Tetanus prophylaxis in horses: guidelines for New Zealand and Australia based on a critical appraisal of the evidence.

Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.

Measuring the Joint Spectral Mode of Photon Pairs Using Intensity Interferometry.

The ability to manipulate and measure the time-frequency structure of quantum light is useful for information processing and metrology. Measuring this structure is also important when developing quantum light sources with high modal purity that can interfere with other independent sources. Here, we present and experimentally demonstrate a scheme based on intensity interferometry to measure the joint spectral mode of photon pairs produced by spontaneous parametric down-conversion. We observe correlations in the spectral phase of the photons due to chirp in the pump. We show that our scheme can be combined with stimulated emission tomography to quickly measure their mode using bright classical light. Our scheme does not require phase stability, nonlinearities, or spectral shaping and thus is an experimentally simple way of measuring the modal structure of quantum light.

Single-shot discrimination of coherent states beyond the standard quantum limit.

The discrimination of coherent states is a key task in optical communication and quantum key distribution protocols. In this work, we use a photon-number-resolving detector, the transition-edge sensor, to discriminate binary-phase-shifted coherent states at a telecom wavelength. Owing to its dynamic range and high efficiency, we achieve a bit error probability that unconditionally exceeds the standard quantum limit (SQL) by up to 7.7 dB. The improvement to the SQL persists for signals containing up to approximately seven photons on average and is achieved in a single shot (i.e., without measurement feedback), thus making our approach compatible with larger bandwidths.

The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Pigmented purpuric dermatosis in children: a retrospective cohort with emphasis on treatment and outcomes.

BACKGROUND: Data regarding the course and treatment of pigmented purpuric dermatoses (PPD) in the paediatric population are limited. Although treatments for pigmented purpura are not well established, vitamin C and rutoside have been reported to be an effective treatment option and are widely utilized. OBJECTIVE: To assess the clinical course and utility of vitamin C and rutoside in paediatric patients with PPD treated at Ann & Robert H. Lurie Children's Hospital of Chicago between 2008 and 2018. METHODS: A retrospective review of all children with PPD managed at our hospital between 2008 and 2018 was performed. Additional follow-up was obtained via telephone interviews. RESULTS: A total of 101 patients met inclusion criteria. The female: male ratio was 1.3 : 1, and the median age at diagnosis was 8.8 years (IQR, 5.7-12.9). Median follow-up was 7.13 months (IQR, 3-17.4). The most common PPD subtypes were lichen aureus (43%) and Schamberg (34%). Fifty-three (52%) patients had evaluable follow-up documentation via their medical record or phone questionnaire. Twenty-eight patients were treated with vitamin C or rutoside or combination therapy. Twenty-five patients received no treatment. Clearance of the rash was noted in 24 (45.3%) patients overall, including 10 (42%) patients in the treated group and 14 (58%) patients in the untreated group. Recurrence was noted in seven (13.2%) patients. Treatment with vitamin C and/or rutoside was well tolerated without side effects. None of the patients were subsequently diagnosed with vasculitis, coagulopathy or cutaneous T-cell lymphoma. CONCLUSION: Pigmented purpuric dermatosis in children is a benign disorder with high rates of complete resolution. Treatment with vitamin C and rutoside is well tolerated, but in this cohort, there did not appear to be an advantage over watchful waiting without therapy.

Quantum-enhanced interferometry with large heralded photon-number states.

Quantum phenomena such as entanglement can improve fundamental limits on the sensitivity of a measurement probe. In optical interferometry, a probe consisting of N entangled photons provides up to a N enhancement in phase sensitivity compared to a classical probe of the same energy. Here, we employ high-gain parametric down-conversion sources and photon-number-resolving detectors to perform interferometry with heralded quantum probes of sizes up to N = 8 (i.e. measuring up to 16-photon coincidences). Our probes are created by injecting heralded photon-number states into an interferometer, and in principle provide quantum-enhanced phase sensitivity even in the presence of significant optical loss. Our work paves the way towards quantum-enhanced interferometry using large entangled photonic states.

Travel time to health facilities in areas of outbreak potential: maps for guiding local preparedness and response.

BACKGROUND: Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. METHODS AND FINDINGS: We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. CONCLUSIONS: These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country's preparedness plans.

Influence of early-life nutritional stress on songbird memory formation.

In birds, vocal learning enables the production of sexually selected complex songs, dialects and song copy matching. But stressful conditions during development have been shown to affect song production and complexity, mediated by changes in neural development. However, to date, no studies have tested whether early-life stress affects the neural processes underlying vocal learning, in contrast to song production. Here, we hypothesized that developmental stress alters auditory memory formation and neural processing of song stimuli. We experimentally stressed male nestling zebra finches and, in two separate experiments, tested their neural responses to song playbacks as adults, using either immediate early gene (IEG) expression or electrophysiological response. Once adult, nutritionally stressed males exhibited a reduced response to tutor song playback, as demonstrated by reduced expressions of two IEGs (Arc and ZENK) and reduced neuronal response, in both the caudomedial nidopallium (NCM) and mesopallium (CMM). Furthermore, nutritionally stressed males also showed impaired neuronal memory for novel songs heard in adulthood. These findings demonstrate, for the first time, that developmental conditions affect auditory memories that subserve vocal learning. Although the fitness consequences of such memory impairments remain to be determined, this study highlights the lasting impact early-life experiences can have on cognitive abilities.

Shape-preserving and unidirectional frequency conversion by four-wave mixing.

In this work, we investigate the properties of four-wave mixing Bragg scattering driven by orthogonally polarized pumps in a birefringent waveguide. This configuration enables a large signal conversion bandwidth, and allows strongly unidirectional frequency conversion as undesired Bragg-scattering processes are suppressed by waveguide birefringence. Moreover, we show that this form of Bragg scattering preserves the (arbitrary) signal pulse shape, even when driven by pulsed pumps.

Bacterial testing of platelets - has it prevented transfusion-transmitted bacterial infections in Australia?

BACKGROUND AND OBJECTIVES: Australia introduced bacterial contamination screening (BCS) for platelet components in April 2008. This study presents analysis performed to assess the efficacy of testing. MATERIALS AND METHODS: Seven-day aerobic and anaerobic culture is performed using the BacT/ALERT 3D system. Following an initial machine positive (IMP) flag, all associated components are recalled, and/or clinicians treating already transfused patients are notified. IMPs are categorized as 'machine false positive', 'confirmed positive' or 'indeterminate' depending on culture results of initial and repeat samples. RESULTS: Between 2010 and 2012, 1·1% of platelet donations tested IMP; since 2013, this rate has fallen to 0·6% through improved instrument management, reducing false-positive IMPs but maintaining sensitivity for cultures yielding bacterial growth. On average, 66% of confirmed positive and indeterminate platelet units had been transfused at the time of detection. The majority (95%) of these grew Propionibacterium sp., a slow-growing organism that rarely causes sepsis in the transfusion setting. The incidence of reported transfuion-transmitted bacterial infection (TTBI) has fallen since the introduction of BCS, with a 4·2-fold [0·5, 28·2] lower rate from platelets. CONCLUSION: BCS has been successful in detecting platelet units containing pathogenic bacteria. The incidence of TTBI from platelets has fallen since the introduction of BCS, but the risk has not been eliminated due to rare false-negative results. In the absence of a pathogen inactivation system for red blood cells, BCS provides 'surrogate' testing of red blood cells from which platelets have been manufactured.

Indistinguishable heralded single photon generation via relative temporal multiplexing of two sources.

Generating N single photons simultaneously is a formidable challenge due to the lack of deterministic single photon sources. Recent work [New J. Phys. 19, 063013 (2017] has proposed a relative multiplexing scheme that can enhance the N single photons probability with a minimum of active switching resources. We experimentally demonstrate relative temporal multiplexing on two photon sources with a 90% additional enhancement over the standard temporal multiplexing scheme demonstrated previously. 88 ± 11% visibility of Hong-Ou-Mandel quantum interference verifies the indistinguishability of the heralded single photons after the synchronization. This proof-of-principle demonstration points out the potential significance of the relative multiplexing scheme for large-scale photonic quantum information processing.

Instrument flight to the inner ear.

Surgical robot systems can work beyond the limits of human perception, dexterity and scale making them inherently suitable for use in microsurgical procedures. However, despite extensive research, image-guided robotics applications for microsurgery have seen limited introduction into clinical care to date. Among others, challenges are geometric scale and haptic resolution at which the surgeon cannot sufficiently control a device outside the range of human faculties. Mechanisms are required to ascertain redundant control on process variables that ensure safety of the device, much like instrument-flight in avionics. Cochlear implantation surgery is a microsurgical procedure, in which specific tasks are at sub-millimetric scale and exceed reliable visuo-tactile feedback. Cochlear implantation is subject to intra- and inter-operative variations, leading to potentially inconsistent clinical and audiological outcomes for patients. The concept of robotic cochlear implantation aims to increase consistency of surgical outcomes such as preservation of residual hearing and reduce invasiveness of the procedure. We report successful image-guided, robotic CI in human. The robotic treatment model encompasses: computer-assisted surgery planning, precision stereotactic image-guidance, in-situ assessment of tissue properties and multipolar neuromonitoring (NM), all based on in vitro, in vivo and pilot data. The model is expandable to integrate additional robotic functionalities such as cochlear access and electrode insertion. Our results demonstrate the feasibility and possibilities of using robotic technology for microsurgery on the lateral skull base. It has the potential for benefit in other microsurgical domains for which there is no task-oriented, robotic technology available at present.

Experimental verification of multipartite entanglement in quantum networks.

Multipartite entangled states are a fundamental resource for a wide range of quantum information processing tasks. In particular, in quantum networks, it is essential for the parties involved to be able to verify if entanglement is present before they carry out a given distributed task. Here we design and experimentally demonstrate a protocol that allows any party in a network to check if a source is distributing a genuinely multipartite entangled state, even in the presence of untrusted parties. The protocol remains secure against dishonest behaviour of the source and other parties, including the use of system imperfections to their advantage. We demonstrate the verification protocol in a three- and four-party setting using polarization-entangled photons, highlighting its potential for realistic photonic quantum communication and networking applications.

Measurement of Intraspinal Pressure After Spinal Cord Injury: Technical Note from the Injured Spinal Cord Pressure Evaluation Study.

Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI.

Waveform Analysis of Intraspinal Pressure After Traumatic Spinal Cord Injury: An Observational Study (O-64).

Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.

Opportunities and dangers for neurosurgery in the current NHS.

The NHS is entering a third decade of administrative turbulence and cost pressures and many view the new NHS structure and systems as complex and confusing. Health and social care budgets are being merged in some geographical areas and large efficiency savings are needed by 2020. There are risks that lie ahead for neurosurgery and our patients if the specialty becomes further fragmented and opportunities for positive change are missed. One of the new care models proposed in the NHS five year plan is specialist care provided across multiple hospital sites by a single overarching specialist trust, mirroring ophthalmology where the Moorfields trust provides specialist eye services in over 20 locations in London and the South East. This model lends itself to adoption by neurosurgery and has the potential to increase standards, efficiency, training and research.

Intraspinal pressure and spinal cord perfusion pressure after spinal cord injury: an observational study.

OBJECT: In contrast to intracranial pressure (ICP) in traumatic brain injury (TBI), intraspinal pressure (ISP) after traumatic spinal cord injury (TSCI) has not received the same attention in terms of waveform analysis. Based on a recently introduced technique for continuous monitoring of ISP, here the morphological characteristics of ISP are observationally described. It was hypothesized that the waveform analysis method used to assess ICP could be similarly applied to ISP. METHODS: Data included continuous recordings of ISP and arterial blood pressure (ABP) in 18 patients with severe TSCI. RESULTS: The morphology of the ISP pulse waveform resembled the ICP waveform shape and was composed of 3 peaks representing percussion, tidal, and dicrotic waves. Spectral analysis demonstrated the presence of slow, respiratory, and pulse waves at different frequencies. The pulse amplitude of ISP was proportional to the mean ISP, suggesting a similar exponential pressure-volume relationship as in the intracerebral space. The interaction between the slow waves of ISP and ABP is capable of characterizing the spinal autoregulatory capacity. CONCLUSIONS: This preliminary observational study confirms morphological and spectral similarities between ISP in TSCI and ICP. Therefore, the known methods used for ICP waveform analysis could be transferred to ISP analysis and, upon verification, potentially used for monitoring TSCI patients.

Histopathology of the Retina from a Three Year-Old Suspected to Have Joubert Syndrome.

PURPOSE: To define the retinal pathology in a 3 year-old eye donor who died from complications of an undiagnosed genetic syndrome. METHODS: Eyes were fixed and analyzed using macroscopic fundus photography (MF), confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT). Small areas from the perifovea and periphery were processed for histology and indirect immunofluorescence, using antibodies specific to retinal proteins such as rhodopsin, cone arrestin, RPE65 and others. Available medical records were also reviewed. RESULTS: With all three imaging modalities, the affected donor's eyes lacked the distinct morphological detail typically observed with these techniques in postmortem control eyes. MF images showed a "photonegative effect" due to a hypopigmented macula relative to a hyperpigmented retinal background. cSLO imaging demonstrated a weak autofuorescence signal that was largely devoid of the usual retinal structures compared to the control. SD-OCT suggested disorganization of the affected retina, absence of a photoreceptor layer, and degeneration of the choroid in the macular area. Histologic findings indicated a highly disorganized photoreceptor layer in the macula and periphery. The RPE layer displayed thinning in some regions of the periphery and decreased pigmentation in most areas. Rods and cones were significantly reduced in the affected retina but a few cones were detected in the perifovea. Centrin-2 labeling was mostly absent from the connecting cilium of the photoreceptor cells. Medical record review pointed to a possible clinical diagnosis of Joubert syndrome. CONCLUSIONS: The retinal degenerative findings, and absence of centrin-2 labeling are compatible with the expected retinal phenotype in patients with Joubert syndrome.