Dynamic wavelength control of laser pulse profiles at picosecond to nanosecond timescales.

We report on a novel combined laser pulse shaping and dynamic wavelength encoding capability based on a simple architecture implementing direct space to time mapping. There are several potential applications that can be enabled by the ability to control the instantaneous intensity or wavelength of an optical waveform on a picosecond-to-nanosecond timescale. To our knowledge, no known methods can access this temporal regime with a practical architecture. Here, we demonstrate an extension of the Space-Time Induced Linearly Encoded Transcription for Temporal Optimization (STILETTO) technique that can generate optical waveforms with a programmable instantaneous wavelength vs. time. We experimentally demonstrate the technique by generating self-gated spectrograms and show that it can encode dynamic wavelength vs time profiles at timescales not achievable by any other known method.

Programmable, direct space-to-time picosecond resolution pulse shaper with nanosecond record.

We demonstrate a novel, to the best of our knowledge, extension of optical arbitrary waveform generation capable of picosecond resolution over nanosecond duration. The method, called space-time induced linearly encoded transcription for temporal optimization, is based on direct space-to-time pulse shaping and is extended here to single-mode output with a programmable temporal profile. We develop the theory of operation and discuss ultimate limits on resolution, record length, and efficiency. We report on the results of an experimental demonstration showing ∼1ps resolution over 600 ps.

Offensive waste valorisation in the UK: Assessment of the potentials for absorbent hygiene product (AHP) recycling.

Offensive human waste refers to non-hazardous waste that contains body fluids from non-infectious humans, comprised of post-consumer Absorbent Hygiene Products (AHPs), swabs, dressings, bedding, gloves, and other materials. While this waste category requires more stringent handling, storage and disposal measures than general waste, its non-hazardous nature suggests that there are opportunities for waste valorisation. An inventory of 200 offensive human waste bags collected from various healthcare institutions in South-Eastern England show that about 76% of the waste is comprised of AHPs, most of which are adult incontinence pads and child nappies. Mixed plastics comprised of predominantly HDPE represent 9% of the waste. To evaluate the potentials for offensive human waste valorisation, small-scale separation tests involving artificially-soiled nappies and associated mixed plastic packaging wastes have been performed. Findings suggest that about 50% of the total superabsorbent polymer is recoverable from fluff pulp fractions, recoveries of which are unaffected by the presence of ionic species typically present in human waste. On the other hand, recovery of mixed plastic packaging is more challenging. Overall, however, findings suggest that viable AHP recycling is possible if recyclate materials are targeted towards non-food related markets outlets such as the construction and land remediation sectors.

Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders.

Despite the success of combination anti-retroviral therapy (cART), around 50% of HIV-infected individuals still display a variety of neuropathological and neurocognitive sequelae known as NeuroHIV. Current research suggests these effects are mediated by long-term changes in CNS function in response to chronic infection and inflammation, and not solely due to active viral replication. In the post-cART era, drug abuse is a major risk-factor for the development of NeuroHIV, and increases extracellular dopamine in the CNS. Our lab has previously shown that dopamine can increase HIV infection of primary human macrophages and increase the production of inflammatory cytokines, suggesting that elevated dopamine could enhance the development of HIV-associated neuropathology. However, the precise mechanism(s) by which elevated dopamine could exacerbate NeuroHIV, particularly in chronically-infected, virally suppressed individuals remain unclear. To determine the connection between dopaminergic alterations and HIV-associated neuroinflammation, we have examined the impact of dopamine exposure on macrophages from healthy and virally suppressed, chronically infected HIV patients. Our data show that dopamine treatment of human macrophages isolated from healthy and cART-treated donors promotes production of inflammatory mediators including IL-1ß, IL-6, IL-18, CCL2, CXCL8, CXCL9, and CXCL10. Furthermore, in healthy individuals, dopamine-mediated modulation of specific cytokines is correlated with macrophage expression of dopamine-receptor transcripts, particularly DRD5, the most highly-expressed dopamine-receptor subtype. Overall, these data will provide more understanding of the role of dopamine in the development of NeuroHIV, and may suggest new molecules or pathways that can be useful as therapeutic targets during HIV infection.

Single-shot optical recorder with sub-picosecond resolution and scalable record length on a semiconductor wafer.

We demonstrate a novel, single-shot recording technology for transient optical signals. A resolution of 0.4 ps over a record length of 54 ps was demonstrated. Here, a pump pulse crossing through a signal samples a diagonal "slice" of space-time, enabling a camera to record spatially the time content of the signal. Unlike related χ(2)-based cross-correlation techniques, here the signal is sampled through optically pumped carriers that modify the refractive index of a silicon wafer. Surrounding the wafer with birefringent retarders enables two time-staggered, orthogonally polarized signal copies to probe the wafer. Recombining the copies at a final crossed polarizer destructively interferes with them, except during the brief stagger window, where a differential phase shift is incurred. This enables the integrating response of the rapidly excited but persistent carriers to be optically differentiated. This sampling mechanism has several advantages that enable scaling to long record lengths, including making use of large, inexpensive semiconductor wafers, eliminating the need for phase matching, broad insensitivity to the spectral and angular properties of the pump, and overall hardware simplicity.

Early Mucosal Healing with Exclusive Enteral Nutrition is Associated with Improved Outcomes in Newly Diagnosed Children with Luminal Crohn's disease.

BACKGROUND: Exclusive Enteral Nutrition (EEN) induction in children with luminal Crohn's disease (CD) gives early mucosal healing (MH), but the long-term benefits of EEN-induced MH are just emerging. AIMS & METHODS: We prospectively followed an Australian cohort of newly diagnosed children with predominantly luminal CD who completed at least six weeks EEN and with paired clinical Pediatric Crohn's Disease Activity Index (PCDAI), biochemical (C-reactive protein; CRP) and endoscopic assessment at diagnosis and post EEN. All commenced immunomodulators (IMs) early (<3 months from diagnosis) and had a minimum of 1 year follow-up. Complete MH was a simple endoscopic score for Crohn's disease (SES-CD) of 0, and SES-CD≥1 was ascribed to active endoscopic disease (aED) and further divided into near complete MH (SES 1-3), mild active disease (SES-CD 4-10) and moderate to severe disease (SES-CD>10). The primary outcome was long-term supervised sustained remission (SR) on IMs alone without need for corticosteroids, infliximab (IFX) or surgery. RESULTS: A total of 54 eligible children (33 males) completing EEN induction were analysed. The median duration between pre and post EEN assessments was 60.5 days [interquartile range (IQR), 56-69.5]. Post EEN: clinical remission (PCDAI < 10) was observed in 45/54 (83%), and biochemical remission (PCDAI < 10 and CRP < 5 mg/dl) was observed in 39/54 (72%). Complete MH was observed in 18/54 (33%), near complete in 10/54(19%). SR was superior in those with complete MH vs. aED; 13/18, (72%) vs. 10/36 (28%), p = 0.003 at 1 year, 8/16, (50%) vs. 3/24, (8%), p = 0.008 at 2 years and (8/16, (50%) vs. 1/19, (6%), p = 0.005) at 3 years. Near-complete MH did not lead to superior SR. CONCLUSIONS: Only complete MH post EEN induction predicts more favourable SR for up to 3 years.

Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Diabetes is predictive of longer hospital stay and increased rate of complications in spinal surgery in the UK.

INTRODUCTION: Diabetes is a common co-morbidity of patients undergoing spinal surgery in the UK but there are no published studies from the UK, particularly with respect to length of hospital stay and complications. The aims of this study were to identify complications and length of hospital stay in patients with diabetes undergoing spinal surgery. METHODS: Data were collected retrospectively for 111 consecutive patients with diabetes (and 97 age and sex matched control patients, identified using computer records) who underwent spinal surgery between 2004 and 2010 in a single centre. The data collected included operative time, blood loss, details of surgery, Clavien complications and length of hospital stay. RESULTS: No significant differences were found by group in operative time, blood loss, instrumentation, use of graft or revision surgery. Overall complication rates were higher in the patients with diabetes than in the controls (28.8% vs 15.5%). The mean hospital stay was significantly longer for patients with diabetes than for control patients (4.6 vs 3.2 days, p<0.001). CONCLUSIONS: This study identified a significantly higher Clavien grade I complication rate and length of hospital stay in patients with diabetes undergoing spinal surgery than control patients (p=0.02). This has resulted in a predictive model being generated. Of note, no infections were seen in patients with diabetes, suggesting that infection rates in this particular group of patients undergoing spinal surgery might not be as high as considered previously.

Endogenous IL-21 regulates pathogenic mucosal CD4 T-cell responses during enhanced RSV disease in mice.

A role for interleukin-21 (IL-21) has recently been found in several diseases, but contribution to mucosal defences has not been described. In BALB/c mice infected with respiratory syncytial virus (RSV), IL-21 depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. This enhancement was accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to the lungs, with increased bronchoalveolar lavage interferon-γ and IL-17 levels. Adoptive transfer of splenic CD4 T cells from depleted mice into naive recipients replicated these effects, indicating that IL-21 mediates its effects via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on mucosal antiviral responses, assisting viral clearance, regulating pulmonary T- and B-cell responses, and inhibiting IL-17 production.

Quality of life in children with Crohn disease.

OBJECTIVES: : Quality of life (QOL) is reportedly poor in children with Crohn disease (CD) but improves with increasing disease duration. This article aims to detail QOL in a cohort of Australian children with CD in relation to disease duration, disease activity, and treatment. MATERIALS AND METHODS: : QOL, assessed using the IMPACT-III questionnaire, and disease activity measures, assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), were available in 41 children with CD. For this cohort, a total of 186 measurements of both parameters were available. RESULTS: : QOL was found to be significantly lower, and disease activity significantly higher (F = 31.1, P = 0.00), in patients within 6 months of their diagnosis compared with those up to 2.5 years, up to 5 years, and beyond 5 years since diagnosis. Higher disease activity was associated with poorer QOL (r = -0.51, P = 0.00). Total QOL was highest in children on nil medications and lowest in children on enteral nutrition. The PCDAI (t = -6.0, P = 0.00) was a significant predictor of QOL, with the clinical history (t = -6.9, P = 0.00) and examination (t = -2.9, P = 0.01) sections of the PCDAI significantly predicting QOL. Disease duration, age, or sex was neither related to nor significant predictors of QOL, but height z score and type of treatment approached significance. CONCLUSIONS: : Children with CD within 6 months of their diagnosis have impaired QOL compared with those diagnosed beyond 6 months. These patients, along with those with growth impairment, ongoing elevated disease activity with abdominal pain, diarrhoea and/or perirectal and extraintestinal complications, may benefit from regular assessments of QOL as part of their clinical treatment.

Periarticular calcification causing acute carpal tunnel syndrome: a case report.

We report a case of acute carpal tunnel syndrome caused by periarticular calcification (hydroxyapatite deposition disease) around the wrist joint in a 64-year-old woman. She had acute severe pain, exacerbated by wrist movements and extension of the fingers. Her full blood count, urea, electrolytes, uric acid, calcium, phosphate, alkaline phosphatase, and thyroid function levels were all within normal ranges, and her serum was negative for rheumatoid factor. Computed tomography revealed lobulated calcification close to the volar capsule. She underwent an emergency surgical decompression of the carpal tunnel under general anaesthesia within 3 hours of presentation. The flexor tendon sheaths were excised, and 'toothpaste-like' chalky material (hydroxyapatite crystals) in the capsule was removed. The pain was relieved dramatically and her median nerve function recovered. She was symptom-free at the one-year follow-up.

A novel size-selective airborne particle size fractionating instrument for health risk evaluation.

Health risks associated with the inhalation of airborne particles are known to be influenced by particle size. Studies have shown that certain nanoparticles, with diameters <100 nm, have increased toxicity relative to larger particles of the same substance. A reliable, size-resolving sampler able to collect a wide range of particle sizes, including particles with sizes in the nanometre range, would be beneficial in investigating health risks associated with the inhalation of airborne particles. A review of current aerosol samplers used for size-resolved collection of airborne particles highlighted a number of limitations. These could be overcome by combining an inertial deposition impactor with a diffusion collector in a single device. Verified theories of diffusion and inertial deposition suggested an optimal design and operational regime. The instrument was designed for analysing mass distribution functions. Calibration was carried out using a number of recognized techniques. The sampler was tested in the field by collecting size-resolved samples of lead containing aerosols present at workplaces in factories producing crystal glass. The mass deposited on each screen proved sufficient to be detected and measured by an appropriate analytical technique. Mass concentration distribution functions of lead were produced. The nanofraction of lead in air varied from 10 to 70% by weight of total lead.

Governance and the loss of biodiversity.

Most of the world's biodiversity occurs within developing countries that require donor support to build their conservation capacity. Unfortunately, some of these countries experience high levels of political corruption, which may limit the success of conservation projects by reducing effective funding levels and distorting priorities. We investigated whether changes in three well surveyed and widespread components of biodiversity were associated with national governance scores and other socio-economic measures. Here we show that governance scores were correlated with changes in total forest cover, but not with changes in natural forest cover. We found strong associations between governance scores and changes in the numbers of African elephants and black rhinoceroses, and these socio-economic factors explained observed patterns better than any others. Finally, we show that countries rich in species and identified as containing priority areas for conservation have lower governance scores than other nations. These results stress the need for conservationists to develop and implement policies that reduce the effects of political corruption and, in this regard, we question the universal applicability of an influential approach to conservation that seeks to ban international trade in endangered species.

Regulation of late flagellar gene transcription and cell division by flagellum assembly in Caulobacter crescentus.

Biogenesis of the single polar flagellum of Caulobacter crescentus is regulated by a complex interplay of cell cycle events and the progression of flagellum assembly. The expression of class III/IV flagellar genes requires the assembly of an early flagellar basal body structure, encoded by class II genes, and is activated by the transcription factor FlbD. Previous experiments indicated that the class II flagellar gene, flbE, encoded a trans-acting factor that was required for FlbD activity. Here, using mutant alleles of flbE we have determined that FlbE is either a structural component of the flagellum or is required for flagellar assembly and does not, as originally proposed, function as a trans-acting factor. We also demonstrate that two deleted derivatives of flbE have a dominant negative effect on the transcriptional activation of class III/IV flagellar genes that can be relieved by a gain-of-function mutation in flbD called bfa. This same mutation in flbD has been shown to restore class III/IV transcription in the absence of early class II flagellar assembly. These deleted mutants of flbE also exhibited a filamentous cell phenotype that was indistinguishable from that previously observed in class II flagellar mutants. Introduction of a flbD-bfa mutation into these cells expressing the deleted alleles of flbE, as well as several class II mutant strains, restored normal cell division and FtsZ localization. These results suggest that class III/IV transcription and a step in cell division are coupled to flagellar assembly by the same genetic pathway.

The Caulobacter crescentus flagellar gene, fliX, encodes a novel trans-acting factor that couples flagellar assembly to transcription.

The first flagellar assembly checkpoint of Caulobacter crescentus couples assembly of the early class II components of the basal body complex to the expression of class III and IV genes, which encode extracytoplasmic structures of the flagellum. The transcription of class III/IV flagellar genes is activated by the response regulator factor, FlbD. Gain of function mutations in flbD, termed bfa, can bypass the transcriptional requirement for the assembly of class II flagellar structures. Here we show that the class II flagellar gene fliX encodes a trans-acting factor that couples flagellar assembly to FlbD-dependent transcription. We show that the overexpression of fliX can suppress class III/IV gene expression in both wild-type and flbD-bfa cells. Introduction of a bfa allele of flbD into cells possessing a deletion in fliX restores motility indicating that FliX is not a structural component of the flagellum, but rather a trans-acting factor. Furthermore, extragenic motile suppressors which arise in DeltafliX cells map to the flbD locus. These results indicate that FlbD functions downstream of FliX in activating class III/IV transcription. beta-Lactamase fusions to FliX and analysis of cellular fractions demonstrate that FliX is a cytosolic protein that demonstrates some peripheral association with the cytoplasmic membrane. In addition, we have isolated a mutant allele of fliX that exhibits a bfa-like phenotype, restoring flbD-dependent class III/IV transcription in strains that contain mutations in class II flagellar structural genes. Taken together, these results indicated both a positive and negative regulatory function for FliX in coupling the assembly of class II basal body components to gene expression.

Injury prevention in Scotland--the case for a national strategy.

In children and young adults, injury overshadows other causes of death and is a major contributor to acute and long-term disability. Yet injury is more amenable to prevention than most other causes of ill health. The purpose of this paper is to present the case for the development and implementation of a national injury prevention strategy for Scotland. Systematic reviews of the evidence have identified a series of specific interventions that have been shown to reduce injury incidence, mortality or morbidity. Research suggests that over half of all traumatic deaths are avoidable in children. In addition to the responsibilities of individuals, parents, carers, schools and employers to prevent or to reduce the probability of injury, responsibility for injury prevention and the protection of the public from injury hazards lies with a range of national and local agencies in the UK. These vary across the country and are unco-ordinated. To reduce the number of deaths and disorders resulting from injury, and the costs associated with treating and caring for injured people and their families, we contend that the most pressing current need is to develop a national strategy for Scotland.

Functions of FKBP12 and mitochondrial cyclophilin active site residues in vitro and in vivo in Saccharomyces cerevisiae.

Cyclophilin and FK506 binding protein (FKBP) accelerate cis-trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal cellular functions of these proteins, however, are unknown. We altered the active sites of FKBP12 and mitochondrial cyclophilin from the yeast Saccharomyces cerevisiae by introducing mutations previously reported to inactivate these enzymes. Surprisingly, most of these mutant enzymes were biologically active in vivo. In accord with previous reports, all of the mutant enzymes had little or no detectable prolyl isomerase activity in the standard peptide substrate-chymotrypsin coupled in vitro assay. However, in a variation of this assay in which the protease is omitted, the mutant enzymes exhibited substantial levels of prolyl isomerase activity (5-20% of wild-type), revealing that these mutations confer sensitivity to protease digestion and that the classic in vitro assay for prolyl isomerase activity may be misleading. In addition, the mutant enzymes exhibited near wild-type activity with two protein substrates, dihydrofolate reductase and ribonuclease T1, whose folding is accelerated by prolyl isomerases. Thus, a number of cyclophilin and FKBP12 "active-site" mutants previously identified are largely active but protease sensitive, in accord with our findings that these mutants display wild-type functions in vivo. One mitochondrial cyclophilin mutant (R73A), and also the wild-type human FKBP12 enzyme, catalyze protein folding in vitro but lack biological activity in vivo in yeast. Our findings provide evidence that both prolyl isomerase activity and other structural features are linked to FKBP and cyclophilin in vivo functions and suggest caution in the use of these active-site mutations to study FKBP and cyclophilin functions.

Temperature-sensitive mutants of the EcoRI endonuclease.

The EcoRI endonuclease is an important recombinant DNA tool and a paradigm of sequence-specific DNA-protein interactions. We have isolated temperature-sensitive (TS) EcoRI endonuclease mutants (R56Q, G78D, P90S, V97I, R105K, M157I, C218Y, A235E, M255I, T261I and L263F) and characterized activity in vivo and in vitro. Although the majority were TS for function in vivo, all of the mutant enzymes were stably expressed and largely soluble at both 30 degrees C and 42 degrees C in vivo and none of the mutants was found to be TS in vitro. These findings suggest that these mutations may affect folding of the enzyme at elevated temperature in vivo. Both non-conservative and conservative substitutions occurred but were not correlated with severity of the mutation. Of the 12 residues identified, 11 are conserved between EcoRI and the isoschizomer RsrI (which shares 50% identity), a further indication that these residues are critical for EcoRI structure and function. Inspection of the 2.8 A resolution X-ray crystal structure of the wild-type EcoRI endonuclease-DNA complex revealed that: (1) the TS mutations cluster in one half of the globular enzyme; (2) several of the substituted residues interact with each other; (3) most mutations would be predicted to disrupt local structures; (4) two mutations may affect the dimer interface (G78D and A235E); (5) one mutation (P90S) occurred in a residue that is part of, or immediately adjacent to, the EcoRI active site and which is conserved in the distantly related EcoRV endonuclease. Finally, one class of mutants restricted phage in vivo and was active in vitro, whereas a second class did not restrict and was inactive in vitro. The two classes of mutants may differ in kinetic properties or cleavage mechanism. In summary, these mutations provide insights into EcoRI structure and function, and complement previous genetic, biochemical, and structural analyses.

Transpersonal processes: a bridge between object relations and attachment theory in normal and psychopathological development.

This paper has three aims: (a) to present the further development of the concept of transpersonal processes and the bimodal theory of relational cognition; (b) to show how the bimodal concept illuminates developmental theory and facilitates the move from object relations theory toward a relational systems model; and (c) to show how the attachment paradigm and the notions of internal working models (Bowlby, 1973) and self-reflective capacity (Fonagy, 1991) are both congruent and synergistic with the transpersonal and bimodal concepts.