Design of achromatic diffractive lenses.

Diffractive lenses can be very thin and light. They usually suffer from chromatic aberration and work only over a narrow range of wavelengths but so-called achromatic diffractive lenses have recently attracted attention. Ways in which the profile of such lenses can be chosen to optimize either the Strehl ratio or the efficiency are compared and the extent to which the performance of the resulting lens designs approaches theoretical limits is investigated. Simple rules are given for the average Strehl ratio and efficiency expected in certain conditions. In other cases they provide approximate guidelines. Some reported simulated and measured efficiencies greatly exceed those that appear credible. This is attributed to failure to take into account radiation scattered to large off-axis angles or to inadequate sampling of the radial profile.

Towards a standardized framework for AI-assisted, image-based monitoring of nocturnal insects.

Automated sensors have potential to standardize and expand the monitoring of insects across the globe. As one of the most scalable and fastest developing sensor technologies, we describe a framework for automated, image-based monitoring of nocturnal insects-from sensor development and field deployment to workflows for data processing and publishing. Sensors comprise a light to attract insects, a camera for collecting images and a computer for scheduling, data storage and processing. Metadata is important to describe sampling schedules that balance the capture of relevant ecological information against power and data storage limitations. Large data volumes of images from automated systems necessitate scalable and effective data processing. We describe computer vision approaches for the detection, tracking and classification of insects, including models built from existing aggregations of labelled insect images. Data from automated camera systems necessitate approaches that account for inherent biases. We advocate models that explicitly correct for bias in species occurrence or abundance estimates resulting from the imperfect detection of species or individuals present during sampling occasions. We propose ten priorities towards a step-change in automated monitoring of nocturnal insects, a vital task in the face of rapid biodiversity loss from global threats. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma.

BACKGROUND: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. MATERIALS AND METHODS: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). RESULTS: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. CONCLUSIONS: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.

Effect of media, additives, and incubation conditions on the recovery of high pressure and heat-injured Clostridium botulinum spores.

The effect of additives and post-treatment incubation conditions on the recovery of high pressure and heat-injured (i.e., processed at 620 MPa and 95 and 100 degrees C for 5 min) spores of Clostridium botulinum strains, 62-A (proteolytic type A) and 17-B (nonproteolytic type B) was studied. High pressure and heat-injured spores were inoculated into TPGY (Trypticase-Peptone-Glucose-Yeast extract) anaerobic broth media containing additives (lysozyme, L-alanine, L-aspartic acid, dipicolonic acid, sodium bicarbonate, and sodium lactate) at various concentrations (0-10 microg/ml) individually or in combination. The spore counts of high pressure and heat-injured 62-A and 17-B recovered from TPGY broth containing lysozyme (10 microg/ml) incubated for 4 months versus that recovered from peptone-yeast extract-glucose-starch (PYGS) plating agar containing lysozyme (10 microg/ml) incubated under anaerobic conditions for 5 days were also compared. None of the additives either individually or in combination in TPGY broth improved recovery of injured spore enumeration compared to processed controls without additives. Addition of lysozyme at concentrations of 5 and 10 microg/ml in TPGY broth improved initial recovery of injured spores of 17-B during the first 4 days of incubation but did not result in additional recovery at the end of the 4 month incubation compared to the processed control without lysozyme. Adding lysozyme at a concentration of 10 microg/ml to PYGS plating agar resulted in no effect on the recovery of high pressure and heat-injured 62-A and 17-B spores. The recovery counts of high pressure and heat-injured spores of 62-A and 17-B were lower (i.e., <1.0 log units) with PYGS plating agar compared to the MPN method using TPGY broth as the growth medium.

Participatory epidemiology in disease surveillance and research.

Participatory epidemiology is the application of participatory methods to epidemiological research and disease surveillance. It is a proven technique which overcomes many of the limitations of conventional epidemiological methods, and has been used to solve a number of animal health surveillance and research problems. The approach was developed in small-scale, community animal health programmes, and then applied to major international disease control efforts. The Global Rinderpest Eradication Program adopted participatory epidemiology as a surveillance tool for controlling rinderpest. This approach was subsequently used in both rural and urban settings in Africa and Asia, for foot and mouth disease, peste des petits ruminants and highly pathogenic avian influenza. Participatory disease surveillance has made an important contribution towards controlling both rare and common diseases. This paper reviews the principal applications of participatory epidemiology and highlights the lessons learned from field applications. In addition, the authors examine future challenges and consider new areas for research.

A kinetic study of the photochemical inactivation of adenylate kinases of Mycobacterium marinum and bovine heart mitochondria.

Using incident light energy of about 76 mW.cm-2 in a dye-sensitized photooxidation reaction, we have investigated the possible involvement of one or both of the histidine residues in the catalytic activity of adenylate kinase (ATP:AMP phosphotransferase) of Mycobacterium marinum. We have done this by investigating the kinetics of photochemical inactivation of the enzyme. At pH 7.4, the kinetics of photoinactivation are biphasic with two different pseudo-first-order rate constants. Adenosine 5'-pentaphospho 5'-adenosine (Ap5A), ATP and, to some extent, AMP, all gave protection to the enzyme from inactivation. Amino-acid analysis of the photoinactivated enzyme indicated the loss of the two histidine residues. This, and the fact that photoinactivation occurred faster at alkaline compared to acidic pH, indicated the involvement of the histidine residues in the catalytic activity. A mathematical model is developed which assumes that both histidine residues are required for maximal catalytic activity: one is located peripherally, is exposed, and therefore is readily photooxidized (pseudo-first-order rate constant, k1 = 1.3.10(-2)s-1), while the other is located at the active site, involved in substrate-binding and is shielded (pseudo-first-order rate constant, k2 = 2.9.10(-4)s-1). However, this shielded histidine could be exposed and made more accessible to photooxidation either by raising the pH above 10, or alternatively, by the addition of 8 M acetamide (or 6 M guanidine). Under these conditions, which apparently cause unfolding of the protein molecule, the kinetics of photoinactivation change from biphasic to monophasic, suggesting that both histidine residues are equally exposed and are photooxidized at the same rate. Unlike the enzyme from M. marinum, adenylate kinase from bovine heart mitochondria shows monophasic kinetics of photoinactivation at pH 7.4, suggesting that only one of the six histidine residues is essential for catalytic activity, or if more than one, then they all must be equally exposed. Further, ATP, AMP or Ap5A did not provide protection against photoinactivation, suggesting that the histidine residue(s) involved in the catalytic activity must remain exposed after the substrates bind at the active site of the mitochondrial enzyme.

Provider-patient communication and metabolic control.

OBJECTIVE: To determine whether nurses' and NIDDM patients' communication styles during consultations are related to subsequent metabolic control and to examine factors influencing patterns of communication in these consultations. RESEARCH DESIGN AND METHODS: A total of 47 NIDDM patients participated in the study and completed the following procedures: 1) assessment of baseline HbA1, 2) attended 3.5 days of diabetes education, 3) returned in 1 mo for a follow-up consultation with a nurse, and (4) returned in 9-12 wk for a follow-up HbA1 assessment. The communication variables coded from the consultations were the frequency with which nurses produced controlling, informative, and patient-centered utterances and the frequency with which patients sought information, engaged in decision making, and expressed negative affect. RESULTS: The results were as follows: 1) patients experienced poorer metabolic control after interacting with nurses who were more controlling and directive in their communication with patients (r = 0.39, P < 0.01); 2) the nurses' use of patient-centered responses was directly related to the degree to which patients expressed feelings (r = 0.34, P < 0.01) and exhibited decision-making behavior (r = 0.62, P < 0.01); and 3) several of the nurses' and patients' communicative behaviors were related to patient characteristics such as age, sex, education, and baseline HbA1 levels. CONCLUSIONS: The results suggest that providers' attempts to exert considerable control during consultations with NIDDM patients may be counterproductive and contribute to poorer outcomes. The findings also indicate that patient-centered behaviors (e.g., encouraging the patient's involvement, respecting the patient's opinion, and offering support) facilitate the patient's ability to be an active participant in the consultation.

Glycoprotein patterns in normal and malignant cervical tissue.

Glycoproteins from normal and malignant human cervix were studied using an organ culture system and compared by gel electrophoresis and autoradiography. Five glycoproteins of 178 kDa, 95 kDa, 93 kDa, 82 kDa and 38 kDa and 1 glycolipid (46 kDa) were detected more frequently in squamous carcinomas. Certain glycoproteins were shown to be oncofoetal and some had affinity for Concanavalin A (Con A). The 82 kDa glycoprotein was present in 16/17 squamous carcinomas but in only 1/13 normal cervices. This band represented a glycoprotein containing glucosamine, mannose, small quantities of methionine and no fucose. These preliminary results suggest that these glycoproteins and in particular the 82-kDa glycoprotein are worthy of further investigation and characterisation.

Antiviral properties of extract of Opuntia streptacantha.

An extract of the cactus plant Opuntia streptacantha inhibited intracellular virus replication and inactivated extracellular virus. Inhibition of virus replication also occurred following pre-infection treatment--a favourable finding in terms of in-vivo limitation of virus disease. There was inhibition of both DNA and RNA virus replication, for example, herpes simplex virus, equine herpes virus, pseudorabies virus, influenza virus, respiratory syncytial virus and human immunodeficiency virus, with normal protein synthesis in uninfected cells at extract concentrations which were 15-fold in excess of 50% viral inhibitory concentrations (1 mg/ml). The active inhibitory component(s) of the extract appeared to be protein in nature and resided mainly in the wall of the plant rather than in the cuticle or inner sap. The extract was non-toxic on oral administration to mice, horses and human patients; the non-toxicity of intravenous administration of 70 mg to a mouse representing at least fifty tissue culture 50% viral inhibitory dosages encourages clinical trial of this extract in virus disease of human and veterinary species.

A system for isolation, transport and storage of herpes simplex viruses.

A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 degrees C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.

Experimental ulcerative herpetic keratitis. IV. Preliminary observations on the efficacy of a herpes simplex subunit vaccine.

Systemic vaccination of rabbits with an inactivated type 1 virus subunit vaccine induced humoral and cell-mediated immune responses. Following ocular infection with type 1 herpes virus corneal ulceration and virus excretion were reduced in the vaccinated rabbits.

An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts.

An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine.

The infrequency of transmission of herpesviruses between humans and animals; postulation of an unrecognised protective host mechanism.

The infrequency of natural transmission of herpesviruses between humans and animals is surprising as there is extensive contact between humans and non-human species with unequivocal evidence that host cells from non-susceptible species will support replication of herpesviruses which do not seem to naturally infect that species. This review examines natural cross-infections between human and other species and suggests that, firstly, it is possible that humans and animals do become asymptomatically or symptomatically cross-infected from other species, but the infection is not diagnosed or not diagnosable by conventional methods; secondly, an as yet unidentified novel mechanism(s) may operate to prevent infection using chemical, electrical or as yet unidentified pathways and may even be 'switched on' by exposure to the virus.

A virus-particle vaccine prepared from bovine mammillitis virus against herpes genitalis.

A vaccine against herpes genitalis was prepared from the extracellular virus particles from baby hamster kidney cells infected with bovine mammillitis virus (BMV) strain "Allerton". The virus was inactivated by formaldehyde followed by ultracentrifugation to concentrate the virus particles and eliminate formaldehyde to an acceptable concentration for immunisation of human subjects. The vaccine was cross antigenic and cross immunogenic with herpes simplex virus type 1. Thirty-four consorts at high risk of herpes genitalis were immunised with two or three doses each containing 10(9) virus particles equialent to approx. 150 micrograms protein. There has been no evidence of local or general side effect in a follow-up period of over 100 patient years. The immunogenicity and protective efficacy of this vaccine in human subjects will be investigated in a double-blind placebo-controlled trial.

Conservative prediction of time to Clostridium botulinum toxin formation for use with time-temperature indicators to ensure the safety of foods.

Integrating-type time-temperature indicators (TTIs) may be utilized to warn food processors and consumers about storage conditions that may have rendered a food potentially hazardous. As an example of how integrated TTIs could be manufactured to emulate an infinite set of time-temperature situations, a set of conditions which have supported C. botulinum growth and toxin production was compiled. The time-temperature curve representing conservative times required for toxin formation was constructed with data from literature relating to toxin formation as a function of temperature in any media or food product. This set of critical time-temperature data is fit by a conservative empirical relationship that can be used to predict combinations of incubation times and storage temperatures that represent a potential health risk from C. botulinum in foods. A TTI could be constructed to indicate deviation from such a given set of conditions to bring attention to foods that may have been exposed to potentially hazardous temperatures with respect to C. botulinum toxin formation.

Differentiation between types and strains of Clostridium botulinum by riboprinting.

The ability of automated ribotyping to differentiate between major types and individual strains of Clostridium botulinum was tested using the Qualicon Riboprinter Microbial Characterization System. Pure spores of C. botulinum type A, proteolytic type B, nonproteolytic type B, and type E strains were inoculated onto modified anaerobic egg yolk agar and incubated 24 h at 35 degrees C. Plates were rinsed with buffer (2 mM Tris + 20 mM EDTA) to remove vegetative cells that were heated for 10 min at 80 degrees C, treated with a lysing agent, and ribotyped in the Qualicon Riboprinter utilizing the enzyme EcoRI. Riboprint patterns were obtained for 30 strains of the four major types of C. botulinum most commonly involved in human foodborne botulism. Proteolytic strains yielded the best and most consistent results. Fifteen ribogroups were identified among the 31 strains tested. Interestingly, in two cases, a single ribogroup contained patterns from isolates belonging to evolutionarily distinct Clostridium lineages. This degree of differentiation between strains of C. botulinum may be useful in hazard analysis and identification, hazard analysis and critical control point monitoring and validation, environmental monitoring, and in inoculation studies.

Improved high-intensity microwave discharge lamp for atomic resonance absorption and fluorescence spectrometry.

An unusually good combination of high intensity and narrow line has been achieved in a microwave discharge lamp by placing the optical window in the center of the microwave cavity. Construction details and performance characteristics are described.

Cytologic evaluation of experimental type 2 herpes simplex infection in mice.

The nature and frequency of cytopathologic changes in female mice genitally infected with type 2 herpes simplex virus have been investigated. The extent of virus infection in an individual mouse was assessed by a system of "plus scoring". Exfoliative cytology clearly provided a reliable evaluation of the extent of virus infection and a reliable prognostic index of mouse mortality. A composite index combining both cytologic and virologic information ('vircyt' value) was derived and shown to provide a convenient and precise prognostic index of mouse mortality.

Site-specific adaptive remodeling of Greyhound metacarpal cortical bone subjected to asymmetrical cyclic loading.

OBJECTIVE: To quantify geometric, inertial, and histomorphometric properties at the mid-diaphyseal level of left and right metacarpal bones (MCB) of racing Greyhounds. SAMPLE POPULATION: MCB from 7 racing Greyhounds euthanatized for reasons unrelated to MCB abnormalities. PROCEDURES: Mid-diaphyseal transverse sections of left and right MCB were stained with H&E or microradiographed. Images of stained sections were digitized, and cross-sectional area, cortical area, and maximum and minimum area moments of inertia of each bone were determined. Histomorphometric data (osteonal density, osteonal birefringence, and endosteal new lamellar bone thickness) were collected in 4 quadrants (dorsal, palmar, lateral, medial). Values were compared between limbs and among bones and quadrants. RESULTS: Cross-sectional area, cortical area, and maximum and minimum moments of inertia of left MCB-IV and -V were significantly greater, compared with contralateral bones. Overall osteonal densities in the dorsal quadrants of left MCB were greater, compared with lateral and medial quadrants. Also, percentage of birefringent osteons was significantly greater in the dorsal quadrant of left MCB-III, -IV, and -V, compared with the palmar quadrant. Thickness of new endosteal lamellar bone was not significantly influenced by limb, bone, or quadrant. CONCLUSIONS AND CLINICAL RELEVANCE: Increased cortical thickness and geometric properties of left MCB-IV and -V of Greyhounds, together with altered turnover and orientation of osteons in the dorsal quadrants of left MCB, are site-specific adaptive responses associated with asymmetric cyclic loading as a result of racing on circular tracks. Site-specific adaptive remodeling may be important in the etiopathogenesis of fatigue fractures in racing Greyhounds.

Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods.

As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (ΣR), and preventing an increase in levels (ΣI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods.