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Understanding how feature learning affects generalization is among the foremost goals of modern deep learning theory. Here, we study how the ability to learn representations affects the generalization performance of a simple class of models: deep Bayesian linear neural networks trained on unstructured Gaussian data. By comparing deep random feature models to deep networks in which all layers are trained, we provide a detailed characterization of the interplay between width, depth, data density, and prior mismatch. We show that both models display sample-wise double-descent behavior in the presence of label noise. Random feature models can also display model-wise double-descent if there are narrow bottleneck layers, while deep networks do not show these divergences. Random feature models can have particular widths that are optimal for generalization at a given data density, while making neural networks as wide or as narrow as possible is always optimal. Moreover, we show that the leading-order correction to the kernel-limit learning curve cannot distinguish between random feature models and deep networks in which all layers are trained. Taken together, our findings begin to elucidate how architectural details affect generalization performance in this simple class of deep regression models., Comment: 35 pages, 7 figures. v2: minor typos corrected and references added; published in PRE

Decoding sensory stimuli from neural activity can provide insight into how the nervous system might interpret the physical environment, and facilitates the development of brain-machine interfaces. Nevertheless, the neural decoding problem remains a significant open challenge. Here, we present an efficient nonlinear decoding approach for inferring natural scene stimuli from the spiking activities of retinal ganglion cells (RGCs). Our approach uses neural networks to improve upon existing decoders in both accuracy and scalability. Trained and validated on real retinal spike data from > 1000 simultaneously recorded macaque RGC units, the decoder demonstrates the necessity of nonlinear computations for accurate decoding of the fine structures of visual stimuli. Specifically, high-pass spatial features of natural images can only be decoded using nonlinear techniques, while low-pass features can be extracted equally well by linear and nonlinear methods. Together, these results advance the state of the art in decoding natural stimuli from large populations of neurons.Author summaryNeural decoding is a fundamental problem in computational and statistical neuroscience. There is an enormous literature on this problem, applied to a wide variety of brain areas and nervous systems. Here we focus on the problem of decoding visual information from the retina. The bulk of previous work here has focused on simple linear decoders, applied to modest numbers of simultaneously recorded cells, to decode artificial stimuli. In contrast, here we develop a scalable nonlinear decoding method to decode natural images from the responses of over a thousand simultaneously recorded units, and show that this decoder significantly improves on the state of the art.

Viruses are obligate intracellular pathogens that utilize many of the host metabolic machineries for reproduction. Unlike the binary fission of bacteria, the replication process of viruses is more like a production line with a final assembly process to produce their progenies. Any agents used to prevent viral replication must be specific to the virus and cause as little problem for the host as possible. The rate of virus replication can also cause problems. In rapidly reproducing viruses, the high replication rate generates mutants that could be selected for resistance to antivirals. On the other hand, viruses could remain latent with little metabolic activity. None of the current antivirals are effective against latent viruses. The life cycle of a typical virus goes through the following stages: ● Attachment; ● Entry and uncoating; ● Replication of viral nucleic acid; ● Establishing latency or persistent infection (in some viruses); ● Translation of viral protein and post-translational modifications; ● Secretion and assembly of viral particles; and ● Release from host cells. Each of these steps can be used as antiviral targets. The most common strategy is to use a nucleoside analogue as a false substrate. However, such a false substrate can also be taken up by host polymerase and could result in toxicity, e.g. mitochondrial toxicity in some of the earlier antiretroviral drugs. The most successful example to circumvent this problem is aciclovir, which is the prodrug of the active agent aciclovir tri-phosphate. Aciclovir is a substrate for the viral enzyme thymidine kinase carried by the herpes simplex virus (HSV) and varicella-zoster virus (VZV), which converts it into aciclovir monophosphate. As this only happens inside cells infected by HSV or VZV, it is concentrated only in infected cells. Host enzymes then add further phosphates to form the active agent aciclovir triphosphate, which has a higher affinity to viral polymerase than host polymerase. It acts as a false substrate for the viral polymerase and results in premature termination of nucleic acid replication. A similar mechanism is utilized in ganciclovir against cytomegalovirus (CMV). The viral phosphate kinase involved in the case of CMV is the UL97 protein.

These are diseases in which an effective preventive vaccine exists. A death that could have been prevented by vaccination is a vaccine- preventable death. The World Health Organization (WHO) has identified twenty-five diseases as vaccine preventable. This list may expand as new vaccines are being developed. The Expanded Programme on Immunization, or EPI, is vaccination programme introduced in 1974 by the WHO to all nations. The EPI initially targeted diphtheria, whooping cough, tetanus, measles, poliomyelitis, and tuberculosis. The aim was to provide universal immunization for all children by 1990 and to achieve health for all by 2000. In 2010, about 85% of children under one year of age in the world had received at least three doses of DTP vaccine (diphtheria, tetanus, and polio). Additional vaccines have now been added to the original six targets. Most countries have now added Hepatitis B (not in UK) and Haemophilus influenzae type b (Hib) to their routine infant immunization schedules, and an increasing number are in the process of adding pneumococcal conjugate vaccine and rotavirus vaccines to their schedules. Immunization is a proven tool for controlling and even eradicating infectious diseases. The immunization campaign against smallpox between 1967 and 1977 resulted in the eradication of smallpox. Apart from smallpox, the only other viral infection that was declared eradicated through vaccination campaign was rinderpest in cattle (2011), a close relative of measles virus in humans. Another major infection target for global eradication is against poliomyelitis—the global polio eradication initiative (GPEI). When the programme began in 1988, polio threatened 60% of the world’s population. Eradication of poliomyelitis is now within reach: infections have fallen by 99%; wild type polio type 2 was last detected in 1999 and declared eradicated in 2015; wild-type poliovirus type 3 has not been detected in the world since 2012. Poliovirus type 1 is the only wild- type virus in circulation and endemic transmission is only reported in Afghanistan and Pakistan. Currently, the old trivalent oral poliovirus vaccine is replaced by the more potent bivalent poliovirus type 1 and 3 vaccine. Many western countries have switched from oral vaccine to the injected inactivated vaccine to avoid the problem of vaccine- induced paralysis, which could be associated with the oral live attenuated vaccine.

Urethritis, characterized by inflammation of the urethra in men, is caused by Neisseria gonorrhoeae (gonococcus), Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. Other causes of non-gonococcal urethritis include ureaplasmas, adenoviruses, and herpes simplex viruses. The presence of urethritis is confirmed by the presence of five or more polymorphs in urethral smear by high-power microscopy. Symptoms can be minor to profound and vary from clear to mucopurulent discharge. Gonococcus is commoner in men who have sex with men (MSM) compared to heterosexuals, and high-risk activities such as chemsex parties increase spread with significant public health consequences. Antibiotic resistance in gonococcus has clinical and public health implications as three cases of extensively drug-resistant Neisseria gonorrhoeae with resistance to ceftriaxone (MIC = 0.5 mg/L) and high-level resistance to azithromycin (MIC > 256 mg/L) have been described compromising current treatment recommended by British Association for Sexual Health and HIV Guidelines (BASHH). In England an outbreak of high level azithromycin-resistant gonococcus has also been described by Public Health England (PHE), who alerted clinicians about the need for follow up and test of cure, contact tracing, and treatment failure. C. trachomatis infection can be treated with azithromycin 1g orally as a single dose or with seven days of oral doxycycline. Risk factors for chlamydia include age younger than twenty-five years, multiple sexual partners, and avoidance of barrier methods for contraception. Metronidazole 2g single dose or 400– 500mg twice daily for seven days is recommended for treatment of trichomonas, which can cause a moderate discharge in up to 60% of males. Resistance to azithromycin and doxycycline is common in M. genitalium strains and management of these patients with urethritis requires GUM referral for comprehensive investigation, contact tracing, and public health notification. Molecular methods are used for the diagnosis of these organisms and gonococcal culture is undertaken to obtain antimicrobial susceptibility data from patients with a previous diagnosis by molecular method, in GUM attendees, and their contacts. Herpes simplex infection results in a painful ulcer preceded by a vesicle. The diagnosis can be confirmed using polymerase chain reaction (PCR) tests of a swab taken from the vesicle or ulcer.

Blood- borne viruses (BBVs) are viral infections transmitted by blood or body fluid. In practice, any viral infection that achieves a high viral load in blood or body fluid can be transmitted through exposure to infected biological materials. In western countries, the most significant BBVs are human immunodeficiency viruses (HIV1 and HIV2), hepatitis B virus (HBV) and hepatitis C virus (HCV). Other viruses that can be transmitted by blood and body fluid include human T cell lymphotropic viruses (HTLV1 and HTLV2), cytomegalovirus, West Nile virus and viruses responsible for viral haemorrhagic fever such as Ebola virus, Lassa virus, and Crimean-Congo haemorrhagic fever virus. BBVs are transmitted via exposure to blood and body fluid. Some examples of routes of transmission include: ● Sharing needles in people who inject drugs (PWID); ● Medical re-use of contaminated instruments (common in resource poor settings); ● Sharps injuries in healthcare setting, including in laboratories (less commonly through mucosal exposure); ● Transfusion of blood contaminated with BBVs (failure to screen blood donors); ● Transplantation of organs from BBV-infected donors; ● Sexual exposure to BBV-infected body fluid; and ● Exposure to maternal BBV infection: intrauterine, perinatally, or postnatally. If exposure to a BBV is via a needle stick injury in a healthcare setting, immediate first aid needs to be carried out by gently encouraging bleeding and washing the exposed area with soap and water. Prompt reporting of the incident is required so that an assessment can be done as soon as possible to determine if post-exposure prophylaxis (PEP) is required. The decision may be aided by urgent assessment of source patient infection status. The British Medical Association has issued guidance for testing adults who lack the capacity to consent. In the case of a sexual exposure to a BBV, immediate consultation to a genito-urinary medicine (GUM) clinic is warranted. The risk of transmission of BBVs associated with exposure depends on the nature of the exposure and the body fluid involved. The following factors are important in needle stick injuries: ● Deep percutaneous injury. ● Freshly used sharps. ● Visible blood on sharps.

Post-exposure prophylaxis (PEP) is a treatment administered to an individual to prevent the development of infection or reduce the severity of illness after a potential or documented exposure to a microorganism. This may primarily be for the protection of the exposed individual concern, or in the case of a pregnant woman, for protecting the foetus in utero. PEP may also be useful in public health to reduce the risk of secondary spread of infection. A good history is required in order to make a proper assessment of the risk. The following questions should be asked: A. Which infection is suspected and is the source infectious? It is straight forward if the diagnosis of the source of exposure is already known, e.g. known HIV, established diagnosis of tuberculosis. However, in many cases, the diagnosis of the source may not be certain, e.g. needle stick injury involving a needle of unknown origin, bitten by a stray dog, exposed to a child with a non-specific rash. In such cases, a risk assessment is required to assess the likelihood that the source may be infectious. Knowledge of local epidemiology or recent outbreaks in a particular locality may help in such risk assessment. B. What is the nature of the exposure? Knowledge of the mode of transmission of a microorganism is important to establish if there is any risk of transmission through the exposure In the case of mother-to-child transmission, PEP to the neonate born to a mother with an infection is effective if the mode of transmission is predominately perinatal, e.g. hepatitis B. If the mode of transmission is transplacental, it is too late to administer PEP to the baby after delivery. Instead, the expected mother should be given prophylaxis during pregnancy to prevent infection, e.g. chicken pox, or given antivirals to reduce infectivity, e.g. maternal hepatitis B with a high viral load when transplacental infection may occur. In HIV, where transmission can occur both transplacentally and perinatally, antiretroviral therapy (ART) needs to be given during pregnancy and often during labour as well as to the baby after birth.

In order to be classified as a virus, certain criteria have to be fulfilled. Viruses must ● Be only capable of growth and multiplication within living cells, i.e. obligate intracellular parasite. Host cells could include humans, animals, insects, plants, protozoa, or even bacteria. ● Have a nucleic acid genome (either RNA or DNA, but not both) surrounded by a protein coat (capsid). ● Have no semipermeable membrane, though some have an envelope formed of phospholipids and proteins. ● Be inert outside of the host cell. Enveloped viruses are susceptible to inactivation by organic solvents such as alcohol. ● Perform replication by independent synthesis of components followed by assembly (c.f. binary fission in bacteria). Viruses are considered as a bundle of genetic programmes encoded in nucleic acids and packaged with a capsid +/ - envelope protein, which can be activated on entry into a host cell (compare this with computer viruses packaged in an enticing way in order to infect and take over control of your PC). Although they share some similarities in their properties, mycoplasma and chlamydia are true bacteria. The virion (assembled infectious particle) consists of viral nucleic acid and capsid. The nucleic acid of a virus can either be ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and the amount of genetic material varies widely, with some viruses able to encode a few proteins and others having genetic material that encodes hundreds of proteins. In association with the nucleic acid there may be non- structural viral proteins, such as a viral polymerase. The nucleic acid and non- structural proteins are protected by a surrounding layer of capsid proteins. The capsid includes proteins which can attach to host cell receptors. The proteins and the cell receptors to which they bind determine a virus’ tropism, i.e., the ability to bind to and enter different cell types. The term nucleocapsid refers to the nucleic acid core surrounded by capsid protein. Some viruses also have an envelope made up of phospholipids and proteins surrounding the nucleocapsid. This envelope can be formed by the host cell membrane during the process of a virus budding from a cell during replication.

In the majority of UK laboratories initial testing for HIV is now performed using a fourth generation test, which is a combination test for antibody to HIV and p24 antigen. These tests should be able to detect antibody to both HIV-1 and HIV-2. In addition, due to the heterogeneity of the virus they should be able to reliably detect antibody to the main circulating subtypes of HIV-1, i.e. group M (Major), O (Outlier), and N (non-M, non-O). The p24 antigen is an HIV capsid protein which is produced in large quantities during initial infection, prior to seroconversion. The sensitivity and specificity of fourth generation tests is typically > 99%. However, all positive results need further confirmation tests, as discussed below. Third generation laboratory assays only test for the presence of antibody to HIV. Though it includes the detection of IgM (which is not included in second generation assays), they do not detect early infection with isolated HIV antigen prior to seroconversion. Point-of-care testing for HIV is performed in the clinic or at bedside. Like laboratory based assays these tests can be either third or fourth generation. The sensitivity and specificity of point-of-care tests is considered lower than that of laboratory tests, and all positive results require confirmation with a laboratory assay. The window period is the length of time following infection with HIV until the appearance of laboratory markers of HIV infection in the blood. This period varies depending on which marker, i.e. antibody or antigen, is being tested for. The window period for fourth-generation tests is between eleven days and one month. Patients being counselled prior to this testing should be advised that a negative result does not cover risk exposures in the preceding month. These patients should be advised to have repeat testing if they have any further exposure risks in the preceding month prior to testing. For third-generation tests the window period is up to three months, correlating with the amount of time it may take for antibodies to HIV to develop.

The gastro-intestinal tract (GIT) hosts the most numerous and diverse reservoir of microbes in humans. There is increasing interest in the relationship between the GIT microbiome and human health. Obesity, diabetes, allergy, and a number of inflammatory diseases have been linked with the human GIT microbiome. Infections of the GIT arise either as a result of a change in the relationship between the commensal microbes colonizing the GIT (endogenous infection) or entry in to the GIT of a micro-organism which causes disease (exogenous infection). Commensals most commonly invade host tissues as a result of compromised defensive barriers. Disease associated with exogenous infection can be toxin-mediated, or associated with local or systemic invasion of the host. Endogenous infections are usually polymicrobial. In the mouth the aetiology, presentation, and anatomical associations have led to the description of a number of syndromes. Peritonsillar infection with involvement of the internal jugular vein is Lemierre’s syndrome, which is particularly associated with infection with Fusobacterium necrophorum. ‘Trench mouth’ is a severe form of ulcerative gingivitis, so named because in the absence of oral hygiene it was a relatively common diagnosis among those in the trenches during the First World War. Ludwig’s angina is a severe infection of the floor of the mouth which spreads in to the submandibular and sub-lingual space, often following a tooth-related infection. Deep neck infections are more common in children than adults and can involve the parapharyngeal, retropharyngeal, peri-tonsillar, or sub-mandibular spaces. Children with deep neck infections are more likely than adults to present with cough and respiratory distress. Oesophagitis has a wide range of potential aetiologies. Fungi (particularly Candida species) are probably the most common microbial cause of oesophagitis. Fungal infection of the distal oesophagus is thought to play an important role in the pathogenesis of disseminated fungal infection. Risk factors for fungal infection include poor oral intake, exposure to antibiotics, immunocompromise (HIV, steroids, cancer treatments), gastric acid suppressants, and damage to mucosal integrity (naso-gastric tubes, acid reflux, varices). Bacteria (including Mycobacteria, Actinomycetes, Treponemes), parasites, and viruses (herpes simplex, cytomegalovirus) are rarer infectious causes of oesophagitis.

The Control of Substances Hazardous to Health Regulations 2002 (COSHH) classifies biological agents into four categories (Hazard Groups) according to an approved list by the Health and Safety Executive (HSE). Biological agents are bacteria, viruses, parasites, and fungi that can cause harm to human health, usually due to infection, although some are toxic or can cause an allergy. The approved list is relevant to risk assessment for work with biological agents and the application of appropriate control measures. Hazard Group 1 agents are not considered to pose a risk to human health, while Hazard Group 4 agents present the greatest risk. The principle of the categorization is laid down by the Advisory Committee on Dangerous Pathogens (ACDP) based on the following (see also Table 13.1): ● the likelihood that it will cause disease by infection or toxicity in humans; ● how likely it is that the infection would spread to the community; and ● the availability of any prophylaxis or treatment. The ACDP only considers the risks to human health when deciding appropriate classification. Some listed agents can also cause disease in animals (zoonoses) and have also been assigned a hazard classification under the Specified Animal Pathogens Order (SAPO). In allocating human pathogens to a hazard group, no account is taken of particular effects on those whose susceptibility to infection may be affected, for example, because of pre-existing disease, medication, compromised immunity, pregnancy, or breastfeeding. Type 2 polio virus has been reclassified from Hazard Group 2 to Hazard Group 3 to bring the UK in line with the expectations of World Health Organization’s global polio eradication programme. This reclassification also applies to attenuated type 2 polio viruses once this component is no longer used as part of the trivalent polio vaccine. Zika virus has been reclassified from Hazard Group 3 to Hazard Group 2 as there is substantial evidence that while it can cause human disease, this is generally mild. It is also unlikely to spread to the community from the laboratory. COSHH regulations specify four containment levels for activities which involve working with biological agents.

An exanthem (or exanthema) is a widespread skin rash accompanying a disease or fever. It usually occurs in children as part of a common systemic childhood viral infection, but can also occur in adults and can be caused by bacterial infections, toxin or drug reactions. An enanthem (or enanthema) is a rash that occurs in the mucous membrane, typically in the mouth, as the result of the same disease process of an exanthema. Because the presence of a rash is a very striking feature, historically, several of the commonly seen febrile illnesses associated with rash have been recognized and named in numerical order. There are various things to look out for when assessing a patient with exanthema. These can include the type and evolution of the rash, as well as contact, vaccine, drug, sexual, and travel history. ● Type of rash: ■ maculopapular; ■ vesicular; ■ petechial. ● Evolution of the rash: ■ prodrome, if any; ■ date of onset of fever; ■ date of onset of the rash; ■ progression of the rash (e.g. starting location and spread); ■ other associated features (e.g. conjunctivitis, lymphadenopathy, hepatosplenomegaly). ● Contact history: ■ history of contact with anyone with febrile or rash illness; ■ recent local outbreaks, if any; ■ contact with other vulnerable individuals before and after onset of illness (for infection control purposes). ● Vaccine history: ■ recent history of any vaccination; ■ previous vaccination history (particularly MMR and varicella); ■ timing of these vaccines and number of doses. ● Drug history: ■ including antibiotics given for the illness. ● Sexual history: ■ always consider this in any patient. ● Recent travel history: ■ record timing and location; ■ history of insect bites. A good description of the rash can help in narrowing down the possible causes. The commonly seen rashes can be maculopapular, vesicular, or petechial. Maculopapular rash can be further categorized into subtypes. These include: ● morbilliform—a red rash which is measles-like, two to ten mm in diameter, and which merge to form confluent patches.

BackgroundTechnological interventions such as mobile apps, Web-based social networks, and wearable trackers have the potential to influence physical activity; yet, only a few studies have examined the efficacy of an intervention bundle combining these different technologies. ObjectiveThis study aimed to pilot test an intervention composed of a social networking mobile app, connected with a wearable tracker, and investigate its efficacy in improving physical activity, as well as explore participant engagement and the usability of the app. MethodsThis was a pre-post quasi-experimental study with 1 arm, where participants were subjected to the intervention for a 6-month period. The primary outcome measure was the difference in daily step count between baseline and 6 months. Secondary outcome measures included engagement with the intervention and system usability. Descriptive and inferential statistical tests were conducted; posthoc subgroup analyses were carried out for participants with different levels of steps at baseline, app usage, and social features usage. ResultsA total of 55 participants were enrolled in the study; the mean age was 23.6 years and 28 (51%) were female. There was a nonstatistically significant increase in the average daily step count between baseline and 6 months (mean change=14.5 steps/day, P=.98, 95% CI –1136.5 to 1107.5). Subgroup analysis comparing the higher and lower physical activity groups at baseline showed that the latter had a statistically significantly higher increase in their daily step count (group difference in mean change from baseline to 6 months=3025 steps per day, P=.008, 95% CI 837.9-5211.8). At 6 months, the retention rate was 82% (45/55); app usage decreased over time. The mean system usability score was 60.1 (SD 19.2). ConclusionsThis study showed the preliminary efficacy of a mobile social networking intervention, integrated with a wearable tracker to promote physical activity, particularly for less physically active subgroups of the population. Future research should explore how to address challenges faced by physically inactive people to provide tailored advices. In addition, users’ perspectives should be explored to shed light on factors that might influence their engagement with the intervention.

This paper will present a concept to use matermaterial thin film deposited on a window glass to absorb tuned solar spectrum for anti-frost/anti-fog and energy-saving in cold weather, meanwhile the luminous transmittance of the windows can be maintained. In warmer weather, the opposite side of a rotatable window can be turned to face the sunlight to reflect the sunlight away with the perfect mirror function of the base ground layer of the metamaterial thin film. By adjusting base ground coating structure, perfect or non-perfect mirror can be formed for natural solar reflection or transmittance. The metal-dielectric-metal nano-scale metamaterial structures with periodic metal-dielectric interfaces, when shined with light, acquire surface plasmons thus trapping light at subwavelength scales. When the metamaterial film is coated on the outside of a glass window, it will lead to efficient solar radiation absorption, which can be used for anti-frost/anti-fog and energy-saving windows of transportation vehicles ...

BACKGROUND Technological interventions such as mobile apps, Web-based social networks, and wearable trackers have the potential to influence physical activity; yet, only a few studies have examined the efficacy of an intervention bundle combining these different technologies. OBJECTIVE This study aimed to pilot test an intervention composed of a social networking mobile app, connected with a wearable tracker, and investigate its efficacy in improving physical activity, as well as explore participant engagement and the usability of the app. METHODS This was a pre-post quasi-experimental study with 1 arm, where participants were subjected to the intervention for a 6-month period. The primary outcome measure was the difference in daily step count between baseline and 6 months. Secondary outcome measures included engagement with the intervention and system usability. Descriptive and inferential statistical tests were conducted; posthoc subgroup analyses were carried out for participants with different levels of steps at baseline, app usage, and social features usage. RESULTS A total of 55 participants were enrolled in the study; the mean age was 23.6 years and 28 (51%) were female. There was a nonstatistically significant increase in the average daily step count between baseline and 6 months (mean change=14.5 steps/day, P=.98, 95% CI –1136.5 to 1107.5). Subgroup analysis comparing the higher and lower physical activity groups at baseline showed that the latter had a statistically significantly higher increase in their daily step count (group difference in mean change from baseline to 6 months=3025 steps per day, P=.008, 95% CI 837.9-5211.8). At 6 months, the retention rate was 82% (45/55); app usage decreased over time. The mean system usability score was 60.1 (SD 19.2). CONCLUSIONS This study showed the preliminary efficacy of a mobile social networking intervention, integrated with a wearable tracker to promote physical activity, particularly for less physically active subgroups of the population. Future research should explore how to address challenges faced by physically inactive people to provide tailored advices. In addition, users’ perspectives should be explored to shed light on factors that might influence their engagement with the intervention.

The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker.The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset.The initial analysis of genome sequences detected substantial hidden variability in the London HIV epidemic. Analysing full genome sequences, as opposed to only PR+RT, identified previously undetected recombinants. It provided a more reliable description of CRFs (that would be otherwise misclassified) and transmission clusters.

We derive the equations of motion for the planar somersault, which consist of two additive terms. The first is the dynamic phase that is proportional to the angular momentum, and the second is the geometric phase that is independent of angular momentum and depends solely on the details of the shape change. Next, we import digitised footage of an elite athlete performing 3.5 forward somersaults off the 3m springboard, and use the data to validate our model. We show that reversing and reordering certain sections of the digitised dive can maximise the geometric phase without affecting the dynamic phase, thereby increasing the overall rotation achieved. Finally, we propose a theoretical planar somersault consisting of four shape changing states, where the optimisation lies in finding the shape change strategy that maximises the overall rotation of the dive. This is achieved by balancing the rotational contributions from the dynamic and geometric phases, in which we show the geometric phase plays a small but important role in the optimisation process., Comment: 21 pages, 14 figures, work from PhD thesis of William Tong

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated versionTong, C. Y. W., et al. (2015). "Deep Sequencing of HIV-1 in Cerebrospinal Fluid." Clinical Infectious Diseases 61(6): 1022-1025. is available online at: http://cid.oxfordjournals.org/content/61/6/1022.full.pdf+html

Background & methods The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data. The pipeline was applied to 420 HIV samples collected at University College London Hospitals NHS Trust and Barts Health NHS Trust (London) and sequenced using an Illumina MiSeq at the Wellcome Trust Sanger Institute (Cambridge). Consensus genomes were generated and subtyped using COMET, and unique recombinants were studied with jpHMM and SimPlot. Maximum-likelihood phylogenetic trees were constructed using RAxML to identify transmission networks using the Cluster Picker. Results The pipeline generated sequences of at least 1Kb of length (median = 7.46Kb, IQR = 4.01Kb) for 375 out of the 420 samples (89%), with 174 (46.4%) being NFLG. A total of 365 sequences (169 of them NFLG) corresponded to unique subjects and were included in the down-stream analyses. The most frequent HIV subtypes were B (n = 149, 40.8%) and C (n = 77, 21.1%) and the circulating recombinant form CRF02_AG (n = 32, 8.8%). We found 14 different CRFs (n = 66, 18.1%) and multiple URFs (n = 32, 8.8%) that involved recombination between 12 different subtypes/CRFs. The most frequent URFs were B/CRF01_AE (4 cases) and A1/D, B/C, and B/CRF02_AG (3 cases each). Most URFs (19/26, 73%) lacked breakpoints in the PR+RT pol region, rendering them undetectable if only that was sequenced. Twelve (37.5%) of the URFs could have emerged within the UK, whereas the rest were probably imported from sub-Saharan Africa, South East Asia and South America. For 2 URFs we found highly similar pol sequences circulating in the UK. We detected 31 phylogenetic clusters using the full dataset: 25 pairs (mostly subtypes B and C), 4 triplets and 2 quadruplets. Some of these were not consistent across different genes due to inter- and intra-subtype recombination. Clusters involved 70 sequences, 19.2% of the dataset. Conclusions The initial analysis of genome sequences detected substantial hidden variability in the London HIV epidemic. Analysing full genome sequences, as opposed to only PR+RT, identified previously undetected recombinants. It provided a more reliable description of CRFs (that would be otherwise misclassified) and transmission clusters.

Summary Objectives : To re-assess the prevalence and patient characteristics of hepatitis D virus (HDV) infection among hepatitis B patients in inner city London. Methods : All hepatitis B patients attending clinics over a 52 months period were tested for HDV antibody. All reactive samples were also tested for anti-HDV IgM and RNA. The characteristics of HDV seronegative patients first seen in the calendar year 2008 were compared with all HDV seropositive patients in the cohort. Results : Of 1048 hepatitis B patients, 11 had equivocal anti-HDV serology (1%) and 22 were HDV seropositive (2.1%, 95%CI 1.39–3.16%); 12 were anti-HDV IgM positive and 15 HDV RNA positive. No patient with equivocal anti-HDV serology had detectable HDV RNA. Five HDV seropositive patients were intravenous drug users (22.7%); 17/22 were from abroad with 11/22 (50%) from sub-Saharan Africa. HDV seropositive patients had poorer laboratory parameters and were more likely to have evidence of cirrhosis. Triple infected (HIV/HBV/HDV) patients were also more likely to have cirrhosis than HIV/HBV dually infected patients. Conclusions : The prevalence of HDV in hepatitis B patients in inner city London was about 2%. The role of migration from endemic countries should be recognised.

Aim To assess the role of imaging in the early management of encephalitis and the agreement on findings in a well-defined cohort of suspected encephalitis cases enrolled in the Prospective Aetiological Study of Encephalitis conducted by the Health Protection Agency (now incorporated into Public Health England). Materials and methods Eighty-five CT examinations from 68 patients and 101 MRI examinations from 80 patients with suspected encephalitis were independently rated by three neuroradiologists blinded to patient and clinical details. The level of agreement on the interpretation of images was measured using the kappa statistic. The sensitivity, specificity, and negative and positive predictive values of CT and MRI for herpes simplex virus (HSV) encephalitis and acute disseminated encephalomyelitis (ADEM) were estimated. Results The kappa value for interobserver agreement on rating the scans as normal or abnormal was good (0.65) for CT and moderate (0.59) for MRI. Agreement for HSV encephalitis was very good for CT (0.87) and MRI (0.82), but only fair for ADEM (0.32 CT; 0.31 MRI). Similarly, the overall sensitivity of imaging for HSV encephalitis was ∼80% for both CT and MRI, whereas for ADEM it was 0% for CT and 20% for MRI. MRI specificity for HSV encephalitis between 3–10 days after symptom onset was 100%. Conclusion There is a subjective component to scan interpretation that can have important implications for the clinical management of encephalitis cases. Neuroradiologists were good at diagnosing HSV encephalitis; however, agreement was worse for ADEM and other alternative aetiologies. Findings highlight the importance of a comprehensive and multidisciplinary approach to diagnosing the cause of encephalitis that takes into account individual clinical, microbiological, and radiological features of each patient., Highlights • We assessed the role of imaging in encephalitis. • We assessed the agreement between raters on scan interpretation. • Diagnosis for herpes simplex encephalitis (HSE) was good. • Agreement was worse for ADEM and other alternative aetiologies. • HSE can be dismissed if MRI normal 72 hours after neurological symptom onset (with negative CSF tests).

Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences ( n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. We estimated that the common ancestor of human EV-71 likely emerged around 1941 (95% confidence interval [CI], 1929 to 1952), subsequently diverging into three genogroups: B, C, and the now extinct genogroup A. Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations. Estimated phylogenies showed a complex pattern of spatial structure within well-sampled subgenogroups, suggesting endemicity with occasional lineage migration among locations, such that past HFMD epidemics are unlikely to be linked to continuous transmission of a single strain of virus. In addition, rises in genetic diversity are correlated with the onset of epidemics, driven in part by the emergence of novel EV-71 subgenogroups. Using subgenogroup C1 as a model, we observe temporal strain replacement through time, and we investigate the evidence for positive selection at VP1 immunogenic sites. We discuss the consequences of the evolutionary dynamics of EV-71 for vaccine design and compare its phylodynamic behavior with that of influenza virus.

We present the mathematical framework of an athlete modelled as a system of coupled rigid bodies to simulate platform and springboard diving. Euler's equations of motion are generalised to non-rigid bodies, and are then used to innovate a new dive sequence that in principle can be performed by real world athletes. We begin by assuming shape changes are instantaneous so that the equations of motion simplify enough to be solved analytically, and then use this insight to present a new dive (513XD) consisting of 1.5 somersaults and 5 twists using realistic shape changes. Finally, we demonstrate the phenomenon of converting pure somersaulting motion into pure twisting motion by using a sequence of impulsive shape changes, which may have applications in other fields such as space aeronautics., Comment: 26 pages, 17 figures, work from PhD thesis of William Tong

There is little research on exceptional events and crime. Yet exceptional events, such as natural disasters, worldwide political meetings, and international sporting competitions, affect the lifestyles and routines of large numbers of people. In this article, we examine the impact of the 2010 Winter Olympic Games on assault, theft, mischief, and prostitution in Vancouver neighbourhoods. Overall, there is no evidence to support the claim that the Olympic Games affected all crime types and in all places. However, we do find increases in assault that relate to the Olympic Games in a few key neighbourhoods. As with previous research, it appears that the substantial increase in the number of security personnel (police, military, etc.) mitigated the potential increase in crime.