Athermal operation of multi-section slotted tunable lasers.

Two distinct athermal bias current procedures based on thermal tuning are demonstrated for a low-cost, monotlithic, three section slotted single mode laser, achieving mode-hop free wavelength stability of ± 0.04 nm / 5 GHz over a temperature range of 8-47 °C. This is the first time that athermal performance has been demonstrated for a three-section slotted laser with simple fabrication, and is well within the 50 GHz grid spacing specified for DWDM systems. This performance is similar to experiments on more complex DS-DBR lasers, indicating that strong athermal performance can be achieved using our lower-cost three section devices. An analytical model and thermoreflectance measurements provide further insight into the operation of multi-section lasers and lay the foundation for an accurate predictive tool for optimising such devices for athermal operation.

Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.

Effect of severe hypoalbuminemia on toxicity of high-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis.

High-dose melphalan with stem cell transplantation (HDM/SCT) extends survival and induces hematologic and clinical responses in patients with light chain (AL) amyloidosis. Eighty percent of melphalan is bound to plasma proteins (60% albumin-bound). We hypothesized that patients with profound hypoalbuminemia have a greater free melphalan fraction and more toxicity. Patients with AL amyloidosis treated with HDM/SCT between 2011 and 2014 with severe hypoalbuminemia (SH), defined as serum albumin ⩽2 g/dL were studied retrospectively. Sixteen patients with SH were identified. Forty-one patients without severe hypoalbuminemia (WSH) treated between 2011 and 2012 served as control. The incidence of acute renal failure requiring hemodialysis was 25% among patients with SH, compared with 5% among patients WSH (P=0.05). Not all patients who needed dialysis required it long term; 6.25% for SH and 2.44% for WSH (P=0.49). The rates of grade 3 or 4 febrile neutropenia and gastrointestinal toxicities were not significantly different between the groups. Engraftment kinetics were similar for both groups. Grade 4 renal toxicity and grade 3 lightheadedness were more frequent in patients with SH undergoing HDM/SCT for AL amyloidosis. Further studies into the mechanism of increased renal toxicity in patients with SH are warranted.

Balancing selection on MHC class I in wild brown trout Salmo trutta.

Evidence is reported for balancing selection acting on variation at major histocompatibility complex (MHC) in wild populations of brown trout Salmo trutta. First, variation at an MHC class I (satr-uba)-linked microsatellite locus (mhc1) is retained in small S. trutta populations isolated above waterfalls although variation is lost at neutral microsatellite markers. Second, populations across several catchments are less differentiated at mhc1 than at neutral markers, as predicted by theory. The population structure of these fish was also elucidated.

A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk.

BACKGROUND: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown. METHODS: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro. RESULTS: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35. CONCLUSION: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.

Prevalence, incidence and risk factors of epilepsy in older children in rural Kenya.

BACKGROUND: There is little data on the burden or causes of epilepsy in developing countries, particularly in children living in sub-Saharan Africa. METHODS: We conducted two surveys to estimate the prevalence, incidence and risk factors of epilepsy in children in a rural district of Kenya. All children born between 1991 and 1995 were screened with a questionnaire in 2001 and 2003, and those with a positive response were then assessed for epilepsy by a clinician. Active epilepsy was defined as two or more unprovoked seizures with one in the last year. RESULTS: In the first survey 10,218 children were identified from a census, of whom 110 had epilepsy. The adjusted prevalence estimates of lifetime and active epilepsy were 41/1000 (95% CI: 31-51) and 11/1000 (95% CI: 5-15), respectively. Overall two-thirds of children had either generalized tonic-clonic and/or secondary generalized seizures. A positive history of febrile seizures (OR=3.01; 95% CI: 1.50-6.01) and family history of epilepsy (OR=2.55; 95% CI: 1.19-5.46) were important risk factors for active epilepsy. After the second survey, 39 children from the same birth cohort with previously undiagnosed epilepsy were identified, thus the incidence rate of active epilepsy is 187 per 100,000 per year (95% CI: 133-256) in children aged 6-12 years. CONCLUSIONS: There is a considerable burden of epilepsy in older children living in this area of rural Kenya, with a family history of seizures and a history of febrile seizures identified as risk factors for developing epilepsy.

Computerized tomography scan of the brain in a community study of neurological impairment in Kenya.

Neurological impairment is common in resource-poor countries, but its causes are not clear. Computerized tomography (CT) of the brain has been used to determine the cause of brain insults that may manifest as neurological impairments. The authors conducted a community survey in Kilifi of 10 218 children aged 6 to 9 years to detect neurological impairment. From this survey, 34 children were identified, of whom 16 had motor deficits, 11 complex partial seizures, 4 microcephaly or macrocephaly, and 3 severe developmental delay. These children were assessed with elicitation of history, physical examination, and CT scan of the brain. Sixteen (47%) of the scans showed abnormalities: cerebral atrophy (n = 9), schizencephaly (n = 3), periventricular leukomalacia (n = 2), porencephalic cyst (n = 1), and agenesis of the corpus callosum (n = 1). The minimum prevalence of abnormalities on the CT scan of the brain is 1.56 of 1000, and the prevalence of schizencephaly is 0.29 of 1000. Motor impairments were more likely to show abnormality than the other indications. CT abnormalities are common in children with neurological impairment in Kenya, but the appearances did not identify a major cause.

Prevalence and risk factors of neurological disability and impairment in children living in rural Kenya.

BACKGROUND: There is little data on the burden of neurological impairment (NI) in developing countries, particularly in children of Africa. METHODS: We conducted a survey of NI in children aged 6-9 years in a rural district of Kenya. First, we screened for neurological disability by administering the Ten Questions Questionnaire (TQQ) to parents/guardians of children in a defined population. In phase two, we performed a comprehensive clinical and psychological assessment on children who tested positive on TQQ and on a similar number of children who tested negative. RESULTS: A total of 10 218 children were screened, of whom 955 (9.3%) were positive on TQQ. Of these, 810 (84.8%) were assessed, and of those who tested negative 766 (8.3%) were assessed. The prevalence for moderate/severe NI was 61/1000 [95% confidence interval (95% CI) 48-74]. The most common domains affected were epilepsy (41/1000), cognition (31/1000), and hearing (14/1000). Motor (5/1000) and vision (2/1000) impairments were less common. Of the neurologically impaired children (n = 251), 56 (22%) had more than one impairment. Neonatal insults were found to have a significant association with moderate/severe NI in both the univariate [odds ratio (OR) = 1.70; 95% CI 1.12-2.47] and multivariate analyses (OR = 1.30; 95% CI 1.09-1.65). CONCLUSIONS: There is a considerable burden of moderate/severe NI in this area of rural Kenya, with epilepsy, cognition, and hearing being the most common domains affected. Neonatal insults were identified as an important risk factor.

A mechanism of injury to the forefoot in car crashes.

OBJECTIVE: The purpose of this study was to determine a mechanism of injury of the forefoot due to impact loads and accelerations as noted in some frontal offset car crashes. METHODS: The impact tests conducted simulated knee-leg-foot entrapment, floor pan intrusions, whole-body deceleration, muscle tension, and foot/pedal interaction. Specimens were impacted at speeds of up to 16 m/s. To verify this injury mechanism research was conducted in an effort to produce Lisfranc type injuries and metatarsal fractures. A total of 54 lower legs of post-mortem human subjects were tested. Two possible mechanisms of injury were investigated. For the first mechanism the driver was assumed to be braking hard with the foot on the brake pedal and at 0 deg plantar flexion (Plantar Nominal Configuration) and the brake pedal was in contact with the foot behind the ball of the foot. The second mechanism was studied by having the ball of the foot either on the brake pedal or on the floorboard with the foot plantar-flexed 35 to 50 deg (Plantar Flexed Configuration). RESULTS: The Plantar Nominal injury mechanism yielded few injuries of the type the study set out to produce. Out of 13 specimens tested at speeds of 16 m/s, three had injuries of the metatarsal (MT) and tarsometatarsal joints. The Plantar Flexed Configuration injury mechanism yielded 65% injuries at high (12.5-16 m/s) and moderate (6-12 m/s) speeds. CONCLUSION: It is concluded that Lisfranc type foot injuries are the result of impacting the forefoot in the Plantar Flexed Configuration. The injuries were consistent with those reported by physicians treating accident victims and were verified by an orthopedic surgeon during post impact x-ray and autopsy. They included Lisfranc fractures, ligamentous disruptions, and metatarsal fractures.

Validity and reliability of the 'Ten Questions' questionnaire for detecting moderate to severe neurological impairment in children aged 6-9 years in rural Kenya.

BACKGROUND: The 'Ten Questions' Questionnaire (TQQ) is used to detect severe neurological impairment in children living in resource-poor countries. Its usefulness has been established in Asia and the Caribbean, but there are a few published studies from Africa. We evaluated the TQQ as part of a larger study of neurological impairment in a rural community, on the coast of Kenya. METHODS: The study was conducted in two phases from June 2001 to May 2002; in phase one, a community household screening of 10,218 children aged 6-9 years using the TQQ was performed. Phase two involved a comprehensive clinical and psychological assessment of all children testing positive on the TQQ (n = 810) and an equivalent number of those testing negative (n = 766). Data were interpreted using the impairment-specific approach. RESULTS: Overall, the sensitivity rates for screening the different impairments were: cognitive (70.0%), motor (71.4%), epilepsy (100%), hearing (87.4%) and visual (77.8%). All the specificity rates were greater than 96%. However, the positive predictive values were low, and ranged from 11 to 33%. CONCLUSIONS: These results are similar to those from other continents and provide evidence that the TQQ can be used to compare the epidemiology of moderate/severe impairment in different parts of the world. Furthermore, the TQQ can be used to screen for moderately/severely impaired children in resource-poor countries; however, the low positive predictive values mean that other assessments are required for confirmation.

Gene expression in the developing embryo and fetus.

Determining the stage- and tissue-specific patterns of gene expression shown by the embryo and fetus will provide information about the control of normal development. Identification of alterations in these patterns associated with specific abnormal phenotypes will also be informative regarding the underlying molecular mechanisms. In addition, qualitative and quantitative changes in gene expression that deviate from the norm may provide a potential marker system for predicting future developmental defects, a system that would be particularly useful in preimplantation embryo technologies before recipient transfer. However, there are a number of important issues regarding the interpretation and relevance of many gene expression studies currently undertaken that are often not considered or are ignored. Even when rigorous methodology is applied to detect differences in gene expression, their functional significance is rarely defined. This review discusses the relevance of gene expression changes as diagnostic markers in relation to protein and epigenetic changes and indicates that gene expression studies should be rigorously designed and interpreted to yield meaningful results.

Therapeutic kitchens for residents with dementia.

Long-term care facilities are increasingly incorporating some sort of kitchen, often referred to as a therapeutic kitchen, for resident, staff, and family use through remodeling efforts or new construction. A study, consisting of five site visits and a questionnaire mailed to 631 facilities providing dementia care, was conducted to identify physical features that are typically included in therapeutic kitchen design and to explore how these features support daily use in relation to activities programming and food service systems. Findings indicate that universal design features should be incorporated to a greater extent and certain features are more common, reinforce homelike imagery, or enhance safety. Results also suggest that a higher number of residents participate in more recreational activities, such as baking, than they do in household chores, such as meal set-up, and therapeutic kitchens are not always linked to food service systems.

An overview of AIDS dementia complex.

The major neurological complications associated with HIV infection include cognitive, behavioral, and motor disturbances, which may range in severity from subtle, mild cognitive deficits to the clinical syndrome referred to as HIV-associated dementia or AIDS dementia complex (ADC). As with Alzheimer's type dementia, caregivers for people with HIV/AIDS have the overwhelming and burdensome task of caring for someone with deteriorating cognitive abilities, increasing physical debilitation, and changes in personality. This article describes ADC as well as some of the similarities and differences from Alzheimer's type dementia, and offers some special considerations for older adults and HIV.

Ilioinguinal approach to manage benign pelvic and acetabular tumors.

Benign osteoblastic and cystic lesions involving the anterior column and wall of the pelvis and acetabulum are technically difficult areas to approach and achieve successful surgical outcomes. Tumors in this area are rare, leaving little information in the literature regarding how best to surgically approach them. Previous authors have reported small series of patients treated using anteromedial, iliofemoral, and intracapsular dissections. The ilioinguinal approach has been extensively described and used in the modern-day treatment of pelvic and acetabular fractures involving the anterior column and wall. Despite its use for acetabular trauma, application of the ilioinguinal approach in the treatment of benign pelvic and acetabular lesions has not been described. We reviewed the management of 5 patients with benign pelvic or acetabular tumors treated using the ilioinguinal approach. Diagnoses included aneurysmal bone cysts in 3 patients and osteoid osteomas in 2 patients, involving the pelvic anterior column and wall. The approach has permitted satisfactory exposure of the lesions for operative treatment. At an average follow-up of 3 years (range, 2-4 years), excellent functional outcome and no recurrences were noted. There were 2 patients with lateral femoral cutaneous nerve palsies, both of which resolved completely by 8 weeks. Encouraging results from our study demonstrate a new application for the ilioinguinal approach in the treatment of benign anterior column and wall lesions of the pelvis and acetabulum.

Loss of the maintenance methyltransferase, xDnmt1, induces apoptosis in Xenopus embryos.

DNA methylation is necessary for normal embryogenesis in animals. Here we show that loss of the maintenance methyltransferase, xDnmt1p, triggers an apoptotic response during Xenopus development, which accounts for the loss of specific cell populations in hypomethylated embryos. Hypomethylation-induced apoptosis is accompanied by a stabilization in xp53 protein levels after the mid-blastula transition. Ectopic expression of HPV-E6, which promotes xp53 degradation, prevents cell death, implying that the apoptotic signal is mediated by xp53. In addition, inhibition of caspase activation by overexpression of Bcl-2 results in the development of cellular masses that resemble embryonic blastomas. Embryonic tissue explant experiments suggest that hypomethylation alters the developmental potential of early embryo cells and that apoptosis is triggered by differentiation. Our results imply that loss of DNA methylation in differentiated somatic cells provides a signal via p53 that activates cell death pathways.

DNA methylation and control of gene expression in vertebrate development.

MeCpGs act as ligands for nuclear factors (repressors) that are components of chromatin modification and remodelling activities. The DNA-methylation-mediated repression system (Dnmt1s, MeCPs and MBDs) is highly conserved in vertebrates. DNA methylation is essential for normal vertebrate development. It is possible (but remains unproven) that the role of DNA methylation in regulating development is highly conserved in vertebrates. In mammals, DNA methylation has an additional role in regulating the expression of imprinted genes and in controlling X-inactivation.

Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos.

In Xenopus laevis zygotic transcription begins at the midblastula transition (MBT). Prior to this the genome is organized into chromatin that facilitates rapid cycles of DNA replication but not transcription. Here we demonstrate that DNA methylation contributes to the overall transcriptional silencing before MBT. Transient depletion of the maternal DNA methyltransferase (xDnmt1) by anti sense RNA during cleavage stages is associated with a decrease in the genomic 5-methyl-cytosine content and leads to the activation of zygotic transcription approximately two cell cycles earlier than normal. Hypomethylation allows the early expression of mesodermal marker genes such as Xbra, Cerberus, and Otx2, which are subsequently down-regulated during gastrulation of the xDnmt1-depleted embryos. The temporal switch in gene expression may account for the appearance of body plan defects that we observe. Loss of xDnmt1 can be rescued by the coinjection of mouse or human Dnmt1 protein. These results demonstrate that DNA methylation has a role in the regulation of immediately early genes in Xenopus at MBT.

Heelsticks in neonates for capillary blood sampling.

Capillary blood sampling via a heelstick is a common procedure performed on hospitalized neonates. If not performed properly, a heelstick can lead to complications. The clinical and financial impact of complications and redrawing of blood can be significant. Lancets/lancing devices are reviewed and proper procedure is discussed.

Management of frontal sinus fractures with posterior table involvement: a retrospective study.

Management of frontal sinus fracture has been a matter of debate. Combined fractures of the anterior and posterior walls have been managed by various techniques, including observation, open reduction and internal fixation, ablation, obliteration, and, most recently, cranialization. The earlier techniques have met with frequent complications, including sinusitis, mucopyocele, cerebrospinal fluid leak, meningitis, and brain abscess, along with various chronic pain symptoms. Cranialization of the frontal sinus was first introduced for injuries of both walls with intracranial penetration. From 1990 to 1996, frontal sinus fractures of 11 patients (10 men and 1 woman) were treated using the cranialization procedure. Based on patient history, clinical findings, radiographic diagnoses, operative techniques, and follow-ups of these patients the authors conclude that cranialization of the frontal sinus is a safe and effective method of treating posterior table frontal sinus fractures.