The burden of COVID-19 infection in a rural Tamil Nadu community.

BACKGROUND: There have been over 30 million cases of COVID-19 in India and over 430,000 deaths. Transmission rates vary from region to region, and are influenced by many factors including population susceptibility, travel and uptake of preventive measures. To date there have been relatively few studies examining the impact of the pandemic in lower income, rural regions of India. We report on a study examining COVID-19 burden in a rural community in Tamil Nadu. METHODS: The study was undertaken in a population of approximately 130,000 people, served by the Rural Unit of Health and Social Affairs (RUHSA), a community health center of CMC, Vellore. We established and evaluated a COVID-19 PCR-testing programme for symptomatic patients-testing was offered to 350 individuals, and household members of test-positive cases were offered antibody testing. We also undertook two COVID-19 seroprevalence surveys in the same community, amongst 701 randomly-selected individuals. RESULTS: There were 182 positive tests in the symptomatic population (52.0%). Factors associated with test-positivity were older age, male gender, higher socioeconomic status (SES, as determined by occupation, education and housing), a history of diabetes, contact with a confirmed/suspected case and attending a gathering (such as a religious ceremony, festival or extended family gathering). Amongst test-positive cases, 3 (1.6%) died and 16 (8.8%) suffered a severe illness. Amongst 129 household contacts 40 (31.0%) tested positive. The two seroprevalence surveys showed positivity rates of 2.2% (July/Aug 2020) and 22.0% (Nov 2020). 40 tested positive (31.0%, 95% CI: 23.02 - 38.98). Our estimated infection-to-case ratio was 31.7. CONCLUSIONS: A simple approach using community health workers and a community-based testing clinic can readily identify significant numbers of COVID-19 infections in Indian rural population. There appear, however, to be low rates of death and severe illness, although vulnerable groups may be under-represented in our sample. It's vital these lower income, rural populations aren't overlooked in ongoing pandemic monitoring and vaccine roll-out in India.

Memristive effects in oxygenated amorphous carbon nanodevices.

Computing with resistive-switching (memristive) memory devices has shown much recent progress and offers an attractive route to circumvent the von-Neumann bottleneck, i.e. the separation of processing and memory, which limits the performance of conventional computer architectures. Due to their good scalability and nanosecond switching speeds, carbon-based resistive-switching memory devices could play an important role in this respect. However, devices based on elemental carbon, such as tetrahedral amorphous carbon or ta-C, typically suffer from a low cycling endurance. A material that has proven to be capable of combining the advantages of elemental carbon-based memories with simple fabrication methods and good endurance performance for binary memory applications is oxygenated amorphous carbon, or a-CO x . Here, we examine the memristive capabilities of nanoscale a-CO x devices, in particular their ability to provide the multilevel and accumulation properties that underpin computing type applications. We show the successful operation of nanoscale a-CO x memory cells for both the storage of multilevel states (here 3-level) and for the provision of an arithmetic accumulator. We implement a base-16, or hexadecimal, accumulator and show how such a device can carry out hexadecimal arithmetic and simultaneously store the computed result in the self-same a-CO x cell, all using fast (sub-10 ns) and low-energy (sub-pJ) input pulses.

Rift Valley fever virus infections in Egyptian cattle and their prevention.

Rift Valley fever virus (RVFV) causes consistently severe outbreaks with high public health impacts and economic losses in livestock in many African countries and has also been introduced to Saudi Arabia and Yemen. Egypt with its four large outbreaks in the last 40 years represents the northernmost endemic area of RVFV. The purpose of this study was to provide an insight into the current anti-RVFV antibody status in immunized as well as non-immunized dairy cattle from the Nile Delta of Egypt. During 2013-2015, a total of 4,167 dairy cattle from four governorates including Dakahlia, Damietta, Gharbia and Port Said were investigated. All cattle were born after 2007 and therewith after the last reported Egyptian RVFV outbreak in 2003. The samples derived from vaccinated animals from 26 different dairy farms as well as non-immunized cattle from 27 different smallholding flocks. All samples were examined following a three-part analysis including a commercially available competition ELISA, an in-house immunofluorescence assay and a virus neutralization test. Additionally, a subset of samples was analysed for acute infections using IgM ELISA and real-time reverse transcriptase PCR. The results indicated that the RVFV is still circulating in Egypt as about 10% of the non-immunized animals exhibited RVFV-specific antibodies. Surprisingly, the antibody prevalence in immunized animals was not significantly higher than that in non-vaccinated animals which points out the need for further evaluation of the vaccination programme. Due to the substantial role of livestock in the amplification and transmission of RVFV, further recurrent monitoring of the antibody prevalence in susceptible species is highly warranted.

Serological and genomic evidence of Rift Valley fever virus during inter-epidemic periods in Mauritania.

Rift Valley fever virus (RVFV) is an emerging pathogen of major concern throughout Africa and the Arabian Peninsula, affecting both livestock and humans. In the past recurrent epidemics were reported in Mauritania and studies focused on the analysis of samples from affected populations during acute outbreaks. To verify characteristics and presence of RVFV during non-epidemic periods we implemented a multi-stage serological and molecular analysis. Serum samples of small ruminants, cattle and camels were obtained from Mauritania during an inter-epidemic period in 2012-2013. This paper presents a comparative analysis of potential variations and shifts of antibody presence and the capability of inter-epidemic infections in Mauritanian livestock. We observed distinct serological differences between tested species (seroprevalence: small ruminants 3·8%, cattle 15·4%, camels 32·0%). In one single bovine from Nouakchott, a recent RVF infection could be identified by the simultaneous detection of IgM antibodies and viral RNA. This study indicates the occurrence of a low-level enzootic RVFV circulation in livestock in Mauritania. Moreover, results indicate that small ruminants can preferably act as sentinels for RVF surveillance.

Microfluidic blood plasma separation for medical diagnostics: is it worth it?

Circulating biomarkers are on the verge of becoming powerful diagnostic tools for various human diseases. However, the complex sample composition makes it difficult to detect biomarkers directly from blood at the bench or at the point-of-care. Blood cells are often a source of variability of the biomarker signal. While the interference of hemoglobin is a long known source of variability, the release of nucleic acids and other cellular components from hemocytes is a new concern for measurement and detection of circulating extracellular markers. Research into miniaturised blood plasma separation has been thriving in the last 10 years (2006-2016). Most point-of-care systems need microscale blood plasma separation, but developed solutions differ in complexity and sample volume range. But could blood plasma separation be avoided completely? This focused review weights the advantages and limits of miniaturised blood plasma separation and highlights the most interesting advances in direct capture as well as smart blood plasma separation.

Highly Pathogenic Avian Influenza H5N8 in Germany: Outbreak Investigations.

Epidemiological outbreak investigations were conducted in highly pathogenic avian influenza virus of the subtype H5N8 (HPAIV H5N8)-affected poultry holdings and a zoo to identify potential routes of entry of the pathogen via water, feedstuffs, animals, people, bedding material, other fomites (equipment, vehicles etc.) and the presence of wild birds near affected holdings. Indirect introduction of HPAIV H5N8 via material contaminated by infected wild bird seems the most reasonable explanation for the observed outbreak series in three commercial holdings in Mecklenburg-Western Pomerania and Lower Saxony, while direct contact to infected wild birds may have led to outbreaks in a zoo in Rostock and in two small free-range holdings in Anklam, Mecklenburg-Western Pomerania.

Does the P300 reflect conscious perception or its consequences?

A common scientific strategy toward understanding consciousness is to study neural correlates of consciousness (NCC) for a particular conscious percept. This can be done by contrasting conditions in which subjects are aware and unaware of a particular visual stimulus. However, recent findings have been contradictory and this approach appears not to reveal only the NCC, but also the prerequisites or consequences of consciousness. The goal of the present study was to investigate whether the P300 component often claimed to be a key signature of conscious access might actually rather reflect the consequences of conscious perception. Subjects participated in an electroencephalography (EEG) experiment where most of the stimuli were clearly perceived and only a quarter of trials was associated with not perceiving the target. The visual masking paradigm used no discrimination task, always the same stimulus was presented and an additional task was given together with the target stimulus. Results indicate that trials where subjects reported to have seen the stimulus are associated with a more pronounced P300. Hence, the present data support the theories which claim that P300 is a marker of conscious perception. However, an earlier component, visual awareness negativity also tracks conscious perception reliably so that the P300 need not be the earliest correlate of conscious perception.

Development of a PCR-free electrochemical point of care test for clinical detection of methicillin resistant Staphylococcus aureus (MRSA).

An MRSA assay requiring neither labeling nor amplification of target DNA has been developed. Sequence specific binding of fragments of bacterial genomic DNA is detected at femtomolar concentrations using electrochemical impedance spectroscopy (EIS). This has been achieved using systematic optimisation of probe chemistry (PNA self-assembled monolayer film on gold electrode), electrode film structure (the size and nature of the chemical spacer) and DNA fragmentation, as these are found to play an important role in assay performance. These sensitivity improvements allow the elimination of the PCR step and DNA labeling and facilitate the development of a simple and rapid point of care test for MRSA. Assay performance is then evaluated and specific direct detection of the MRSA diagnostic mecA gene from genomic DNA, extracted directly from bacteria without further treatment is demonstrated for bacteria spiked into saline (10(6) cells per mL) on gold macrodisc electrodes and into human wound fluid (10(4) cells per mL) on screen printed gold electrodes. The latter detection level is particularly relevant to clinical requirements and point of care testing where the general threshold for considering a wound to be infected is 10(5) cells per mL. By eliminating the PCR step typically employed in nucleic acid assays, using screen printed electrodes and achieving sequence specific discrimination under ambient conditions, the test is extremely simple to design and engineer. In combination with a time to result of a few minutes this means the assay is well placed for use in point of care testing.

Haematological side effects of antiepileptic drug treatment in patients with epilepsy.

OBJECTIVES: Little is known about the haematological side effects of the newer antiepileptic drugs (AEDs), but recent case reports have raised concerns regarding the possibility of altered thrombocyte counts or function in some patients during levetiracetam (LEV) treatment. The aim of our study was to investigate haematological changes in patients treated with the newer AEDs, LEV and lamotrigine (LTG), compared with the older AEDs, valproate (VPA) and carbamazepine (CBZ). METHODS: This cross-sectional study included 251 patients with epilepsy of both genders, aged 18-45 years, using AED monotherapy: 52 patients on LEV (31 men, 21 women), 80 on LTG (37 men, 43 women), 90 on CBZ (61 men, 29 women), 29 on VPA (15 men, 14 women), and 79 healthy controls (36 men, 43 women). Haemoglobin (Hb), white blood cells (WBC) and platelet (thrombocyte) counts were estimated. The subjects were recruited from hospitals in south-eastern Norway and Innsbruck, Austria. RESULTS: Significantly lower platelet counts were recorded in both men and women on LEV monotherapy. In the LEV group, platelets were 14% lower (40.68 × 10(9) /l lower) than in the control group. There was no difference according to sex or age of the patients. Only minor changes in haematological parameters were observed for the other drugs investigated. CONCLUSIONS: Both men and women treated with LEV monotherapy have lower blood platelet counts than healthy controls, with no difference in Hb or WBC. Haematological changes observed with the other AEDs were minor.

Multiparametric determination of genes and their point mutations for identification of beta-lactamases.

More than half of all currently used antibiotics belong to the beta-lactam group, but their clinical effectiveness is severely limited by antibiotic resistance of microorganisms that are the causative agents of infectious diseases. Several mechanisms for the resistance of Enterobacteriaceae have been established, but the main one is the enzymatic hydrolysis of the antibiotic by specific enzymes called beta-lactamases. Beta-lactamases represent a large group of genetically and functionally different enzymes of which extended-spectrum beta-lactamases (ESBLs) pose the greatest threat. Due to the plasmid localization of the encoded genes, the distribution of these enzymes among the pathogens increases every year. Among ESBLs the most widespread and clinically relevant are class A ESBLs of TEM, SHV, and CTX-M types. TEM and SHV type ESBLs are derived from penicillinases TEM-1, TEM-2, and SHV-1 and are characterized by several single amino acid substitutions. The extended spectrum of substrate specificity for CTX-M beta-lactamases is also associated with the emergence of single mutations in the coding genes. The present review describes various molecular-biological methods used to identify determinants of antibiotic resistance. Particular attention is given to the method of hybridization analysis on microarrays, which allows simultaneous multiparametric determination of many genes and point mutations in them. A separate chapter deals with the use of hybridization analysis on microarrays for genotyping of the major clinically significant ESBLs. Specificity of mutation detection by means of hybridization analysis with different detection techniques is compared.

Different effects of the two types of spatial pre-cueing: what precisely is "attention" in Di Lollo's and Enns' substitution masking theory?

Enns and Di Lollo [Psychological Science, 8 (2), 135-139, 1997] have introduced the object substitution theory of visual masking. Object substitution masking occurs when focusing attention on the target is delayed. However, Posner (Quarterly Journal of Experimental Psychology, 32, 3-25, 1980) has already shown that attention can be directed to a target at least in two ways: intentionally (endogenously) and automatically (exogenously). We conducted two experiments to explore the effects of endogenous and exogenous cues on substitution masking. The results showed that when attention was shifted to the target location automatically (using a local peripheral pre-cue), masking was attenuated. A decrease in target identification dependent on a delay of mask offset, typical to substitution masking, was not observed. However, strong substitution masking occurred when the target location was not pre-cued or when attention was directed to the target location intentionally (using a symbolic pre-cue displayed centrally). The hypothesis of two different mechanisms of attentional control in substitution masking was confirmed.

Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection-long term results.

BACKGROUND: It is not known whether pylorus-preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures. METHODS: Clinical data, histological findings, short-term results, survival and quality of life of all patients having surgery for suspected pancreatic or periampullary cancer between June 1996 and September 2001 were analysed. RESULTS: Two hundred and fourteen patients were randomized to undergo either a standard or a pylorus-preserving Whipple resection. After exclusion of 84 patients on the basis of intraoperative findings, 130 patients (66 standard Whipple operation and 64 pylorus-preserving resection) were entered into the trial. Of these, 110 patients with proven adenocarcinoma (57 standard Whipple and 53 pylorus-preserving resection) were analysed for long-term survival and quality of life. There was no difference in perioperative morbidity. Long-term survival, quality of life and weight gain were identical after a median follow-up of 63.1 (range 4-93) months. At 6 months, capacity to work was better after the pylorus-preserving procedure (77 versus 56 per cent; P = 0.019). CONCLUSION: Both procedures were equally effective for the treatment of pancreatic and periampullary cancer. Pylorus-preserving Whipple resection offers some minor advantages in the early postoperative period, but not in the long term.

A long insertion reverts the functional effect of a substitution in acetylcholinesterase.

Proteins are thought to undertake single substitutions, deletions and insertions to explore the fitness landscape. Nevertheless, the ways in which these different kind of mutations act together to alter a protein phenotype remain poorly described. We introduced incrementally the single substitution W290A and a 26 amino acid long insertion at the 297 location in the Nippostrongylus brasiliensis acetylcholinesterase B sequence and analysed in vitro the induced changes in the hydrolysis rate of three hemi-substrates: pirimicarb, paraoxon methyl and omethoate. The substitution decreased the hydrolysis rate of the three hemi-substrates. The insertion did not influence this kinetic alteration induced by the substitution for the former hemi-substrate, but reverted it for the two others. These results show that two different kinds of mutations can interact together to influence the direction of a protein's adaptative walk on the fitness landscape.

Bioavailable nitrate detection in water by an immobilized luminescent cyanobacterial reporter strain.

Cyanobacteria are a major group of photosynthetic bacteria that can accumulate in surface water as so-called "blooms" in response to environmental factors such as temperature, light and certain nutrients such as N, P, and Fe. Some species of cyanobacteria produce toxins, causing a considerable danger for human and livestock health. As a consequence, monitoring of bloom formation and toxin production of drinking water supplies has become a major concern. To enable prediction and monitoring of cyanobacterial blooms, tools to detect nutrient bioavailability in water would be advantageous. A whole-cell biosensor was developed for monitoring nitrate (NO(3-)) bioavailability in aquatic ecosystems using the recombinant bioluminescent cyanobacterial strain Synechocystis PCC 6803 harboring an insertion of a luxAB-kmr fusion with nblA1 in its chromosomal DNA, leading to PnblA::luxAB-kmr. This reporter strain was designated N1LuxKm. Cells were immobilized in microtiter plates and showed a dose-dependent response to nitrate deprivation. The resultant CyanoSensor could detect nitrate in the 4-100 micro M concentration range after a sample incubation time of 10 h under continuous illumination (50 micro E m(-2) s(-1)). The optimal temperature for sensor operation was 29 degrees C and the immobilized biosensor could be stored at 4 degrees C in dark for about 1 month without significant loss of sensitivity.

Study of the structure of passivated vanadium-titanium alloys and their semiconductor properties.

The possibility of investigating the photocurrent behavior and structure of electrochemically prepared passive films on metallic titanium and on binary vanadium-titanium alloys has been demonstrated. The semiconductor properties were characterized by measuring the dependence of the photocurrent on the wavelength of the incident light and on the electrode potential. The results showed the oxide layers to be n-type semiconductors with a bandgap between 2.6 and 3.3 eV and a flatband potential of approximately -300 to +400 mV (relative to the SCE). The results were interpreted in terms of the corrosion characteristics of the materials. XPS measurements on pure vanadium and some alloys are presented. Several properties were used to characterize the passive surface of these materials. The V(2)O(5) and TiO(2) content decreases with increasing depth.

A disposable acetylcholinesterase-based electrode biosensor to detect anatoxin-a(s) in water.

Anatoxin-a(s) is a hazardous toxin released by cyanobacteria during bacterial blooms. A simple and fast method to detect this hazardous compound using a biosensor based on the electrochemical detection of the activity of acetylcholinesterase was developed. Among several acetylcholinesterases, electric eel enzyme was found to be the most sensitive to anatoxin-a(s) and was thus used to build disposable amperometric sensors. The system displayed a detection limit of 1 microg/L anatoxin-a(s). No unspecific effect was noticed with real water samples but spiked toxin was accurately detected. Oxime reactivation was used to discriminate between the toxin and potential insecticides present in the sample.

Monitoring of phosphorus bioavailability in water by an immobilized luminescent cyanobacterial reporter strain.

Massive growth of cyanobacteria, known as "algal blooms", has become a major concern for water monitoring. It has been observed that environmental factors like temperature, light, and certain patterns of availability of nutrients such as P, N, Fe influence cyanobacterial proliferation and toxin production. In order to monitor nutrients in aquatic ecosystems, an assay for monitoring phosphorus bioavailability to cyanobacteria was developed. The test consists of an immobilized luminescent reporter strain of Synechococcus PCC 7942, designated APL. The reporter strain harbours the gene coding the reporter protein luciferase from Vibrio harveyi under control of the inducible alkaline phosphatase promoter from Synechococcus PCC 7942, and can be induced under phosphorus limitation. The resultant CyanoSensor detects PO(3-)(4)-P in a concentration range of 0.3-8 microM after a sample incubation time of 8 h under continuous illumination (50 microE m(-2) s(-1)). The sensor also responded to a variety of organic phosphorus sources and was storable for 3 weeks at 4 degrees C. It could be demonstrated that the CyanoSensor for bioavailability monitoring is an improvement to conventional phosphorus detection methods.

Expression level of heterologous proteins in Pichia pastoris is influenced by flask design.

The yeast Pichia pastoris is a convenient production system that enables expression of heterologous proteins in high amounts. As a fermentation method, shaking flasks are very popular because of their simplicity of handling and their low cost. We compared the expression level of the enzyme acetylcholinesterase in a transformed strain of P. pastoris grown in different flasks, presenting various designs but all with the same volume. A several-thousand-fold difference appeared in the expression levels; and the results could not be explained by differences between the flasks in the oxygenation of the medium. The data show that flask design is an important factor to consider for optimising fermentation processes.

Change in feature space is not necessary for the flash-lag effect.

To achieve perceptual match between a flashed target and a gradually changing one, the flashed target should have the feature value corresponding to the value to be obtained by the gradually changing target only later. Flashed target should be positioned ahead of the continuously moving one in order to be perceived as aligned (Nijhawan (1994). Nature, 370, 256-257); with continuously changing colour, spatial frequency, pattern entropy or luminance, the flashed target should have feature value which changing target obtains only later (Sheth, Nijhawan, & Shimojo (2000). Nature Neuroscience, 3, 489-495). It was found that flash-lag effect is present even if the continuously accumulating pre- and post-target input consists in spatially and featurally invariant stimulation. The perceptual precedence of the target in stream over its synchronous single-flashed replica may result from perceptual acceleration where newly arriving visual signals are facilitated by the locally preceding stimulation.