Vegetative fragment production as a means of propagule dispersal for tropical seagrass meadows.

BACKGROUND AND AIMS: Long distance dispersal (LDD) contributes to the replenishment and recovery of tropical seagrass habitats exposed to disturbance, such as cyclones and infrastructure development. However, our current knowledge regarding the physical attributes of seagrass fragments that influence LDD predominantly stems from temperate species and regions. The goal of this paper is to measure seagrass fragment density and viability in two tropical species, assessing various factors influencing their distribution. METHODS: We measured the density and viability of floating seagrass fragments for two tropical seagrass species (Zostera muelleri and Halodule uninervis) in two coastal seagrass meadows in the central Great Barrier Reef World Heritage Area, Australia. We assessed the effect of wind speed, wind direction, seagrass growing/senescent season, seagrass meadow density, meadow location and dugong foraging intensity on fragment density. We also measured seagrass fragment structure and fragment viability; i.e., potential to establish into a new plant. KEY RESULTS: We found that seagrass meadow density, season, wind direction and wind speed influenced total fragment density, while season and wind speed influenced the density of viable fragments. Dugong foraging intensity did not influence fragment density. Our results indicate that wave action from winds combined with high seagrass meadow density increases seagrass fragment creation, and that more fragments are produced during the growing than the senescent season. Seagrass fragments classified as viable for Z. muelleri and H. uninervis had significantly more shoots and leaves than non-viable fragments. We collected 0.63 (±0.08 SE) floating viable fragments 100 m-2 in the growing season, and 0.13 (±0.03 SE) viable fragments 100 m-2 in the senescent season. Over a third (38%) of all fragments collected were viable. CONCLUSION: There is likely to be a large number of viable seagrass fragments available for long distance dispersal. This study's outputs can inform dispersal and connectivity models that are used to direct seagrass ecosystem management and conservation strategies.

Chirality of nanophotonic waveguide with embedded quantum emitter for unidirectional spin transfer.

Scalable quantum technologies may be achieved by faithful conversion between matter qubits and photonic qubits in integrated circuit geometries. Within this context, quantum dots possess well-defined spin states (matter qubits), which couple efficiently to photons. By embedding them in nanophotonic waveguides, they provide a promising platform for quantum technology implementations. In this paper, we demonstrate that the naturally occurring electromagnetic field chirality that arises in nanobeam waveguides leads to unidirectional photon emission from quantum dot spin states, with resultant in-plane transfer of matter-qubit information. The chiral behaviour occurs despite the non-chiral geometry and material of the waveguides. Using dot registration techniques, we achieve a quantum emitter deterministically positioned at a chiral point and realize spin-path conversion by design. We further show that the chiral phenomena are much more tolerant to dot position than in standard photonic crystal waveguides, exhibit spin-path readout up to 95±5% and have potential to serve as the basis of spin-logic and network implementations.

Guidelines for quantification of noise-induced hearing loss in a medicolegal context.

OBJECTIVES: Guidelines published in 2000 by the authors are widely used by medical and legal professionals in the UK for diagnosis of noise-induced hearing loss in a medicolegal context. However, they cannot be used for quantification of the noise-induced hearing loss, which is required in most cases. This requirement is addressed. DESIGN: A method is developed here to quantify noise-induced hearing loss, thereby overcoming this shortcoming. SETTING: Assessment of noise-induced hearing loss in medicolegal cases. PARTICIPANTS: A consecutive series of 124 cases of noise-induced hearing loss is used for evaluation. MAIN OUTCOME MEASURE: Magnitude of noise-induced hearing loss based on hearing threshold levels averaged over the frequencies 1, 2 and 3 kHz. RESULTS: The rationale of the method, practical application and three worked examples are developed. A simpler short-cut method is developed and shown to be equivalent to the full method in most cases. CONCLUSIONS: The method offers a practical approach to quantification of noise-induced hearing loss.

Waveguide-coupled photonic crystal cavity for quantum dot spin readout.

We present a waveguide-coupled photonic crystal H1 cavity structure in which the orthogonal dipole modes couple to spatially separated photonic crystal waveguides. Coupling of each cavity mode to its respective waveguide with equal efficiency is achieved by adjusting the position and orientation of the waveguides. The behavior of the optimized device is experimentally verified for where the cavity mode splitting is larger and smaller than the cavity mode linewidth. In both cases, coupled Q-factors up to 1600 and contrast ratios up to 10 are achieved. This design may allow for spin state readout of a self-assembled quantum dot positioned at the cavity center or function as an ultra-fast optical switch operating at the single photon level.

The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus.

AIMS: The prevalence of autoantibodies to zinc transporter 8 (ZnT8) in Czech children at the onset of Type 1 diabetes mellitus and dynamic changes in ZnT8 autoantibody levels during disease progression were studied. The value of ZnT8 autoantibody measurements in diagnosis of Type 1 diabetes was assessed. METHODS: Serum samples from 227 children with newly diagnosed Type 1 diabetes and from 101 control children without diabetes were analysed in a retrospective cross-sectional study. One hundred and seventy-one samples from 116 of the patients with diabetes were analysed in a follow-up study at (median) intervals of 1, 3, 5 and 10 years after onset of Type 1 diabetes. ZnT8 autoantibodies were measured using a bridging enzyme-linked immunosorbent assay, while antibodies to glutamic acid decarboxylase, insulinoma antigen 2 and insulin were measured by radioimmunoassays. RESULTS: ZnT8 autoantibodies were detected in 163/227 (72%) of children at Type 1 diabetes onset and in 1/101 (1%) of the control subjects. Sixteen out of 227 (7%) patients with Type 1 diabetes were antibody negative based on three antibodies (glutamic acid decarboxylase, insulinoma antigen 2 and insulin). This false-negative rate was reduced to 10/227 (4.4%) (P < 0.05) after inclusion of ZnT8 autoantibody measurements. Of the children, 142/227 (63%) were positive for at least three antibodies and the most common combination was insulinoma antigen 2, glutamic acid decarboxylase and ZnT8. ZnT8 autoantibody levels decreased over time after Type 1 diabetes onset and the presence and level of ZnT8 autoantibodies correlated with IA-2 autoantibodies. CONCLUSIONS: A ZnT8 autoantibody enzyme-linked immunosorbent assay showed 72% disease sensitivity and 99% specificity at Type 1 diabetes onset. Measurements of ZnT8 autoantibodies are important for Type 1 diabetes diagnosis and should be included in the panel of autoantibodies tested at the onset of Type 1 diabetes.

Guiding principles for the improved governance of port and shipping impacts in the Great Barrier Reef.

The Great Barrier Reef (GBR) region of Queensland, Australia, encompasses a complex and diverse array of tropical marine ecosystems of global significance. The region is also a World Heritage Area and largely within one of the world's best managed marine protected areas. However, a recent World Heritage Committee report drew attention to serious governance problems associated with the management of ports and shipping. We review the impacts of ports and shipping on biodiversity in the GBR, and propose a series of guiding principles to improve the current governance arrangements. Implementing these principles will increase the capacity of decision makers to minimize the impacts of ports and shipping on biodiversity, and will provide certainty and clarity to port operators and developers. A 'business as usual' approach could lead to the GBR's inclusion on the List of World Heritage in Danger in 2014.

Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung.

We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.

Asymmetric sensorineural hearing thresholds in the non-noise-exposed UK population: a retrospective analysis.

OBJECTIVES: To estimate the distribution of inter-aural sensorineural hearing threshold level differences in the non-noise-exposed adult population of the UK. SETTING: A two-stage population study carried out in 1979-1986, initially by postal questionnaire, followed up in a proportion of participants by clinical and audiological examination. PARTICIPANTS: Volunteers (n = 48 313) initially selected at random from the electoral registers of four cities, subsequently selected at random from questionnaire respondents stratified by answers to questions about hearing. MAIN OUTCOMES MEASURE: Inter-aural hearing threshold level differences measured audiometrically, as a function of age and gender. RESULTS: Tables of inter-aural threshold level differences provided as a resource with potential medicolegal, clinical and research applications. Based on the average of the frequencies 0.5, 1, 2 and 4 kHz, approximately 1% of the general UK population aged 18-80 years have an asymmetry of 15 dB or more. The prevalence is greater in older than in younger people. CONCLUSIONS: Inter-aural threshold differences greater than attributable to measurement error are not uncommon in the adult population, even after screening for conductive hearing loss and substantial noise exposure. They are typically of unknown origin.

SARS Surveillance Project--Internet-enabled multiregion surveillance for rapidly emerging disease.

INTRODUCTION: On March 15, 2003, CDC requested health-care and public health agencies to conduct surveillance for severe acute respiratory syndrome (SARS). The SARS Surveillance Project (SARS-SP) was established to rapidly implement multiregional SARS surveillance in emergency departments (EDs) by using existing Internet-based tools. OBJECTIVES: The objectives of SARS-SP were to 1) disseminate and update SARS screening forms for ED triage, 2) establish surveillance for SARS syndrome elements by using Regional Emergency Medicine Internet (REMI), 3) expand surveillance to multiple regions, and 4) evaluate the usefulness of Internet tools for agile surveillance during a rapidly emerging global epidemic. METHODS: SARS-SP developed, distributed, and updated an Internet-based triage form to identify patients for infection control and public health reporting. EDs then were invited to report visit frequencies with various SARS syndrome elements to local public health authorities by using the REMI Internet application (first in one metropolitan area, and later in four). After pilot-testing in one metropolitan area, the surveillance system was implemented in three others. RESULTS: Active syndromic surveillance was established by health departments in Milwaukee, Wisconsin; Denver, Colorado; Akron, Ohio; and Fort Worth, Texas. A total of 27 EDs reported syndrome frequencies from >146,000 patient encounters. CONCLUSIONS: ED and public health partners reported being satisfied with the system, confirming the usefulness of Internet tools in the rapid establishment of multiregion syndromic surveillance during an emerging global epidemic.

Guidelines for the grading of tinnitus severity: the results of a working group commissioned by the British Association of Otolaryngologists, Head and Neck Surgeons, 1999.

Tinnitus is a common experience with up to one third of the adult population experiencing it at some time in their life. Less than 1% of the adult population have tinnitus of sufficient severity to affect their quality of life seriously (although up to 8% may seek medical advice about it). Much of the severity of tinnitus relates to the individuals' psychological response to the abnormal tinnitus signal. The prevalence of tinnitus increases in association with high frequency hearing loss. There is, unfortunately, no diagnostic test that either confirms the presence of tinnitus or its severity. Currently there is no satisfactory severity grading system. A five-point severity grading scheme is therefore proposed and the entry criteria detailed. The five severity points are: slight, mild, moderate, severe and catastrophic. Categorization as 'severe' or 'catastrophic' should be, by epidemiological definition, very rare. General guidance, theory and evidential support are contained within.

Creutzfeldt-Jakob disease: the need to widen the differential diagnosis.

We report the case of a 76 year old woman who presented with a clinical picture initially typical of a vascular dementia. The diagnosis was revised to Creutzfeldt-Jacob Disease in the terminal stages. While Creutzfeldt-Jacob Disease is rare, one must consider it in the differential diagnosis as it can mimic other dementias particularly in the chronic form which we describe here.

12-O-tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Sp1 sites.

We have studied the effects of the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on Huntington's disease (HD) gene transcription in neuronal and non-neuronal cell lines, to investigate pathways regulating HD gene expression. TPA reduced transcription from the HD gene promoter in SK-N-SH (neuroblastoma) and HeLa cells but not in JEG3 (choriocarcinoma) cells. In SK-N-SH cells, the responsible cis-acting promoter sequences comprise the tandemly duplicated Sp1 sites in the region from -213 to -174, relative to the translation start site. The TPA-down-regulating region in HeLa cells was mapped to the sequence from -141 to -126. In conclusion, this demonstrates that HD gene transcription can be down-regulated in vitro in a cell-specific manner.

Guidelines on the diagnosis of noise-induced hearing loss for medicolegal purposes.

These guidelines aim to assist in the diagnosis of noise-induced hearing loss (NIHL) in medicolegal settings. The task is to distinguish between possibility and probability, the legal criterion being 'more probable than not'. It is argued that the amount of NIHL needed to qualify for that diagnosis is that which is reliably measurable and identifiable on the audiogram. The three main requirements for the diagnosis of NIHL are defined: R1, high-frequency hearing impairment; R2, potentially hazardous amount of noise exposure; R3, identifiable high-frequency audiometric notch or bulge. Four modifying factors also need consideration: MF1, the clinical picture; MF2, compatibility with age and noise exposure; MF3, Robinson's criteria for other causation; MF4, complications such as asymmetry, mixed disorder and conductive hearing impairment.

Transesophageal echocardiography in quantification of emboli during femoral nailing: reamed versus unreamed techniques.

We quantified the embolic load to the lungs created with two different techniques of femoral nailing. Eleven patients with 12 traumatic femur fractures were randomized to reamed (7 fractures) and unreamed (5 fractures) groups. Intramedullary nailing was with the AO/ASIF* universal reamed or unreamed nail. Transesophageal echocardiography (TEE) was used to evaluate the quantity and quality of emboli generated by nailing. Data were analyzed using software that digitized the TEE images and quantified the area of embolic particles in each frame. The duration of each level of embolic phenomena (zero, moderate, severe) was used to determine total embolic load with various steps (fracture manipulation, proximal portal opening, reaming, and nail passage). Manual grading of emboli correlated highly with software quantification. Our data confirm the presence and similarity of emboli generation with both methods of intramedullary nailing. Unreamed nails do not protect the patient from pulmonary embolization of marrow contents.

Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1.

The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.

Herpes simplex virus type 1-specific cytotoxic T-lymphocyte arming occurs within lymph nodes draining the site of cutaneous infection.

Various studies have shown that major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL) can be isolated from lymph nodes draining sites of cutaneous infection with herpes simplex virus type 1 (HSV-1). Invariably, detection of this cytolytic activity appeared to require some level of in vitro culture of the isolated lymph node cells, usually for 3 days, in the absence of exogenous viral antigen. This in vitro "resting" period was thought to represent the phase during which committed CD8(+) T cells become "armed" killers after leaving the lymph nodes and prior to their entry into infected tissue as effector CTL. In this study we reexamined the issue of CTL appearance in the HSV-1 immune response and found that cytolytic activity can be isolated directly from draining lymph nodes, although at levels considerably below those found after in vitro culture. By using T-cell receptor elements that represent effective markers for class I-restricted T cells specific for an immunodominant glycoprotein B (gB) determinant from HSV-1, we show that the increase in cytotoxicity apparent after in vitro culture closely mirrors the expansion of gB-specific CTL during the same period. Taken together, our results suggest that HSV-1-specific CTL priming does not appear to require any level of cytolytic machinery arming outside the lymph node compartment despite the absence of any detectable infection within that site.

A mutant of Mycobacterium smegmatis defective in dipeptide transport.

A mutant of Mycobacterium smegmatis unable to use the dipeptide carnosine (beta-alanyl-L-histidine) as a sole carbon or nitrogen source was isolated. Carnosinase activity and the ability to grow on beta-Ala and/or L-His were similar in the mutant and the wild type. However, the mutant showed significant impairment in the uptake of carnosine. This study is the first description of a peptide utilization mutant of a mycobacterium.

Functional analysis of the Huntington's disease (HD) gene promoter.

The basis for the highly specific neuronal vulnerability seen in Huntington's disease (HD) has not been determined. Recent studies have demonstrated that variation in HD protein expression occurs in the striatum, with affected regions showing increased HD immunoreactivity. Experiments in HD and SCA1 transgenic mice suggest a correlation between phenotypic severity and expression of the mutant transgene. To gain insights into control of HD gene expression, and to investigate the possibility of cell-cell differences in transcription, we have analysed the 5' upstream region of the HD gene in a neuronal (SK-N-SH) and a non-neuronal (JEG3) cell line. Reporter gene assays demonstrated the presence of a key positive-acting region apparently arising from two Sp1 sites in a tandem repeat acting synergistically. This site is polymorphic, and a single Sp1 site is associated with reduced levels of transcription. These experiments also reveal differences in control of expression between neuronal and non-neuronal cell lines.

The moral education of medical students.

The author begins his essay by discussing George Eliot's novel Middlemarch, in which a doctor, early in his career, wanders from his idealistic commitment to serving the poor. Although he establishes a prominent practice, he considers himself a failure because "he had not done what he once meant to do." The essay explores how many of us (physicians included) forsake certain ideals or principles--not in one grand gesture, but in moment-to-moment decisions, in day-to-day rationalizations and self-deceptions, until we find ourselves caught in lives whose implications we have long ago stopped examining, never mind judging. Medical education barrages students with information, fosters sometimes ruthless competition, and perpetuates rote memorization and an obsession with test scores--all of which stifle moral reflection. Apart from radically rethinking medical education (doing away with the MCAT, for example, as Lewis Thomas proposed), how can we teach students to consider what it means to be a good doctor? Calling upon the work of Eliot, Walker Percy, and others, the author discusses how the study of literature can broaden and deepen the inner lives of medical students and encourage moral reflectiveness.

Analysis of the 5' upstream sequence of the Huntington's disease (HD) gene shows six new rare alleles which are unrelated to the age at onset of HD.

The CAG repeat number in the Huntington's disease (HD) gene accounts for about 50% of the variation seen in age at onset of HD. In order to determine whether promoter sequence variation can contribute to the residual variation in age at onset, we studied the conserved 303 bp region upstream of the +1 translation start site in the HD gene in a population of 56 control East Anglians, 30 Africans, 34 Japanese, and 208 English Huntington's disease patients. A surprisingly high degree of variation was found. Seven alleles were identified, comprising four polymorphisms: two single base pair substitutions, a 6 bp VNTR present as one or two copies, and a 20 bp VNTR with one to three copies of the tandem repeat. No correlation between polymorphisms and age at onset of symptoms was found in HD patients. The 6 bp and 20 bp stretches are present only in single copies in the chimpanzees and gorilla, suggesting that these VNTRs have evolved by duplication of the core sequences in the human lineage.