Towards the automated identification of Chrysomya blow flies from wing images.

The Old World screwworm fly (OWSF), Chrysomya bezziana (Diptera: Calliphoridae), is an important agent of traumatic myiasis and, as such, a major human and animal health problem. In the implementation of OWSF control operations, it is important to determine the geographical origins of such disease-causing species in order to establish whether they derive from endemic or invading populations. Gross morphological and molecular studies have demonstrated the existence of two distinct lineages of this species, one African and the other Asian. Wing morphometry is known to be of substantial assistance in identifying the geographical origin of individuals because it provides diagnostic markers that complement molecular diagnostics. However, placement of the landmarks used in traditional geometric morphometric analysis can be time-consuming and subject to error caused by operator subjectivity. Here we report results of an image-based approach to geometric morphometric analysis for delivering wing-based identifications. Our results indicate that this approach can produce identifications that are practically indistinguishable from more traditional landmark-based results. In addition, we demonstrate that the direct analysis of digital wing images can be used to discriminate between three Chrysomya species of veterinary and forensic importance and between C. bezziana genders.

A randomised, phase II study of nintedanib or sunitinib in previously untreated patients with advanced renal cell cancer: 3-year results.

BACKGROUND: This exploratory study evaluated the safety/efficacy of nintedanib or sunitinib as first-line therapy in patients with advanced renal cell carcinoma (RCC). METHODS: Ninety-six patients were randomised (2:1) to either nintedanib (200 mg twice daily) or sunitinib (50 mg kg(-1) once daily (4 weeks on treatment; 2 weeks off)). Primary endpoint was progression-free survival (PFS) at 9 months. P-values reported are descriptive only; the study was not powered for such comparisons. RESULTS: Progression-free survival at 9 months was comparable between nintedanib and sunitinib (43.1% vs 45.2%, respectively; P=0.85). Median PFS was 8.4 months in each group (hazard ratio (HR), 1.12; 95% confidence interval (CI): 0.70-1.80; P=0.64). Median overall survival was 20.4 and 21.2 months for nintedanib and sunitinib, respectively (HR, 0.92; 95% CI: 0.54-1.56; P=0.76). Overall incidence of any grade adverse events (AEs) was comparable (90.6% vs 93.8%); AEs grade ⩾ 3 were lower with nintedanib than sunitinib (48.4% vs 59.4%). Nintedanib was associated with lower incidences of some AEs typical of antiangiogenic tyrosine kinase inhibitors (TKIs): hypertension, hypothyroidism, hand-foot syndrome, cardiac disorders and haematological abnormalities. CONCLUSIONS: In patients with advanced RCC, nintedanib has promising efficacy and similar tolerability to sunitinib, and a manageable safety profile with fewer TKI-associated AEs.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery.

We examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CDO2) in excess of that required by an increasing cerebral metabolic rate of oxygen ( CM RO2); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20-60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained CDO2 and elevated absolute CM RO2 at HA compared with SL, the relative increase in CM RO2 was similar during 20-80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain CDO2. Despite adequate CDO2 at HA the brain appears to increase non-oxidative metabolism during exercise and recovery.

Transpupillary collagen photocrosslinking for targeted modulation of ocular biomechanics.

The central vision-threatening event in glaucoma is dysfunction and loss of retinal ganglion cells (RGCs), thought to be promoted by local tissue deformations. Here, we sought to reduce tissue deformation near the optic nerve head by selectively stiffening the peripapillary sclera, i.e. the scleral region immediately adjacent to the optic nerve head. Previous scleral stiffening studies to treat glaucoma or myopia have used either pan-scleral stiffening (not regionally selective) or regionally selective stiffening with limited access to the posterior globe. We present a method for selectively stiffening the peripapillary sclera using a transpupillary annular light beam to activate methylene blue administered by retrobulbar injection. Unlike prior approaches to photocrosslinking in the eye, this approach avoids the damaging effects of ultraviolet light by employing red light. This targeted photocrosslinking approach successfully stiffened the peripapillary sclera at 6 weeks post-treatment, as measured by whole globe inflation testing. Specifically, strain was reduced by 47% when comparing treated vs. untreated sclera within the same eye (n = 7, p=0.0064) and by 54% when comparing the peripapillary sclera of treated vs. untreated eyes (n = 7, p<0.0001). Post-treatment characterization of RGCs (optic nerve axon counts/density, and grading), retinal function (electroretinography), and retinal histology revealed that photocrosslinking was associated with some ocular toxicity. We conclude that a transpupillary photocrosslinking approach enables selective scleral stiffening targeted to the peripapillary region that may be useful in future treatments of glaucoma.

A UK consensus on the management of the bladder in multiple sclerosis.

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients' continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.

Macroevolutionary interpretations of symmetry and synchroneity in the fossil record.

Quantitative analyses of global diversity in the marine fossil record over Phanerozoic time reveal an historically ordered pattern of sequential dominance and increasing diversity. Explanatory models applied to this empirical pattern lead to irreconcilable differences of interpretation. The issue may be resolved by determining the expected distributions and limits of temporal covariation among clades generated by a random branching process. Results also challenge the claim that asymmetries in intra-clade diversity variation provide a directional arrow for the history of life.

Prevention of protein denaturation during exposure to sterilization temperatures.

Firefly luciferase exposed to a temperature of 135 degrees C for 36 hours re tained up to 40 percent of its original activity. Prerequisites for heat stability were the use of a molecular sieve (Seph adex G-25 or Biogel P-300) and a high vacuum (5 x 10(-4) mm-Hg). These studies present a possible solution to the problem of sterilization for exobiologi cal experiments.

Eruption-triggered avalanche, flood, and lahar at mount st. Helens--effects of winter snowpack.

An explosive eruption of Mount St. Helens on 19 March 1982 had substantial impact beyond the vent because hot eruption products interacted with a thick snowpack. A blast of hot pumice, dome rocks, and gas dislodged crater-wall snow that avalanched through the crater and down the north flank. Snow in the crater swiftly melted to form a transient lake, from which a destructive flood and lahar swept down the north flank and the North Fork Toutle River.

A UK consensus on the management of the bladder in multiple sclerosis.

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients' continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.

Pain management in patients with malignant mesothelioma: challenges and solutions.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a considerable symptom burden and poor prognosis. Focus on maintaining patients' quality of life and pain control is therefore paramount. Pain management in MPM is complex due to its multifactorial etiology resulting from direct tumor infiltration of the surrounding soft tissue, bone, and encasement of the intercostal nerves. A variety of treatment modalities, including pharmacological and non-pharmacological options, are often required to achieve adequate pain control in this challenging disease. This review article examines the current challenges and solutions available for pain management in MPM.

Prediction of sublayer depth in turbid media using spatially offset Raman spectroscopy.

We demonstrate experimentally the feasibility of monitoring the depth of optically thick layers within turbid media using spatially offset Raman spectroscopy (SORS) in combination with multivariate analysis. The method uses the deep penetration capability of SORS to characterize significantly thicker (by at least a factor of 2) layers than possible with conventional Raman spectroscopy. Typical relative accuracies were between 5 and 10%. The incorporation of depth information into a SORS experiment as an additional dimension allows pure spectra of each individual layer to be resolved using three-dimensional multivariate techniques (parallel factor analysis, PARAFAC) to accuracies comparable with the results of a two-dimensional analysis.

SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma.

SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM). Standard palliative (20 Gy/5#) or dose escalated treatment (36 Gy/6#) will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM.

Microcracks in eggs.

An experimental program of mechanical testing has shown that microcracks initiate in hens' eggs at loads less than that necessary to cause total structural failure. In contact loading, computational modeling and numerical analysis show that very high stress levels develop on the inner surface of the eggshell as it conforms to a hard contact surface. This causes a series of microcracks to initiate at the inner surface of the shell and radiate out from the load site. A series of concentric circumferential microcracks also develop beneath the cuticle from the edge of the contact zone. Calculations relating to the eggshells' dynamic response indicate that microcracks have a little effect on the structural stiffness and resonant frequencies of the egg. As a result, microcracks are unlikely to be detected by online crack detection systems, which rely on mechanical excitation. Eggs in retail outlets are likely to contain microcracks as a result of insults experienced during the collection, grading, and packing processes. Because the eggshell forms the first line of defense against potentially pathogenic microorganisms entering the egg contents, microcracks could potentially compromise egg safety.

The role of stasis in the clotting of blood and milk flows around solid objects.

A milk preparation has been used previously as an analogue for the study of flow related thrombosis in vitro. This paper describes further experiments to determine the comparability of milk clotting and thrombosis and to investigate the hydrodynamic correlates of milk clot deposition. An objective was to establish a standard in vitro test for thrombogenicity, thus facilitating the search for athrombogenic designs for prosthetic valves and other devices. Milk clotting in steady and pulsatile flow around four simple bodies of revolution showed many similarities of location and extent with in vivo canine thrombosis formation around similar bodies. A dye injection investigation of the fluid residence time distribution under the hydrodynamic conditions of the milk flow experiments showed that a permanent or trapped vortex persisted at each downstream site where clot was found, implying that stasis, or stagnation, is of predominant importance in causing milk clotting. Supplementary experiments with milk, using a modified Lee-White test, likewise showed that mixing promoted coagulation only after a certain fixed induction period from activation of the clotting process. Thus clot deposition is promoted by mixing which follows a constant induction period, rather than by mixing during an induction phase. This is a significant modification of the previous hypothesis.

A blood analogue for the experimental study of flow-related thrombosis at prosthetic heart valves.

It is shown that a flowing mixture of unpasteurised cow's milk, rennet and calcium chloride will deposit solid clot in vitro in the neighbourhood of certain kinds of flow obstruction and hydrodynamic disturbance particularly associated with deposition and thrombus formation in a similar stream of blood. The milk and blood deposits are similar in physical structure, both on a microscopic and a gross scales. For established kinds of artificial heart valves, the growth sequence and developed patterns of milk clotting obtained in vitro with pulsatile flows at physiological rates closely resemble patterns of thrombus reported clinically for valves of the same type in vivo. It appears that these phenomena, for which a tentative explanation is outlined, can form the basis of a convenient and rapid experimental method for evaluating in vitro the effects of design changes on the thrombogenicity of artificial heart valves and other cardiovascular devices in vivo. The milk system also shows promise as an aid in fundamental experimental studies of mechanisms of flow-related thrombosis.

An electrophysiological study of the accessory olfactory bulb in the rabbit--I. Analysis of electrically evoked potential fields.

Following electrical stimulation of the vomeronasal nerves, the primary olfactory nerves, the lateral olfactory tract and the corticomedial amygdala, we have made a study of evoked potentials in the rabbit accessory olfactory bulb. Vomeronasal nerve stimulation evoked a complex field potential consisting of a compound action potential followed by 4 negative waves (N1, N2, N3, N4). In contrast to the field potential elicited in the main olfactory bulb following primary olfactory nerve stimulation, there was either no evoked wave or only a weak positive component of the field in the accessory bulb. Amygdala stimulation caused a long latency, long duration negative-positive dipolar field potential in the accessory olfactory bulb. Both antidromic and orthodromic field potentials showed sign reversal when the electrode penetrated the bulb at a point corresponding to the lower border of the mitral cell band. Stimulation of the lateral olfactory tract elicited a weak, short-latency wave which did not show any sign reversal when the electrode was lowered into the accessory bulb. This wave was presumably due to fibres arising in the main bulb and projecting through the accessory bulb into the lateral olfactory tract. Electrical stimulation of the primary olfactory nerves did not induce any response in the accessory bulb neither did vomeronasal nerve stimulation evoke a response in the main olfactory bulb. The origin of these potential fields is discussed and it is concluded that the synaptic organization of the accessory olfactory bulb resembles that of the main olfactory bulb in lower vertebrates. There is no detectable communication between the two olfactory systems.

Electrophysiological properties of nigrothalamic neurons after 6-hydroxydopamine lesions in the rat.

Extracellular recordings were made from electrophysiologically identified nigrothalamic cells in the substantia nigra pars reticulata of anaesthetized rats. The firing rate, firing pattern and responses to striatal stimulation were investigated in normal animals and in animals in which dopamine concentration in the ipsilateral striatum was reduced by more than 90%. At relatively short times after the lesion (less than 10 days) the mean firing rate of the spontaneously active cells in the population was significantly reduced and there was an increase in the occurrence of bursting activity. There was also a significant increase in the number of silent cells, located by antidromic stimulation from the thalamus. In spite of this reduction in mean firing rate the responses of neurons to stimulation of either the ipsilateral striatum or ventromedial thalamus was much larger in cells from lesioned animals. At longer times after the lesion (more than six months) the average firing rate of the neurons had returned to normal but there was still a prevalence of bursting activity and a consequent reduction in mean inter-spike intervals. There was little evidence of the previous hyper-responsiveness to thalamic stimulation but the responsiveness to striatal stimulation was still significantly elevated.

An electrophysiological study of the accessory olfactory bulb in the rabbit--II. Input-output relations as assessed from analysis of intra- and extracellular unit recordings.

The input-output relations of the rabbit accessory olfactory bulb were studied by intra- and extracellular single unit recordings following electrical stimulation of the vomeronasal nerves, the lateral olfactory tract and the corticomedial amygdala. Cellular activity of accessory bulb mitral cells evoked by stimulation of the vomeronasal nerves consisted of a brief excitation with a latency of 16 ms. This initial response was followed by a period of reduced firing probability which was due to an inhibitory postsynaptic potential. In many cases this secondary response was followed by a second excitatory postsynaptic potential on which action potentials were generated at higher stimulus intensities. Deeper cells in the granule cell layer responded with a long latency, long duration, excitation, often consisting of bursts of 2-3 spikes. The majority of mitral cells were antidromically invaded by amygdala stimulation. The latencies of the antidromic spikes showed a wide range of variation (12-80 ms). Due to this great variation in antidromic latency the inhibitory postsynaptic potential following the antidromic action potential was rather modest but prolonged in duration. In many cases the onset of the inhibitory postsynaptic potential preceded the antidromic response. The majority of cells did not respond to lateral olfactory tract stimulation. Only 10% of the tested cells were invaded antidromically by stimulation at this site. These neurons were also driven antidromically by amygdala stimulation. We conclude that, although the physiological characteristics of mitral cells of the main and accessory olfactory bulb are very similar, there are important differences. The efferent fibres of the accessory bulb conduct at very slow and variable rates and project directly to the corticomedial amygdala.

Distribution and synaptic contacts of the cortical terminals arising from neurons in the rat ventromedial thalamic nucleus.

Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin within the ventromedial thalamic nucleus resulted in many filled fibres in the frontal areas of rat cerebral cortex. The fibres were restricted to the upper part of layer I except in a small area of motor cortex where terminals were also found in deeper layers. Terminals were also seen in the striatum, in parts of the mesencephalic reticular formation and occasionally in the contralateral ventromedial nucleus. There is some topographical order in the projection with medial and dorsal areas well represented in medial cortex while lateral parts of ventromedial nucleus are more directly related to the cortical area that receives the ventrolateral thalamic nucleus projection. Electron microscopic examination showed the terminals in layer I of cortex making synaptic contact with dendritic spines and small dendritic profiles that showed a very dense postsynaptic specialization. Neurons in the ventromedial nucleus could be antidromically driven from electrode positions along strips of cortex which could not be easily related to any known organizational pattern in the cortex. Thalamic neurons responding antidromically to only one stimulation site were more common when the stimulation was within motor cortical areas, suggesting that in this region a more restricted pattern of termination is the rule.