Decision-Making Time Cells in Hippocampal Dorsal CA1.

Sequential neural dynamics encoded by "time cells" play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+ imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.

A robust method for approximate visual robot localization in feature-sparse sewer pipes.

Buried sewer pipe networks present many challenges for robot localization systems, which require non-standard solutions due to the unique nature of these environments: they cannot receive signals from global positioning systems (GPS) and can also lack visual features necessary for standard visual odometry algorithms. In this paper, we exploit the fact that pipe joints are equally spaced and develop a robot localization method based on pipe joint detection that operates in one degree-of-freedom along the pipe length. Pipe joints are detected in visual images from an on-board forward facing (electro-optical) camera using a bag-of-keypoints visual categorization algorithm, which is trained offline by unsupervised learning from images of sewer pipe joints. We augment the pipe joint detection algorithm with drift correction using vision-based manhole recognition. We evaluated the approach using real-world data recorded from three sewer pipes (of lengths 30, 50 and 90 m) and benchmarked against a standard method for visual odometry (ORB-SLAM3), which demonstrated that our proposed method operates more robustly and accurately in these feature-sparse pipes: ORB-SLAM3 completely failed on one tested pipe due to a lack of visual features and gave a mean absolute error in localization of approximately 12%-20% on the other pipes (and regularly lost track of features, having to re-initialize multiple times), whilst our method worked successfully on all tested pipes and gave a mean absolute error in localization of approximately 2%-4%. In summary, our results highlight an important trade-off between modern visual odometry algorithms that have potentially high precision and estimate full six degree-of-freedom pose but are potentially fragile in feature sparse pipes, versus simpler, approximate localization methods that operate in one degree-of-freedom along the pipe length that are more robust and can lead to substantial improvements in accuracy.

Country differences and determinants of yield in programmatic migrant TB screening in four European countries.

INTRODUCTION The WHO End TB Strategy emphasises early diagnosis and screening of TB in high-risk groups, including migrants. We analysed TB yield data from four large migrant TB screening programmes to inform TB policy.METHODS We pooled routinely collected individual TB screening episode data from Italy, the Netherlands, Sweden and the United Kingdom under the European Union Commission E-DETECT.TB grant, described characteristics of the screened population, and analysed TB case yield.RESULTS We collected data on 2,302,260 screening episodes among 2,107,016 migrants, mostly young adults aged 18-44 years (77.8%) from Asia (78%) and Africa (18%). There were 1,658 TB cases detected through screening, with substantial yield variation (per 100,000): 201.1 for Sweden (95% confidence intervals CI 111.4-362.7), 68.9 (95% CI 65.4-72.7) for the United Kingdom, 83.2 (95% CI 73.3-94.4) for the Netherlands and 653.6 (95% CI 445.4-958.2) in Italy. Most TB cases were notified among migrants from Asia (n = 1,206, 75/100,000) or Africa (n = 370, 76.4/100,000), and among asylum seekers (n = 174, 131.5/100,000), migrants to the Netherlands (n = 101, 61.9/100,000) and settlement visa migrants to the United Kingdom (n = 590, 120.3/100,000).CONCLUSIONS We found considerable variations in yield across programmes, types of migrants and country of origin. These variations may be partly explained by differences in migration patterns and programmatic characteristics.

Public health outcome of Tuberculosis Cluster Investigations, England 2010-2013.

OBJECTIVES: Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB strain-typed (ST) clusters. METHODS: A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. RESULTS: There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. CONCLUSIONS: We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting.

In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons.

Anesthetic doses of ketamine induce apoptosis, as well as gene expression of activity-dependent neuroprotective protein (ADNP), a putative homeodomain transcription factor in rat pups (P7). This study investigated if ketamine induced ADNP protein in a dose-dependent manner in vitro and in vivo using primary cultures of cortical neurons and neonatal pups (P7). In vivo immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased ADNP in the somatosensory cortex (SCC) which was previously identified to be damaged by repeated exposure to anesthetic doses of ketamine. Administration of low-dose ketamine prior to full sedation prevented caspase-3 activation in the hippocampus and SCC. Primary cultures of cortical neurons treated with ketamine (10 µM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones. Furthermore, neuronal production and localization of ADNP varied as a function of both ketamine concentration and length of exposure. Taken together, these data support the model that ADNP induction may be partially responsible for the efficacy of a low-dose ketamine pre-treatment in preventing ketamine-induced neuronal cell death.

Midwives' influenza vaccine uptake and their views on vaccination of pregnant women.

BACKGROUND: Pregnant women in England are now offered seasonal influenza vaccine. Midwives could be influential in promoting this, but specific information on their views on the policy and their role in its implementation is lacking. METHODS: London midwives were surveyed for their views on the new policy and their own vaccine uptake, using an anonymously self-completed semi-structured online survey via a convenience sampling approach. RESULTS: In total, 266 midwives responded. Sixty-nine percent agreed with the policy of vaccinating all pregnant women. Seventy-six percent agreed that midwives should routinely advise pregnant women on vaccination, but only 25% felt adequately prepared for this role. Just 28% wished to be vaccinators, due to concerns about increased workload and inadequate training. Forty-three percent received seasonal influenza vaccine themselves. Major reasons for non-uptake were doubts about vaccine necessity (34%), safety (25%) and effectiveness (10%); and poor arrangements for vaccination (11%). Suggested strategies for improving their own uptake included better access to evidence of effectiveness (67%) and improved work-based vaccination (45%). CONCLUSIONS: London midwives support influenza vaccination of pregnant women, but are more willing to give advice on, than to administer, the vaccine. Midwives' own influenza vaccine uptake could improve with more information and easier access to vaccination in their workplace.

The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Clostridium perfringens in London, July 2009: two weddings and an outbreak.

Food poisoning outbreaks caused by Clostridium perfringens enterotoxin occur occasionally in Europe but have become less common in recent years. This paper presents the microbiological and epidemiological results of a large C. perfringens outbreak occurring simultaneously at two weddings that used the same caterer. The outbreak involved several London locations and required coordination across multiple agencies. A case-control study (n=134) was carried out to analyse possible associations between the food consumed and becoming ill. Food, environmental and stool samples were tested for common causative agents, including enterotoxigenic C. perfringens. The clinical presentation and the epidemiological findings were compatible with C. perfringens food poisoning and C. perfringens enterotoxin was detected in stool samples from two cases. The case-control study found statistically significant associations between becoming ill and eating either a specific chicken or lamb dish prepared by the same food handler of the implicated catering company. A rapid outbreak investigation with preliminary real-time results and the successful collaboration between the agencies and the caterer led to timely identification and rectification of the failures in the food handling practices.

Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges--updated 10 February 2004.

Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.

Selective production of rat mutant selenoprotein W with and without bound glutathione.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and electrospray ionization mass spectrometry (ESI MS) analysis of a 6x His-tagged recombinant form of rat mutant selenoprotein W (RMSW) reveals that aerobic growth conditions primarily produce a form of RMSW without bound glutathione (10,305 Da) whereas anaerobic conditions produce a glutathione-bound (305 Da) form (10,610 Da). Purification of RMSW was achieved with a procedure employing acetone precipitation and DEAE-cellulose chromatography, in addition to Ni-NTA agarose chromatography. Additional steps, including polyvalent metal ion binding (PMIB) resin chromatography and CM-cellulose chromatography, were necessary after elution from the Ni-NTA agarose column, in order to maintain solubility of the purified protein.

Surveillance of antenatal infections--HIV, hepatitis B, syphilis and rubella susceptibility in London.

London has relatively high rates of HIV, hepatitis B and syphilis, and has the potential for undiagnosed infection in pregnancy. As part of a drive to improve HIV testing in pregnancy, surveillance of a number of antenatal infections has been carried out in London's 30 maternity units since 2000. Infection screening rates rose from 89% in 2000 to 94% in 2002, and HIV screening rates increased from 66% to 86%. During 2002, 115,230 women booked for antenatal care; 998 were HBsAg positive (about ten in 1000), 452 were HIV positive (five in 1,000), 412 tested positive for syphilis (four in 1000), and 3,929 were susceptible to rubella (36 in 1000). The main burden of infection was concentrated in a few geographic areas. Worryingly the majority of women found to be HIV positive were diagnosed by antenatal screening and not before.

Dityrosine as a product of oxidative stress and fluorescent probe.

Dityrosine can be a natural component of protein structure, a product of environmental stress, or a product of in vitro protein modification. It is both a cross-link and a fluorescent probe that reports structural and functional information on the cross-linked protein molecule. Diverse reactions produce tyrosyl radicals, which in turn may couple to yield dityrosine. Identification and quantitation of dityrosine in protein hydrolysates usually employs reversed phase high pressure liquid chromatography (RP-HPLC) or gas chromatography. RP-HPLC of protein hydrolysates that have been derivatized with dabsyl chloride gives a complete amino acid analysis that includes dityrosine and 3-nitrotyrosine. Calmodulin, which contains a single pair of tyrosyl residues, undergoes both photoactivated and enzyme-catalyzed dityrosine formation. Polarization measurements, employing the intrinsic fluorescence of dityrosine, and catalytic activity determinations show how different patterns of inter- and intramolecular cross-linking affect the interactions of calmodulin with Ca(2+) and enzymes.

SARS: UK public health response--past, present and future.

The emergence of severe acute respiratory syndrome (SARS) in China, the occurrence of epidemics of SARS in China and a number of Southeast Asian countries, and its spread to countries elsewhere, have presented major challenges to public health systems throughout the world. Although very few true cases of SARS were detected in the United Kingdom, the public health response to the threat of SARS was considerable. The main components of this response were the early detection, isolation and reporting of cases, and the provision of comprehensive information to health professionals, cases, their contacts and the public. The development of the response to SARS raised a number of more general issues relevant to future infectious epidemic threats. Although the World Health Organisation has now declared SARS 'contained', the possibility of re-emergence is ever present. All countries will need to be vigilant and plan their response to the possibility of a renewed SARS epidemic.

Estimation of capping incidence by indentation fracture tests.

The purpose of this study was to predict the capping tendencies of pharmaceutical powders by creating indentation fracture on compacts. Three sets of binary mixtures containing different concentrations of each ingredient were used in the study. The binary mixtures were chosen to represent plastic-plastic, plastic-brittle, and brittle-brittle combination of materials. The mixtures were tableted at different pressures and speeds on Prester, a tablet press simulator. These mixtures were also compacted on the Instron Universal Testing Machine 4502. Static indentation tests were done on these compacts at different depths until surface cracking and chipping were observed. The extent of surface cracking and chipping was observed from light microscope and scanning electron microscope images. A rank order correlation was observed between lamination susceptibility and the depth at which indentation failure occurred. It was concluded that indentation fracture tests could provide a useful estimate of lamination properties of pharmaceutical powders.

Practical limitations of tableting indices.

The purpose of this study was to utilize tableting indices to distinguish between materials with varying degrees of compactibility by establishing a quantitative relationship between indices and compactibility. Compactibility in this study is restricted to tablet strength and friability alone. Nine mixtures with varying degrees of compactibility were tableted and the tensile strength and friability of the tablets were determined. The tableting indices of these mixtures were determined using an Instron Universal testing machine. An artificial neural network program was used to establish a quantitative relationship between indices and tablet strength and friability. Six new powders were used to validate the models describing the relationship between indices and tablet strength and friability. These powders were compressed into tablets and their strength and friability were determined. Their indices were also determined. The established models were used to predict tablet strength and friability from index values. The predicted values were compared with the experimentally determined values. There was little correlation between the predicted and experimentally determined values for tablet strength and friability. It was also found that materials or mixtures having almost similar indices had remarkably different compactibilities. It was concluded that models created to predict compactibility using one set of materials may not be able to successfully predict the compactibility of a new material. This calls into question the practicality of indices.

Vertebroplasty.

Vertebroplasty is the percutaneous placement of polymethylmethacrylate (PMMA) into vertebral compression fractures for relief of pain. Polymethylmethacrylate is the cement used by orthopedic surgeons for rapid stable fixation of prosthetics in living bone. While the exact mechanism of pain relief is unknown, it is believed that the delivery of the PMMA into the fracture stabilizes the vertebral body, obtaining an analgesic effect. Vertebroplasty is an outpatient procedure that is performed with the aid of fluoroscopy. It has a high benefit/risk ratio with high success rates in comparison to extremely low complication rates. These patients consist of elderly osteoporotic patients that often times have underlying medical conditions or younger patients suffering from steroid or metastatic induced compression fractures. These patients are considered to be poor surgical candidates. In the past, this patient population has been relegated to epidural steroid injections, epidural catheters, or time contingent narcotics to control the pain. These conservative measures often lead to a patient with decreased activities of daily living and uncontrolled pain. Vertebroplasty provides a safe procedure that allows for long-term pain relief, decreased use of medication, and increased activities of daily living. This article is a review of the history, indications, contraindications, and key outcome studies. The technique is described along with complications, preprocedural care, and postprocedural care.

Discography.

Discography is a diagnostic tool that has been used for many years. Although controversial, it provides a physiologic test for evaluation of a disc with a volumetric, manometric, radiographic, and pain-provocative challenge. Although it has a controversial past, when the anatomy and pathophysiology are considered particularly in relation to intradiscal pressure and applied loads (that correlate with daily activities of the patient), the interpretation of the results of discography become more objective and reproducible. As with any procedure, indications for patient selection are an important step in successful outcomes. The equipment and technique used for performing discography using a manometry system are described in this article, as are a review of complications and outcomes. Discography is a safe, accurate, reproducible, objective diagnostic tool when tested for volume, pressure, fluoroscopic changes, and pain provocation.