications. Parametric down-conversion is the most widely used source of entangled light, and has been used to implement non-destructive quantum logic gates. However, these sources are Poissonian and probabilistically emit zero or multiple entangled photon pairs in most cycles, fundamentally limiting the success probability of quantum computational operations. These complications can be overcome by using an electrically driven on-demand source of entangled photon pairs, but so far such a source has not been produced. Here we report the realization of an electrically driven source of entangled photon pairs, consisting of a quantum dot embedded in a semiconductor light-emitting diode (LED) structure. We show that the device emits entangled photon pairs under d.c. and a.c. injection, the latter achieving an entanglement fidelity of up to 0.82. Entangled light with such high fidelity is sufficient for application in quantum relays, in core components of quantum computing such as teleportation, and in entanglement swapping. The a.c. operation of the entangled-light-emitting diode (ELED) indicates its potential function as an on-demand source without the need for a complicated laser driving system; consequently, the ELED is at present the best source on which to base future scalable quantum information applications.

Role of information in preparing men for transrectal ultrasound guided prostate biopsy: a qualitative study embedded in the ProtecT trial.

BACKGROUND: The histological diagnosis of prostate cancer requires a prostate needle biopsy. Little is known about the relationship between information provided to prepare men for transrectal ultrasound guided biopsy (TRUS-Bx) and how men experience biopsy. The objectives were a) to understand men's experiences of biopsy as compared to their expectations; and b) to propose current evidence-based information for men undergoing TRUS-Bx. METHODS: Between February 2006 and May 2008, 1,147 men undergoing a standardised 10-core transrectal ultrasound guided biopsy protocol under antibiotic cover following a PSA 3.0-19.9 ng/ml in the Prostate Testing for Cancer and Treatment (ProtecT) trial, completed questionnaires about biopsy symptoms. In this embedded qualitative study, in-depth interviews were undertaken with 85 men (mean age 63.6 yrs, mean PSA 4.5 ng/ml) to explore men's experiences of prostate biopsy and how the experience might be improved. Interview data were analysed thematically using qualitative research methods. Findings from the qualitative study were used to guide selection of key findings from the questionnaire study in developing a patient information leaflet preparing men for biopsy. RESULTS: Although most men tolerated TRUS-Bx, a quarter reported problematic side-effects and anxiety. Side effects were perceived as problematic and anxiety arose most commonly when experiences deviated from information provided. Men who were unprepared for elements of TRUS-Bx procedure or its sequelae responded by contacting health professionals for reassurance and voiced frustration that pre-biopsy information had understated the possible severity or duration of pain/discomfort and bleeding. Findings from questionnaire and interview data were combined to propose a comprehensive, evidence-based patient information leaflet for TRUS-Bx. CONCLUSIONS: Men reported anxiety associated with TRUS-Bx or its side-effects most commonly if they felt inadequately prepared for the procedure. Data from this qualitative study and the previous questionnaire study have been used to propose an updated, comprehensive evidence-based set of information for men undergoing TRUS-Bx.

Living with osteoarthritis: a systematic review and meta-ethnography.

OBJECTIVES: To review and synthesize the existing literature on the experience of living with a diagnosis of hip and/or knee osteoarthritis (OA). METHOD: A systematic review was undertaken using meta-ethnography. A search of both published (AMED, CINAHL, EMBASE, PsychINFO, SportsDisc, MEDLINE, Cochrane Clinical Trials Registry, PubMed) and unpublished/trial registry databases [World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the United States National Institute of Health Trials Registry, National Institute for Health Research (NIHR) Clinical Research Portfolio Database] was undertaken from their inception to 5 June 2013. RESULTS: Thirty-two studies formed the meta-ethnography of the lived experiences of people with OA. In total, 1643 people with OA were sampled, the majority diagnosed with knee OA. The evidence base was weak to moderate in quality. The majority of studies indicated that people viewed living with OA negatively. Four key factors influenced their attitudes to the condition: the severity of their symptoms; the impact of these symptoms on their functional capability; their attitude towards understanding their disease; and their perceptions of other people's beliefs towards their disease. CONCLUSIONS: The current literature suggests that greater knowledge of the pathology of OA, management of symptoms, promotion of functional activity for patients and their family/friends networks, and understanding to better inform OA patient's role in society are all important elements that affect a person's attitude to OA. By better understanding these factors during future consultations, clinicians may forge stronger relationships with their patients to more effectively manage this long-term disabling condition.

How chronic ear disease affects quality of life: a qualitative research study in Nepal.

OBJECTIVE: Hearing loss is the third leading cause globally for 'years lived with disability'. The majority of those affected live in low and middle-income countries. METHOD: This study used qualitative research methods to explore the impact of chronic ear disease on quality of life in Nepal. Twenty face-to-face semi-structured interviews were conducted during a visiting ear camp at the Britain Nepal Otology Service Ear Care Centre in Nepal. Interviews were recorded, transcribed and translated with thematic content analysis performed manually by two researchers. RESULTS: Chronic ear disease has a significant impact on social interactions, emotional well-being and functionality. Barriers to surgery are cost, accessibility, reputation, gender and fear of complications. CONCLUSION: This study provided valuable new insight into patient perspectives on living with chronic ear disease in Nepal. Patients with chronic ear disease experience discrimination and stigmatisation across all levels of personal, family and social life, with their function across all domains being directly limited by symptoms.

Indistinguishable entangled photons generated by a light-emitting diode.

A linear optical quantum computer relies on interference between photonic qubits for logic, and entanglement for near-deterministic operation. Here we measure the interference and entanglement properties of photons emitted by a quantum dot embedded within a light-emitting diode. We show that pairs of simultaneously generated photons are entangled, and indistinguishable from subsequently generated photons. We measure entanglement fidelity of 0.87 and two-photon-interference visibility of 0.60 ± 0.05. The visibility, limited by detector jitter, could be improved by optical cavity designs.

An electrophysiological and spectroscopic study of the properties and structure of biological calcium channels. Investigations of a model ion channel.

The N- and C-terminally protected peptide N-acetyl-Asp-Phe-Ala-Asn-Arg-Val-Leu-Leu-Ser-Leu-Phe-Thr-Ile-Glu-Met-Leu -Leu-Lys-Met-Leu-NH2, closely based on the sequence of the putative S2 membrane spanning helix of domain II of the dihydropyridine receptor calcium channel of the T-system of skeletal muscle, residues 465-486 (Tanabe et al. (1987) Nature 328, 313-318) has been synthesised. Conductance measurements in planar lipid bilayers show that the peptide is capable of inducing the transmembrane passage of calcium and barium ions, in preference to monovalent cations. No anion conductance is observed. 1H-NMR spectroscopy demonstrates that in an amphilic solvent, methanol, the peptide forms highly stable structures characterised by very slow exchange with solvent of peptide N-H protons. Double-quantum filtered phase-sensitive COSY shows that, on the basis of NH-CH alpha scalar coupling constants, most peptide torsion angles are appropriate to an overall alpha-helical conformation; the presence of some alpha-helix is also supported by CD measurements. Most side-chain connectivities have been identified in a DIPSI-TOCSY experiment. This evidence has been used to construct a low-resolution model of the ion-conducting channel of the muscle T-system dihydropyridine receptor from the sequences of the four homologous putative channel-lining stretches. It is characterised by an association of acidic residues at the putative extra-membranous face of the channel, followed by a predominantly hydrophobic band. The next prominent feature of the model is an ordered array of four acidic residues (glutamates 100, 478, 846 and 1164), followed by four lysines (104, 482, 850 and 1168) which may play a gating role.

Purification and secondary structural analysis of tissue inhibitor of metalloproteinases-1.

In connective tissue diseases such as rheumatoid arthritis, the matrix metalloproteinases are the primary enzymes involved in tissue degradation. Tissue inhibitor metalloproteinases-1 (TIMP-1) is a specific inhibitor of these enzymes, which is thought to regulate their action in vivo. The structure and function of TIMP-1 may therefore be important as the basis for the rational design of therapeutic agents. This paper describes a simple and effective method for the purification of sufficient quantities of TIMP-1 for spectroscopic studies. Circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy have, together, showed TIMP-1 to be mostly in a beta-sheet conformation, with significant amounts of alpha-helix and beta-turn. Two-dimensional nuclear magnetic resonance spectroscopy indicated a correspondingly high proportion of beta-sheet. CD and FTIR have also shown TIMP-1 to have high thermostability.

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial.

OBJECTIVES: To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. DESIGN: Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. SETTING: Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. PARTICIPANTS: Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. RESULTS: Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. CONCLUSIONS: The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice. TRIAL REGISTRATION NUMBERS: NCT02044172; ISRCTN20141297.

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

Hydrogen bonding. 47. Characterization of the ethylene glycol-heptane partition system: hydrogen bond acidity and basicity of peptides.

Twelve measured ethylene glycol-heptane partition coefficients, Peh, have been combined with 20 measured literature values and 44 indirectly determined values to give a set of 76 values. Excluding one value for benzamide, the log Peh values are correlated through our general solvation equation, log Peh = 0.336 - 0.075R2 - 1. 201pi2H - 3.786 Sigmaalpha2H - 2.201 Sigmabeta2H + 2.085Vx with r2 = 0.966, sd = 0.28, and F = 386. The solute descriptor R2 is the excess molar refraction, pi2H is the dipolarity/polarizability, Sigmaalpha2H and Sigmabeta2H are the overall hydrogen bond acidity and basicity, and Vx is the McGowan volume. The log Peh equation has then been used to obtain descriptors for eleven peptides, all of which are end-protected. It is shown that for these end-protected peptides, hydrogen bond basicity makes a greater contribution to log Peh than does hydrogen bond acidity.

Multiwavelength spectrophotometric determination of acid dissociation constants: Part III. Resolution of multi-protic ionization systems.

A multiwavelength spectrophotometric (WApH) titration method was applied to study several multi-protic histamine H2-receptor antagonists which involved four acid dissociation constants (pKa values) over the pH range of 2-10. Specifically, UV absorption spectra of the drug solution were acquired in the course of a pH-metric titration using an optical device based on a fibre optics dip probe, a light source and a diode array detector. Target factor analysis was utilized to deduce the pKa values from the spectral data recorded at different pH. It was noted that some of the pKa values were within mid pH range which were difficult to obtain because of insufficient absorption spectra acquired in the un-buffered region of the titration curve. With the aid of the WApH technique coupled with an optically transparent buffer, all pKa values have been successfully determined and were in excellent agreement with those measured using a conventional pH-metric method.

Psychological effects of nuclear and radiological warfare.

Not since 1945 has the world experienced nuclear warfare, although there has been the threat of nuclear terrorism and a large number of nuclear/radiological accidents. Most people fear a nuclear/radiological threat even more than a conventional explosion due both to their inability to perceive the presence of radiation with the ordinary human senses and to concerns about perceived long-lasting radiation effects. Studies of radiological accidents have found that for every actually contaminated casualty, there may be as many as 500 people who are concerned, eager to be screened for contamination, sometimes panicked, and showing psychosomatic reactions mimicking actual radiation effects. Data from the Hiroshima and Nagasaki attacks revealed widespread acute reactions such as psychic numbing, severe anxiety, and disorganized behavior, and there were later chronic effects such as survivor guilt and psychosomatic reactions. Such responses would likely be common in any future nuclear/radiological accident, terrorist attack, or warfare.

Dietary tyrosine as an aid to stress resistance among troops.

In past conflicts battle stress casualties have caused a serious exit of troops from the frontlines. Recent research has linked stress-caused impairments of performance with depletion of brain stores of the neurotransmitter norepinephrine (NE), which functions in neural tracts responding to stress. The amino acid tyrosine (TYR) is the dietary precursor for NE, and supplementation with TYR has been demonstrated in the laboratory to alleviate declines in both neural NE and performance during stress. Thus, TYR supplementation might help to prevent and treat stress casualties in combat. Further research is called for to verify this hypothesis.

Sleep-related injuries in the U.S. Army, 1984-1991.

U.S. Army Safety Center files for the years 1984-1991 were searched for ground accidents involving sleeping soldiers. There were 68 incidents which could be so categorized, 53 of which resulted in injuries and 15 in fatalities. The average cost to the Army, adjusted to 1991 dollars, was $8,300 for each injury and $61,900 for each fatality. The injured required an average 24.6 days of lost duty time for recovery. The incidents most commonly occurred when soldiers slept near vehicles and less commonly when they slept in designated "safe" areas. With improved guidance and training, such accidents could be reduced.

Reproductive performance in South Australian dairy herds.

Herd breeding records (161) were examined from a random 10% sample of dairy farms (96) in South Australia with more than 40 cows and suitable breeding records for 1988 and/or 1989. Of these farms, 53 (55.2%) had a year-round calving pattern, 42 (43.8%) claimed to be seasonal and one was changing from a year-round to a seasonal pattern. Only 14.6% of farmers observed oestrous behaviour outside milking times and 18.8% used tailpaint. Overall, the average proportion of unobserved heats was estimated to be 32%. Artificial insemination (AI) was carried out on 85.4% of farms (16.7% used AI alone and 68.7% also used bulls) of which 32.9% used commercial technicians and 67.1% were do-it-yourself operators. Overall, the average 30-day submission rate was 59.9% and the average 49-day non-return to service rate was 58.9%. Investigation into the probable causes of suboptimal reproductive performance gave a tentative diagnosis of inefficient oestrous detection, deferral of service, inadequate nutrition, poor AI technique, insufficient bulls, and venereal/other diseases in 69.1, 32.1, 27.2, 28.4, 13.6 and 7.4% of records, respectively.

Automobile color as a predictor of driving behavior.

Research on achievement motivation has shown that highly motivated people prefer cool or somber colors like blue and tend to be in a hurry, while less motivated people tend to choose warm or bright colors like red and are less time conscious. We applied these findings to automobile driving, hypothesizing that drivers of cars with high nACH colors would speed at greater velocities and run red lights and stop signs more. Unobtrusive observation in three studies of 193 highway speeders, 261 cars at stop lights, and 191 cars at stop signs showed that drivers of cars with high nACH colors did tend to speed at higher rates and to run red lights more, although they did not run stop signs more. The data partially support previous research on the behavioral correlates of color preference.

Family planning lessons and challenges. Making programs work.

Over the past 30 years, family planning programs have helped millions of people to have the smaller families that they want. As programs have learned how to meet people's needs, contraceptive use has spread rapidly.

Meeting the needs of young adults.

As they mature and become sexually active, more young people face serious health risks. Most face these risks with too little factual information, too little guidance about sexual responsibility, and too little access to health care. Meeting young adults' diverse needs challenges parents, communities, health care providers, and educators. Despite urgent needs, program efforts have been slight and slowed by controversy.

PIP: The overview of this report, illustrated with tables, discusses the size and proportion of the population ages 10-19; the definition of young adult; the falling age of puberty; sexual activity among young adults (including premarital sexual activity); the rising age at marriage; fertility patterns; contraceptive usage (including factors that inhibit usage, such as a lack of information, of access, of decision-making ability, and/or of power); and unmet contraceptive needs. The report's essay on growth, change, and risk behavior associated with youth deals with the specific topics of sexually transmitted diseases, sexual violence and coercion, the health risks of early pregnancy, unintended pregnancy and the complications of unsafe abortion, the social and economic consequences of early childbearing, and ways to meet needs and, thus, prevent problems. This last subject leads into an overview of programs available for young adults, including large school programs, small health programs, and European youth programs and social norms. A table gives types of reproductive health programs for young adults that defines the audience/activities, extent of the program, special issues addressed, and research findings for 1) family life education programs, 2) clinic-based programs, 3) AIDS prevention programs, 4) condom distribution programs, 5) school clinics, 6) communication through the entertainment media, and 7) peer education. In the next major section of the report, evaluations of the various types of programs for youth are reviewed to determine whether the programs lead to a delay in initiation of sexual intercourse, an increase in sexual intercourse, and/or an increase in contraceptive usage. Consideration is then given to what makes programs work and how to win support for programs from the community and from young adults. These major essays are punctuated with short highlights on such topics as whether adults and youth have differing views about sex behavior, whether young people are different today than they were in the past, reaching boys with services, where young people learn about sex, contraceptive choices for youth, and lessons learned from youth programs.

Psychological impact of prostate biopsy: physical symptoms, anxiety, and depression.

PURPOSE: To investigate the psychological impact of prostate biopsy, including relationships between physical biopsy-related symptoms and anxiety and depression. PATIENTS AND METHODS: A prospective cohort of 1,147 men, nested within the Prostate Testing for Cancer and Treatment trial and recommended to receive prostate biopsy, completed questionnaires assessing physical and psychological harms after biopsy in the Prostate Biopsy Effects study. Psychological impact was measured using the Hospital Anxiety and Depression Scale, and scores were compared according to experiences of biopsy-related symptoms at biopsy, and at 7 and 35 days afterward, and in relation to biopsy results. RESULTS: A total of 1,144 men (99.7%) returned questionnaires at biopsy, with 1,090 (95.0%) and 1,016 (88.6%) responding at 7 and 35 days postbiopsy. Most men experienced biopsy-related symptoms as no problem or a minor problem, and overall levels of anxiety and depression were low and similar to normative levels. Of men receiving a negative biopsy result (n = 471), anxiety was greater in those experiencing problematic biopsy-related symptoms compared with those experiencing nonproblematic symptoms at 7 days for the following symptoms: pain (P < .001), shivers, (P = .020), hematuria (P < .001), hematochezia (P < .001), and hemoejaculate (P < .001). Anxiety was reduced, although symptoms were not, after 35 days. Overall levels of anxiety were low across all time points except at the 35-day assessment among men who had received a cancer diagnosis. CONCLUSION: Problematic postbiopsy symptoms can lead to increased anxiety, distinct from distress related to diagnosis of prostate cancer. Men and doctors need to consider these additional potential harms of biopsy when deciding whether to initiate prostate-specific antigen testing.