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Background Intra-abdominal hypertension (IAH) is common in critically ill patients and is associated with increased morbidity and mortality. High positive end-expiratory pressures (PEEP) can reverse lung volume and oxygenation decline caused by IAH, but its impact on alveolar overdistension is less clear. We aimed to find a PEEP range that would be high enough to reduce atelectasis, while low enough to minimize alveolar overdistention in the presence of IAH and lung injury. Methods Five anesthetized pigs received standardized anesthesia and mechanical ventilation. Peritoneal insufflation of air was used to generate intra-abdominal pressure of 27 cmH2O. Lung injury was created by intravenous oleic acid. PEEP levels of 5, 12, 17, 22, and 27 cmH2O were applied. We performed computed tomography and measured arterial oxygen levels, respiratory mechanics, and cardiac output 5 min after each new PEEP level. The proportion of overdistended, normally aerated, poorly aerated, and non-aerated atelectatic lung tissue was calculated based on Hounsfield units. Results PEEP decreased the proportion of poorly aerated and atelectatic lung, while increasing normally aerated lung. Overdistension increased with each incremental increase in applied PEEP. “Best PEEP” (respiratory mechanics or oxygenation) was higher than the “optimal CT inflation PEEP range” (difference between lower inflection points of atelectatic and overdistended lung) in healthy and injured lungs. Conclusions Our findings in a large animal model suggest that titrating a PEEP to respiratory mechanics or oxygenation in the presence of IAH is associated with increased alveolar overdistension.

Introduction A growing number of adult patients are seeking orthodontic treatment. This research aimed to analyze the particulars of patients seeking retreatment and identify the causes of their original treatment failure. Methods An online questionnaire survey of adults seeking first-time orthodontic treatment (control) and retreatment (study) was conducted. Index of complexity, outcome, and need (ICON) scores were determined. Appraisal of treatment records was carried out to identify the causes of original treatment failure. Results No significant differences were found between retreatment adult patients and first-timers regarding reasons for seeking orthodontic treatment, malocclusion type, self-perception of malocclusion, level of self-motivation, willingness for surgery, expectations of treatment improvement and duration. The predominant reason for seeking treatment in both groups was for aesthetic concerns. Retreatment patients presented with lower ICON scores (39.4; standard error, 0.26) than the first-time patients (54.3; standard error, 0.23), P ≤0.001. The predominant reasons for original treatment failings were poor treatment, maturational changes, inadequate retention, shortcomings in diagnosis and treatment planning, and unfavorable growth. Other causes were related to transverse deficiency, secondary malocclusion (after periodontal breakdown), poor retention compliance, and temporomandibular joint degeneration. Conclusions Adult orthodontic retreatment and first-time seekers' profiles are remarkably similar. Aesthetic concerns were the leading reasons patients sought treatment. ICON was not a useful proxy of patient profiles. Poor treatment was the chief reason for the failure of the original treatment. In terms of clinical significance, clinicians should be mindful of the patient profiles of retreatment seekers and vigilant about the possible causes of failings of orthodontic treatment to avoid suboptimal outcomes.

Given that a properly formed utilitarian response to healthcare distribution issues should evaluate cost effectiveness against the total utility increase, it follows that any utilitarian cost-effectiveness metric should be sensitive to increases in both individual and social utility afforded by a given intervention. Quality adjusted life year (QALY) based decisionmaking in healthcare cannot track increases in social utility, and as a result, the QALY cannot be considered a strict utilitarian response to issues of healthcare distribution. This article considers arguments against, and a possible defence of, the QALY as a utilitarian concept; in response, the article offers a similar — but properly formed — utilitarian metric called the (IALY). This article also advances a tool called the ‘glee factor’ (GF) on which the IALY may lean in a similar way to which the QALY leans on the Rosser Index.

ObjectiveToe systolic pressure is a component of the standard vascular and diabetic foot assessment. Until now, clinicians have measured only first toe pressure given a lack of evidence for measurements of the other toes. In diabetic patients, first toe measurements are often not possible because of ulceration or amputation. It was hypothesized that the adjacent second toe systolic pressure measurements would be interchangeable with those of the first toe.MethodsA prospective study was performed on 100 participants with diabetes mellitus. Duplicate systolic toe pressures were measured in the first toe and adjacent second toe using the Systoe Automated Toe Pressure System, Systoe Photophlethysmograph Sensor Cuff, and occlusion cuffs measuring 120 × 25 mm for the first toe and 90 × 15 mm for the second toe. Correlation analysis was followed by Ordinary Least Products regression to detect and distinguish fixed and proportional bias between the two toe measurements. The acceptable limits of interchangeable results were defined as 5–10 mmHg.ResultsCorrelation coefficient r = 0.908; p

Setting Contact tracing using pediatric index cases has not been adequately investigated in high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence settings. Objective To determine the yield of contact tracing in household contacts of pediatric TB index cases in Botswana. Design Index cases included all pediatric (age ≤ 13 years) TB admissions from January 2009 to December 2011 to Botswana's largest referral hospital. A contact tracing team identified cases, conducted home visits, symptom-screened contacts and referred those with ≥ 1 TB symptoms. The primary outcome was newly diagnosed TB in a contact. Results From 163 pediatric index cases, 548 contacts were screened (median 3 contacts/case, interquartile range [IQR] 2-4). Of these, 49 (9%) were referred for positive symptoms on screening and 27/49 (55%) were evaluated for active TB. Twelve new TB cases were diagnosed (12/548, 2.2%); the median age was 31 years (IQR 23-38); 11 (92%) were smear-positive. Ten (83%) had known HIV status: 7 (70%) were HIV-positive. To find one new TB case, the number needed to contact trace (index cases/new cases) was 13.6, and the number needed to screen (contacts/new cases) was 46. Conclusion This yield of contact tracing using pediatric index cases is similar to the traditional adult index case approach. Improving the proportion of symptomatic contacts evaluated may increase yield.

As the number of Australians engaging in short-term international travel increases, so does the opportunity for importing overseas-acquired infectious diseases. This study aimed to determine knowledge of infectious disease risks and pre-travel health advice (PTHA) seeking behaviour among Western Australians travelling to Bali, Indonesia or Thailand. Passengers departing from Perth International Airport were invited to participate in a self-administered survey. The survey determined PTHA seeking behaviour, knowledge of specific disease risks, and expected disease-prevention behaviours abroad. Multivariate regression modelling was used to assess demographic and travel-related factors associated with seeking PTHA. Responses from 1334 travellers were analysed. The proportion correctly identifying specific overseas disease risks ranged from 27% to 98%. High levels of planned disease-preventive behaviours were reported; however only 32% of respondents sought PTHA for their trip, most commonly from friends/family (15%) or a GP (14%). Many travellers (87%) made online travel purchases, but few (8%) used the Internet to source PTHA. WA travellers to Bali and Thailand were unlikely to seek PTHA and knowledge varied regarding infectious disease risks associated with travel. High rates of internet use when planning travel may provide an opportunity for destination-specific health promotion messaging and should be explored.

In his book Untersuchungen zur Neusumerischen Textilindustrie (UNT), Hartmut Waetzoldt 1 has written extensively on the interpretation of Ur III textile texts. His emphasis in that work was directed towards the difficult task of understanding the cryptic texts that served to log the administration of the work of the textile industry. The aim of this paper is to bring together the information from the administrative texts that describe the tasks of spinning and weaving wool and to interpret these in the practical terms of textile making in order to gain a better understanding of the nature of these textiles. This will use the knowledge base gained by the Danish National Research Foundation’s Centre for Textile Research in Copenhagen (CTR). In particular, it will use the results of spinning and weaving experiments that were designed by CTR. The interpretation of the texts used here will closely follow that given by Waetzoldt in UNT. 2 In a discussion on the manufacture of woolen textiles it is natural to start by considering wool quality before going on to consider the spinning of the yarn and the weaving of the textiles. The textile tablets list many different types of fabrics and garments. However, the intention here is to concentrate on four of the main types of textile, namely, tug guz-za, tug nig-lam, tug us-bar and tug bar-dul 5 (which, for convenience, will be written in this paper without the determinatives). It will be shown that the eventual type of fabric produced was determined by both the selection of the wool and the spinning of the yarn.

The process of switching on bistable spatial dissipative solitons in a VCSEL with frequency selective feedback is analyzed experimentally and theoretically. Two regimes of successful writing of spatial solitons with an external pulse are identified: for short durations of the writing beam pulse, the input amplitude has to increase, while for longer durations, the input amplitude can remain constant. Switch on spectrograms of the frequency spectrum show a transient dynamics over many modes of the external cavity with a drift of the central frequency from higher to lower frequency. Such a multi-mode regime is almost independent of the frequency of the writing beam. It is interpreted to be due to the existence of multiple unstable solitons with different frequencies which channel the transient dynamics. Good agreement between experimental results and numerical simulations in both the time and frequency domains is found.

Despite high cure rates 25% of children with acute lymphoblastic leukaemia (ALL) relapse and have dismal outcome. Crucially, many are currently stratified as standard risk (SR) and additional markers to improve patient stratification are required. Here we have used diagnostic bone marrow specimens from 101 children with pre-B ALL to examine the use of gene expression profiles (GEP) as predictors of long-term clinical outcome. Patients were divided into two cohorts for model development and validation based on availability of specimen material. Initially, GEP from 55 patients with sufficient material were analysed using HG-U133A microarrays, identifying an 18-gene classifier (GC) that was more predictive of outcome than conventional prognostic parameters. After feature selection and validation of expression levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR), a three-gene qRT-PCR risk index [glutamine synthetase (GLUL), ornithine decarboxylase antizyme inhibitor (AZIN), immunoglobulin J chain (IGJ)] was developed that predicted outcome with an accuracy of 89% in the array cohort and 87% in the independent validation cohort. The data demonstrate the feasibility of using GEP to improve risk stratification in childhood ALL. This is particularly important for the identification of patients destined to relapse despite their current stratification as SR, as more intensive front-line treatment options for these individuals are already available.

In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53–442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 >8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

A relationship between maternal and child use of general practitioners (GPs) has been shown to exist for some time, however, the reasons for this relationship are not clear and the extent to which this relationship extends to tertiary care is unknown. The aim of this study was to examine the relationships between the utilisation of health care by siblings and mothers over a 14 year period. A retrospective cohort study of 756 mothers and their 1494 children up to age 14 years was conducted in three general practices in Western Australia. Medicare claims and hospital morbidity records for 1984-1997 were linked using deterministic and probabilistic matching. Generalised Estimating Equations and correlations were used to examine the relationships between the utilisation of primary and hospital health care by family members. Significant correlations were found between hospital admissions of all participants and their GP visits, specialist visits, pathology and diagnostic imaging combined and hospital length of stay. There was a strong association between siblings' use of GPs. A child's rate of GP attendance increased with that of its mother. There was a weak but significant relationship between siblings' use of hospitals, and a child's hospital admission rate increased with that of its mother. It is concluded that there is a strong relationship between siblings' use of GPs and a weaker but still significant association between the hospital admissions of siblings. As expected, there were strong associations between mother and child visits to GPs. There was also an association between a mother's use of hospital and that of her children. This finding reduces the plausibility that the relationships found between utilisation of health care by siblings and mothers can be explained entirely by behavioural factors, and suggests the presence of intergenerational correlation of morbidity. © 2005 Elsevier Ltd. All rights reserved.

6 pages, 10 figures.-- PACS nrs.: 42.65.Sf; 05.65.+b; 45.70.Qj., The universality of two mechanisms of motion of patterns in nonlinear optics is demonstrated. In the first one, two-dimensional disordered patterns are shown to scroll with constant velocity after transients are discarded. In the second case, pattern motion is induced by background modulations. Spatially periodic patterns lock to maxima or minima of the underlying modulation depending on its wavevector., We acknowledge support from the European projects QUANTIM and FunFACS and from EPSRC. AJS and GLO acknowledge support from SGI. GLO thanks the Royal Society–Leverhulme Trust and Centro Studi Dinamiche Complesse, University of Florence, Sesto Fiorentino, Italy.

Children as young as 6 years old can perform spirometry, yet the relationship between current asthma, lung function, and bronchial responsiveness has not been described at this age; 2,537 children from a community-based birth cohort were assessed at 6 years of age, with history (n = 2,141), physical examination (n = 1,995), standard spirometry (n = 1,735), and a random sample (n = 711) offered methacholine challenge. Males had greater values of FVC and FEV(1) but not of mean forced expiratory flow during the middle half of the FVC or FEV(1)/FVC than females. The greatest influences on lung function at 6 years were height, sex, birth weight, and wheezing in the first year of life. Children with current asthma had small but significant deficits in lung function and were more sensitive to methacholine. The optimal cutpoint for determining heightened bronchial responsiveness was found to be a 15% fall in FEV(1) at a dose of 1.8 mg/ml. A negative test could be useful in excluding a diagnosis of asthma (negative predictive value of 92%). Lung function testing, including methacholine challenge, is feasible in 5- to 7-year-old children and has the potential to contribute to the clinical management of children with asthma.

Trust is an essential part of health care-not only between clinicians and patients but also between staff and management. Research shows us that trust has a beneficial impact on many aspects of working life, including job satisfaction and organisational effectiveness, and both these factors have been shown to affect the quality of patient care. In addition, trust will now be the keystone for any system developed for services to learn from untoward incidents, such as the Reporting and Learning System of the National Patient Safety Agency in the UK. This type of trust is complex and is explored in terms of what staff need from management and the potential conflicts that might be involved in developing trust in a healthcare organisation. This paper looks at the societal and emotional context of health care today and at research from other organisations which shows the factors that must be in place to establish trust. It reviews the attributes of leaders who are seen as trustworthy, and looks at how all this can be used to increase the reporting of and learning from error.

Doctors have long been considered at risk of occupational stress.A postal survey of all members of the Intensive Care Society using validated instruments.Eight-five per cent of members returned questionnaires and 70% were eligible for the study. Twenty-nine per cent were suffering General Health Questionnaire-12 (GHQ-12) identified distress and 12% Symptom Checklist-Depression (SCL-D) defined depression. There were no significant age or sex differences between staff suffering distress or depression and those who did not. Dissatisfaction with career correlated highly with both distress and depression (P0.01). Twenty doctors (3%) were bothered by suicidal thoughts. The most stressful aspects of work were bed allocation, being over-stretched, effect of hours of work and stress on personal/family life, and compromising standards when resources are short. Logistic regression revealed mental health problems were predicted by five stressors: 'lack of recognition of one's own contribution by others'; 'too much responsibility at times'; 'effect of stress on personal/family life'; 'keeping up to date with knowledge'; and 'making the right decision alone'.Nearly one in three ICU doctors appeared distressed (GHQ), and one in 10 depressed (SCL-D); this is no greater than that reported in other specialities. Perceived stressors reveal some key areas of concern for the employer and the specialty.

The rapidly developing field of optomechanics aims at the com- bined control of optical and mechanical modes1–3. In cold atoms, the spontaneous emergence of spatial structures due to opto- mechanical back-action has been observed in one dimension in optical cavities3–8 or highly anisotropic samples9. Extensions to higher dimensions that aim to exploit multimode configurations have been suggested theoretically10–16. Here, we describe a simple experiment with many spatial degrees of freedom, in which two continuous symmetries—rotation and translation in the plane orthogonal to a pump beam axis—are spontaneously broken. We observe the simultaneous long- range spatial structuring (with hexagonal symmetry) of the density of a cold atomic cloud and of the pump optical field, with adjustable length scale. Being based on coherent phenom- ena (diffraction and the dipole force), this scheme can poten- tially be extended to quantum degenerate gases.

Packets of light persisting in a continuously driven nonlinear resonator in the time domain offer new possibilities not only for applications in all-optical storage, pulse reshaping and wavelength conversion, but also for fundamental experiments in nonlinear science.

As part of an investigation of the biochemical interactions between the salmon louse Lepeophtheirus salmonis and Atlantic salmon Salmo salar, we characterized protease activity in the skin mucus of noninfected Atlantic salmon and Atlantic salmon infected with L. salmonis and in an L. salmonis whole-body homogenate. Zymography revealed that mucus from infected salmon contained a series of low-molecular-mass (17-22 kDa) serine proteases that were not present in the mucus of noninfected salmon. Based on molecular mass, inhibition studies, and affinity chromatography, the series of proteases was identified as being trypsin-like. Similar proteases were observed in the L. salmonis homogenate and in mucus from noninfected Atlantic salmon following a 1-hr incubation with live L. salmonis. An antibody raised against Atlantic salmon trypsin failed to recognize any proteases in the mucus of noninfected salmon or infected salmon or in the L. salmonis homogenate. Collectively, these findings suggest that the trypsin-like proteases present in the mucus of infected Atlantic salmon were produced by L. salmonis, possibly to aid in feeding and evasion of host immune responses.

Pancreatic elastase-1 (EL-1) is a specific human protease synthesised by the acinar cells. It is stable, unaffected by exogenous pancreatic enzyme treatment, and correlates well with stimulated pancreatic function tests. We report our experience of EL-1 measurements in 142 patients from a large cystic fibrosis (CF) clinic. The median patient age was 7.7 years (range, 0.1-20.8 years), 93 were homozygous and 38 heterozygous for DeltaF508, and 11 had other or unidentified mutations. There were 85 non-CF control subjects. Seven were pancreatic sufficient (PS). The median (quartile 1-quartile 3) fecal EL-1 of the 135 pancreatic insufficient (PI) patients was 10 microg/g stool (2.5-33); of the 7 PS patients, 698 microg/g stool (400.5-824.5), and of the non-CF controls, 615 microg/g stool (420-773). Using the Mann-Whitney U test, there was a statistically significant difference for fecal EL-1 activity between the PS and PI patients (P = 0.0001) and the PI and control group (P < 0.0001), but not between the control and PS groups (P = 0.63). Median (quartile 1-quartile 3) fecal EL-1 in the pancreatic insufficient DeltaF508 homozygotes was 10 microg/g stool (2-33), and in the heterozygotes 12 microg/g stool (4-39) (not significant, P = 0.62). We now use fecal EL-1 as evidence of PI in screened CF infants (reliable over the age of 2 weeks); in older CF patients at diagnosis; for confirming the need for pancreatic enzymes in patients referred to the clinic already taking enzymes; for annual monitoring of PS patients to detect the onset of PI; and as supporting evidence when excluding the diagnosis of CF in patients attending the pediatric gastroenterology clinic. The low values in the first 2 weeks in some normal and premature infants, and the persisting normal values in PS infants, make the fecal EL-1 test unsuitable for neonatal CF screening.

We show theoretically that patterns with concentric rings of bright or dark spots made up by modes with coprime azimuthal indexes may arise in codimension one bifurcations in optical systems with a metallic diffractor, a polarizer, and a nonlinear medium. These patterns are a consequence of diffraction-induced polarization in systems without polarization dynamics. As an example of this type of system, we investigate numerically the symmetry-breaking bifurcations of a ring laser with a metallic duct and a polarizer inside the optical cavity.

The National Clinical Assessment Service (NCAS), an NHS organisation that assesses doctors and dentists referred to them because of perceived difficulties, has produced a report describing data arising from its first 4 years, showing that male doctors were referred to the service considerably more often than female doctors. Despite women accounting for 42% of the general practitioner medical workforce and 37% of the medical hospital and community (H&C) workforce in 2004, only 13% of GPs and 20% of H&C NCAS referrals were women. When the H&C data were split into specialties, women were under-represented proportionally in all specialties. This paper offers a review of possible reasons for these gender differences and in doing so contributes to the debates concerning problems in performance and also the costs of employing a growing proportion of women doctors. Firstly, it hypothesises that the NCAS data may be non-representative of similar agency data, but finds that in disciplinary organisations of various types around the world, men are consistently over-represented. Secondly, it suggests that perhaps men are referred to such agencies more often than women because their employers are more lenient on women. There is no evidence for this, and it requires primary research to investigate it further. Finally, it considers gender differences in the attributes, beyond technical skills, that underpin a good doctor–patient relationship and finds that, on these attributes, women usually excel over men. In addition, far fewer women are disciplined for addiction. The implications of this for education and rehabilitation are considered. It concludes that any analysis of the economic costs of employing a greater proportion of female doctors must take into account the higher costs of men's litigation, discipline and retraining.

Involving citizens in public decision-making has become increasingly important over the last three decades. Distrust of government, academia, and big business; citizen activism; changing values and legislative requirements have converged to feed a growing demand from citizens to be involved. A dilemma arises when public managers try to communicate project plans with citizens using ‘rational’ models of problem-solving, where citizens express reactions to projects as judgments based on individual values. The fit of a project with one's values is the basis of most individual decision-making, and is at the heart of citizens' choice to become involved. Solving this dilemma involves moving outside limited rational models and entering the messy world of values.

The basic physics of nonlinear optics in semiconductors is reviewed. Optical bistability due to increasing absorption and in a Kerr cavity is discussed, as are spatial solitons in a Kerr medium. These introduce recent research on spontaneous pattern formation and soliton-like structures in semiconductor cavity models. Applications to optical information processing are discussed, and simulations of a soliton array memory presented.

We show numerically that modulational instability of two-dimensional solitary waves in quadratic media leads to the formation of a train of quasi-stable three-dimensional light bullets of mutually trapped fundamental and second harmonic pulses. The dynamics and stability of these bullets are studied both numerically and variationally. Small deviations from the stationary bullet profile generally lead to long lived pulsations. Regions of unstable behaviour (decay) are found for both positive and negative mismatches.

We show that the transverse field in a laser with intra-cavity Kerr lens may be approximated by a spatial soliton, and so the laser can be thought of as a “spatial soliton laser”. Using a simple perturbation approach based on the nonlinear Schrodinger equation (NLS) we find analytical solutions which are in good agreement with numerical results from our master equation. This agreement is improved when we combine the soliton solution with a Gaussian dependent on the position of the Kerr lens. We discuss the limitations to the soliton perturbation theory. With appropriate placement, either a positive or a negative Kerr lens can induce spatial soliton laser action.

Summary form only given. Spontaneous optical pattern formation occurs in a variety of nonlinear systems [1], including hot atomic vapors [2]. On the other hand, the spatial self-organization of atomic ensembles due to opto-mechanical coupling has received a lot of interest in recent years [3].We report on the observation of transverse self-organization of a cold atomic cloud (issued from a magnetooptical trap) under the action of a single pump laser beam. Two symmetries (translation and rotation) in the plane orthogonal to the beam propagation direction are spontaneously broken. We use a simple optical feedback scheme [4], where the transmitted pump beam is retro-reflected to the atoms by a high-reflectivity mirror located at a distance d behind the cloud. This feedback loop transforms phase fluctuations of the transmitted wave into intensity fluctuations, which then react on the atomic medium. If the feedback is positive, a transverse instability can develop leading to the spontaneous apparition of patterns in the transmitted pump intensity profile, as shown in the figure below (left).Using a weak probe beam sent a few tens of μs after the e,tinction of the pump, we demonstrate that the instability also results in a transverse spatial ordering of the atomic medium as shown in the right image. The cold atoms thus e,perience strong spatial bunching due to the dipole force associated to the inhomogeneous intensity distribution. We identified two different instability regimes. For short pump durations (- 1 μs), high pump intensity and cloud optical density, the instability relies on the Kerr effect (electronic nonlinearity). For longer pump durations (- 100 μs), the instability is driven by the opto-mechanical effect, resulting in lower intensity and optical density thresholds than for the electronic nonlinearity. These observations are well reproduced by a theoretical model including the coupled dynamics of the light field and the atomic e,ternal degrees of freedom.

A saturable absorber in a cavity is shown to sustain stable bleached areas which can be created by applying a short, localized address pulses (optical bullets). These bullet-holes can be controlled and configured as a "spatial soliton" memory array. The existence and stability of these states is investigated by taking advantage of their cylindrical symmetry, and similar methods show that the Kerr cavity can also support stable localized states.

Patients relapsing with T-cell acute lymphoblastic leukemia (T-ALL) face a dismal outcome. The aim of this study was to identify new markers of drug resistance and clinical response in T-ALL. We measured gene expression and drug sensitivity in 15 pediatric T-ALL cell lines to find signatures predictive of resistance to 10 agents used in therapy. These were used to generate a model for outcome prediction in patient cohorts using microarray data from diagnosis specimens. In three independent T-ALL cohorts, the 10-drug model was able to accurately identify patient outcome, indicating that the in vitro–derived drug–gene profiles were clinically relevant. Importantly, predictions of outcome within each cohort were linked to distinct drugs, suggesting that different mechanisms contribute to relapse. Sulfite oxidase (SUOX) expression and the drug-transporter ABCC1 (MRP1) were linked to thiopurine sensitivity, suggesting novel pathways for targeting resistance. This study advances our understanding of drug resistance in T-ALL and provides new markers for patient stratification. The results suggest potential benefit from the earlier use of 6-mercaptopurine in T-ALL therapy or the development of adjuvants that may sensitize blasts to this drug. The methodology developed in this study could be applied to other cancers to achieve patient stratification at the time of diagnosis. Cancer Res; 73(9); 2749–59. ©2013 AACR.

Background Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms. Results Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (IL-7R), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort. Conclusions We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.

The dynamics of a broad-area vertical-cavity surface-emitting laser (VCSEL) with frequency-selective feedback supporting bistable spatial solitons is analyzed experimentally and theoretically. The transient dynamics of a switch-on of a soliton induced by an external optical pulse shows strong self-pulsing at the external-cavity round-trip time with at least ten modes excited. The numerical analysis indicates an even broader bandwidth and a transient sweep of the center frequency. It is argued that mode-locking of spatial solitons is an interesting and viable way to achieve three-dimensional, spatio-temporal self-localization and that the transients observed are preliminary indications of a transient cavity light bullet in the dynamics, though on a non negligible background.

We report on the existence, stability and dynamical properties of two-dimensional self-localized vortices with azimuthal numbers up to 4 in a simple model for lasers with frequency-selective feedback. We build the full bifurcation diagram for vortex solutions and characterize the different dynamical regimes. The mathematical model used, which consists of a laser rate equation coupled to a linear equation for the feedback field, can describe the spatiotemporal dynamics of broad area vertical cavity surface emitting lasers with external frequency selective feedback in the limit of zero delay., P.V.P., D.G. and P.C. acknowledge financial support from MEC (Spain), FEDER (EU) through Grants No. FIS2007-60327 FISICOS and No. TEC2006-10009 PhoDeCC, N. N. R. acknowledges financial support from RFBR (Russia) grant 09-02-90472-Ukr-f-a.

We present numerical simulations and analysis of optical vortex propagation in a 3D self-defocussing medium. On plane wave background initial conditions composed of points and lines of phase discontinuity are shown, in some cases, to evolve towards a regular crystal of fully nonlinear vortices. In other cases the solution more resembles a vortex gas. For gaussian beams, we have derived a simple set of ordinary differential equations which are shown to accurately describe the motion of a single vortex while the background beam undergoes significant spreading.

A numerical study of continuous-wave and pulse propagation in three-core fibre nonlinear directional couplers is presented. Intensity dependent demultiplexing is illustrated; in particular, novel nonlinear behaviour where a very small change in peak input intensity alters the core from which a pulse emerges.

It is a common perception that coronary heart disease (CHD) deaths will decline by 2% for every 1% decrease in serum total cholesterol (TC). We investigated the changes in serum TC concentrations obtained with simvastatin, an inhibitor of hydroxymethylglutaryl-CoA reductase, in 70 hypercholesterolemic subjects. Although simvastatin reduced serum TC concentrations by 30% after 6 months, calculations from age- and risk-related TC quintiles show that the absolute difference in attributable CHD deaths would be just > 1%. These results are reminiscent of the experience from several large prospective primary drug trials that demonstrated impressive relative benefit ratios but much smaller absolute differences (< 2%) in CHD endpoints between the treated and untreated groups. This epidemiologically based approach of assessing efficacy and potential long-term benefit of a lipid-lowering drug may be more appropriate and potentially less misleading than just the percentage change of TC (or other lipoproteins) so frequently reported in short-term drug trials.

We study analytically and numerically a very simple nonlinear optical system, a thin slice of Kerr material with a single feedback mirror. Theoretical analysis shows that for both a focusing and defocusing medium the plane-wave solution is unstable above a certain input intensity and a hexagonal pattern of bright spots should form. The amplitude equations for this system are three coupled Ginzburg-Landau type equations. Numerical analysis confirms these results; moreover by further increasing the input intensity, the hexagonal solution becomes itself unstable and turbulent motion sets in.

We present a general form of master equation for nonlinear-optical cavities that can be described by an ABCD matrix. It includes as special cases some previous models of spatiotemporal effects in lasers.

Pulse generation in a two-photon laser is investigated theoretically. A simple model including dispersion, linear absorption, and two-photon saturable gain yields stable mode-locked pulses with a sech2 intensity profile. Unlike as with self-phase-modulation methods, the pulse width is independent of the nonlinear parameters.

Continuous-wave and oscillatory transverse instabilities are predicted for counterpropagating waves in Kerr media for both focusing and defocusing nonlinearities. Neither a cavity nor a finite response time is required. Computed Gaussian-beam results agree well with analytic plane-wave calculations that straddle Raman-Nath and Bragg regimes.

Studies of the angular dependence of cw degenerate four-wave mixing in n-type InSb have yielded a value for the diffusion length, l(D), of 60 +/- 2 microm. From this, the dependence of l(D) on photoexcited carrier concentration is calculated. A simple model has been developed to estimate the corresponding parallel-processing capabilities of semi-conductor-based, all-optical, parallel-processing digital computing systems.

8 pages, 12 figures.-- PACS number(s): 42.65.Tg, 42.81.Dp.-- ArXiv pre-print: http://arxiv.org/abs/0908.3966, In this paper we study the formation and dynamics of self-propelled cavity solitons (CSs)in a model for vertical-cavity surface-emitting lasers (VCSELs)subjected to external frequency-selective feedback and build their bifurcation diagram for the case where carrier dynamics is eliminated. For low pump currents, we find that they emerge from the modulational instability point of the trivial solution, where traveling waves with a critical wave number are formed. For large currents, the branch of self-propelled solitons merges with the branch of resting solitons via a pitchfork bifurcation. We also show that a feedback phase variation of +/-(pi) can transform a CS (whether resting or moving) into a different one associated to an adjacent longitudinal external cavity mode. Finally, we investigate the influence of the carrier dynamics, relevant for VCSELs. We find and analyze qualitative changes in the stability properties of resting CSs when increasing the carrier relaxation time. In addition to a drifting instability of resting CSs, a distinctive kind of instability appears for certain ranges of carrier lifetime, leading to a swinging motion of the CS center position. Furthermore, for carrier relaxation times typical of VCSELs the system can display multistability of CSs., We acknowledge financial support from MICINN(Spain) and FEDER (EU) through Grants No. FIS2007-60327 FISICOS and No. TEC2006-10009 PhoDeCC.

We present a coupled-cavity model of a laser with frequency-selective feedback, and use it to analyze and explain the existence of stationary and dynamic spatial solitons in the device. Particular features of soliton addressing in this system are discussed. We demonstrate the advantages of our model with respect to the common Lang-Kobayashi approximation.