Design standards for experimental and field studies to evaluate diagnostic accuracy of tests for infectious diseases in aquatic animals.

Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature.

A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

Outcomes of intravenous tissue plasminogen activator for acute ischaemic stroke in HIV-infected adults.

BACKGROUND AND PURPOSE: To our knowledge there are no studies reporting the use and short-term outcomes of intravenous tissue plasminogen activator (IV-TPA) for the treatment of acute ischaemic stroke (AIS) in people living with HIV. METHODS: The US Nationwide Inpatient Sample (NIS) (2006-2010) was searched for HIV-infected AIS patients treated with IV-TPA. RESULTS: In the NIS, 2.2% (62/2877) of HIV-infected AIS cases were thrombolyzed with IV-TPA (median age 52 years, range 27-78, 32% female, 22% Caucasian) vs. 2.1% (19 335/937 896) of HIV-uninfected cases (median age 72 years, range 17-102 years, 50% female, 74% Caucasian; P = 0.77). There were more deaths in HIV-infected versus uninfected patients with stroke (220/2877, 7.6% vs. 49 089/937 547, 5.2%, P < 0.001) but no difference in the proportion of deaths amongst IV-TPA-treated patients. The age- and sex-adjusted odds ratio for death following IV-TPA administration in HIV-infected versus uninfected patients was 2.26 (95% CI 1.12, 4.58), but the interaction on mortality between HIV and IV-TPA use was not statistically significant, indicating no difference in risk of in-hospital death by HIV serostatus with IV-TPA use. A higher number of HIV-infected patients remained in hospital versus died or were discharged at both 10 and 30 days (P < 0.01 at 10 and 30 days). No difference in the proportion of intracerebral hemorrhage in the two groups was found (P = 0.362). CONCLUSIONS: The in-hospital mortality is higher amongst HIV-infected AIS patients than HIV-uninfected patients. However, the risk of death amongst HIV-infected patients treated with IV-TPA is similar to HIV-uninfected groups.

Protein folding and misfolding in the neurodegenerative disorders: a review.

Protein misfolding is an intrinsic aspect of normal folding within the complex cellular environment. Its effects are minimized in living system by the action of a range of protective mechanisms including molecular chaperones and quality control systems. According to the current growing research, protein misfolding is a recognized key feature of most neurodegenerative diseases. Extensive biochemical, neuropathological, and genetic evidence suggest that the cerebral accumulation of amyloid fibrils is the central event in the pathogenesis of neurodegenerative disorders. In the first part of this review we have discussed the general course of action of folding and misfolding of the proteins. Later part of this review gives an outline regarding the role of protein misfolding in the molecular and cellular mechanisms in the pathogenesis of Alzheimer's and Parkinson along with their treatment possibilities. Finally, we have mentioned about the recent findings in neurodegenerative diseases.

Using a mobile phone-based application as an adjunct to facilitate oral hygiene practices in children with Attention Deficit Hyperactivity Disorder (ADHD).

AIM: To evaluate the efficacy of a mobile phone application to facilitate oral hygiene practices in children with ADHD. METHODS: This was a randomized controlled study that included 54 ADHD children after obtaining informed parental consent. The children were randomly divided into 2 groups; Group 1 (conventional) participants were instructed verbally as well as demonstrated the brushing technique on models. Group 2 (mobile phone application) participants were made to download and use the 'BRUSH DJ' app developed by Ben Underwood. At baseline, the oral hygiene index-simplified (OHI-S) [Greene and Vermillion, 1964] of each child was evaluated clinically and the parents were asked to fill a questionnaire regarding the oral hygiene practices followed by their child every day. At the end of the second, sixth, and twelfth week, the parents were asked to fill the same questionnaire in addition to the evaluation of the OHI-S index. RESULTS: A significant difference was found in the brushing time, brushing frequency, and OHI-S index between group 1 and group 2 at the end of 12 weeks. (unpaired t-test, p<0.05) CONCLUSION: The mobile phone application proved to be an effective tool in captivating the attention of these children and thus improving their oral health.

Genetic and molecular analysis of leaf blast resistance in Tetep derived line RIL4 and its relationship to genes at Pita/Pita2 locus.

The Vietnamese indica landrace 'Tetep' is known worldwide for its durable and broad spectrum-resistance to blast. We performed genetic and molecular analyses of leaf blast resistance in a Tetep derived recombinant inbred line 'RIL4' which is resistant to both leaf and neck blast. Phenotypic analysis of segregating F2 progenies suggested that leaf blast resistance in RIL4 was controlled by a dominant gene tentatively designated as Pi-l(t). The gene was mapped to a 2.4 cm region close to the centromere of chromosome 12. The search for the gene content in the equivalent genomic region of reference cv. Nipponbare revealed the presence of five NBS-LRR genes, two of which corresponded to the alleles of Pita and Pi67 genes previously identified from Tetep. The two other genes, LOC_Os12g17090, and LOC_Os12g17490 represented the homologs of stripe rust resistance gene Yr10. The allelic tests with Pita2 and Pi67 lines suggested that the leaf blast resistance gene in RIL4 is either allelic or tightly linked to these genes. The genomic position of the leaf blast resistance gene in RIL4 perfectly coincided with the genomic position of a neck blast resistance gene Pb2 previously identified from this line suggesting that the same gene confers resistance to leaf and neck blast. The present results were discussed in juxtaposition with past studies on the genes of Pita/Pita2 resistance gene complex.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

A mechanistic physiologically based model to assess the effect of study design and modified physiology on formulation safe space for virtual bioequivalence of dermatological drug products.

Physiologically based pharmacokinetic (PBPK) models are widely accepted tools utilised to describe and predict drug pharmacokinetics (PK). This includes the use of dermal PBPK models at the regulatory level including virtual bioequivalence (VBE) studies. The current work considers the Topicort® Spray formulation, which contains 0.25% desoximetasone (DSM), as an example formulation. Quantitative formulation composition and in vitro permeation testing (IVPT) data were obtained from the public literature to develop a mechanistic model using the multi-phase, multi-layer (MPML) MechDermA IVPT module in the Simcyp Simulator. In vitro-in vivo extrapolation functionality was used to simulate in vivo PK for various scenarios and predict a 'safe space' for formulation bioequivalence using the VBE module. The potential effect of vasoconstriction, impaired barrier function, and various dosing scenarios on the formulation safe space was also assessed. The model predicted 'safe space' for formulation solubility suggesting that a 50% change in solubility may cause bio-in-equivalence, whereas viscosity could deviate by orders of magnitude and the formulation may still remain bioequivalent. Evaporation rate and fraction of volatile components showed some sensitivity, suggesting that large changes in the volume or composition of the volatile fraction could cause bio-in-equivalence. The tested dosing scenarios showed decreased sensitivity for all formulation parameters with a decreased dose. The relative formulation bioequivalence was insensitive to vasoconstriction, but the safe space became wider with decreased barrier function for all parameters, except viscosity that was unaffected.

Spectrum of coronary angiographic findings in patients with ST Elevation Myocardial Infarction (STEMI) undergoing primary PCI in a tertiary care center of Nepal.

BACKGROUND: Even in developing countries like Nepal, prevalence of ST-elevation myocardial infarction has been shown to be increased with rise in prevalence of conventional risk factors like diabetes, Hypertension, smoking, dyslipidemia and obesity. Our aim is to retrospectively analyze for various risk factors and angiographic patterns of coronary artery disease in patients with ST-elevation myocardial infarction undergoing Primary Percutaneous Intervention. RESULTS: During the period of 1 year (January 2019 to December 2019), 816 patients presented to our ER with acute STEMI, among them 437 (53.6%) patients underwent primary PCI strategy and among them 22 (5.3%) patients were died. Thirty-six (4.4%) patients received thrombolysis, among them 5 (13.9%) patients were died while remaining 343 (42.0%) patients were managed conservatively and among them 20 (5.8%) were died. The mean age of patient who underwent primary PCI was 58.5±12.7 years range from 25 years to 99 years. Among them 55-75 years old 217 (49.6%) were highest in number followed by<55 years old 180 (41.2%). Males 318 (72.8%) were predominant. Among those who underwent primary PCI, hypertension 214 (49%) was the most common risk factor, followed by smoking 198 (45.3%), diabetes mellitus 123 (28.1%), dyslipidemia 53 (12.1%) and family history of premature coronary artery disease 18 (4.1%). Among those patients, 292 patients (66.8%) had single vessel disease, 99 patients (22.7%) had double vessel disease, 41 patients (9.3%) had triple vessel disease and 5 patients (1.1%) had non-significant coronary artery stenosis. Left anterior descending (53.3%) was the most frequently found culprit artery, followed by right coronary artery, left circumflex, ramus intermedius and left main artery. CONCLUSION: Fifty percent of patients presented with acute ST-elevation myocardial infarction and underwent primary PCI were between 55-75 years of age. Hypertension and smoking were the most common risk factors present in those patients. Single vessel disease was most prevalent with left anterior descending found to be the most commonly involved coronary artery followed by right coronary artery and left circumflex.

Performance of Xpert® MTB/RIF and Xpert® Ultra for the diagnosis of tuberculous meningitis in children.

OBJECTIVE: To assess Xpert® MTB/RIF (Xpert) and Xpert® MTB/RIF Ultra (Ultra) performance in diagnosing pediatric tuberculous meningitis (TBM).METHODS: We conducted a study among children with suspected meningoencephalitis in Pune, India. Clinical, radiological, laboratory, and treatment data were analyzed to classify disease as definite, probable, possible or no TBM, using microbiologic or composite reference standards. We tested cerebrospinal fluid (CSF) either using Xpert or Ultra and estimated test performance characteristics.RESULTS: Of 341 participants, 149 (43.7%) were tested using Ultra and 192 (56.3%) with Xpert. Ultra had higher sensitivity (50% vs. 18%), lower specificity (91% vs. 99%), poor positive predictive value (PPV) (13% vs. 75%), and higher negative predictive value (NPV) (99% vs. 93%) than Xpert using the composite reference standard, with similar results by the microbiologic reference standard. Of 10 participants with trace positivity on Ultra, none met clinical TBM definitions.CONCLUSION: This is the first study to report on diagnostic performance of Ultra in pediatric TBM, which showed higher sensitivity and NPV than Xpert. For children presenting with nonspecific clinical features, Ultra is a promising diagnostic test. Further studies are required to define its optimal clinical use, including interpretation of trace positive results.

Spatial and temporal patterns in the sex ratio of American lobsters (Homarus americanus) in southwestern Nova Scotia, Canada.

An approximate 1:1 sex ratio of American lobsters can be skewed due to environmental factors or fisheries management. Substantial skewness can impact mating behaviour and lower reproduction which could have far-reaching ecological and economic consequences. The aim was to investigate the sex ratio patterns of lobsters in two lobster fishing areas (LFAs) in southwestern Nova Scotia, Canada and identify factors associated with skewed sex ratios. This study analyzed biological data from more than 270,000 lobsters sampled over ten years (2010-2019) by the Fishermen and Scientists Research Society. A mixed effect logistic regression model evaluated the effect of spatial, temporal and environmental factors as well as size on the sex ratio of lobsters. There were significant temporal patterns in sex ratios that differed by LFA. After the effects of sampling month, year and LFA were accounted for, lower bottom temperature and deeper water depth were associated with a higher prevalence of females, especially in larger lobsters. We present the first long term analyses of sex ratio patterns in H. americanus in Atlantic Canada's most commercially important region for this species and provide evidence that these patterns are influenced by environmental factors and fisheries. In view of future climate change scenarios, monitoring the population dynamics of this iconic fishery species is crucial to ensure sustainable fisheries and healthy lobster stocks.

AFLP-based molecular characterization of an elite germplasm collection of Jatropha curcas L., a biofuel plant.

Amplified fragment length polymorphism (AFLP) was employed to assess the diversity in the elite germplasm collection of Jatropha curcas, which has gained tremendous significance as a biofuel plant in India and many other countries recently. Forty-eight accessions, collected from six different states of India, were used with seven AFLP primer combinations that generated a total of 770 fragments with an average of 110 fragments per primer combination. A total of 680 (88%) fragments showed polymorphism in the germplasm analyzed, of which 59 (8.7%) fragments were unique (accession specific) and 108 (15.9%) fragments were rare (present in less than 10% accessions). In order to assess the discriminatory power of seven primer combinations used, a variety of marker attributes like polymorphism information content (PIC), marker index (MI) and resolving power (RP) values were calculated. Although the PIC values ranged from 0.20 (E-ACA/M-CAA) to 0.34 (E-ACT/M-CTT) with an average of 0.26 per primer combination and the MI values were observed in the range of 17.60 (E-ACA/M-CAA) to 32.30 (E-ACT/M-CTT) with an average of 25.13 per primer combination, the RP was recognized the real attribute for AFLP to determine the discriminatory power of the primer combination. The RP values for different primer combinations varied from 23.11 (E-ACA/M-CAA) to 46.82 (E-ACT/M-CTT) with an average of 35.21. Genotyping data obtained for all 680 polymorphic fragments were used to group the accessions analyzed using the UPGMA-phenogram and principal component analysis (PCA). Majority of groups obtained in phenogram and PCA contained accessions as per geographical locations. In general, accessions coming from Andhra Pradesh were found diverse as these were scattered in different groups, whereas accessions coming from Chhattisgarh showed occurrence of higher number of unique/rare fragments. Molecular diversity estimated in the present study combined with the datasets on other morphological/agronomic traits will be very useful for selecting the appropriate accessions for plant improvement through conventional as well as molecular breeding approaches.

Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field.

SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally.CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population.

Bacteriological profile and antibiotic sensitivity pattern of neonatal septicaemia in a rural tertiary care hospital in North India.

BACKGROUND: There is not much published literature on neonatal septicemia available for the Sub-Himalayan region of North India. Hence, we undertook this study to find out the bacteriological profile and antibiotic sensitivity pattern of neonatal septicemia in the neonatal Intensive Care Unit. MATERIAL AND METHODS: Blood cultures were performed for all clinically suspected neonatal septicemia cases for 1-year. Identification of all pathogenic isolates was followed by antibiotic sensitivity testing. RESULTS: We did blood cultures for 450 neonates and 42% were culture positive. Early onset sepsis were 92 (49%) and 96 (51%) were late onset sepsis. Gram-positive isolates were 60% and 40% were Gram-negative. Staphylococcus aureus (40%), coagulase negative Staphylococcus species (16%), non-fermenter group of organisms (NFGOs) (15%), and Klebsiella pneumoniae (10%) were the main isolates. Nasal cannula 101 (54%), birth asphyxia 91 (48%), and prematurity 73 (38%) were the prominent risk factors associated with septicemia. Gram-positive organisms were highly resistant to penicillin (87%) whereas Gram-negative isolates showed high resistance to third generation cephalosporins (53-89%) and aminoglycosides (50-67%). The S. aureus isolates were methicillin-resistant in 41% whereas extended spectrum beta lactamase production was seen in 48% Gram-negative isolates. CONCLUSION: Our study highlights the recent emergence of Gram-positive organisms as predominant cause of neonatal septicemia in this part of Sub-Himalayan region, along with the review of literature which shows similar results from North India and rest of the world too. Though Gram-negative bacteria still remain the main cause of mortality in neonatal septicemia, we want to dispel the common notion among practitioners that they are the predominant isolates in neonatal septicemia.

Analysis of Swine Movement in Four Canadian Regions: Network Structure and Implications for Disease Spread.

Direct and indirect contacts among animal holdings are important in the spread of infectious diseases. The objectives of this study were to describe networks of pig movements and the sharing of trucks used for those movements between swine farms in four Canadian regions using network analysis tools and to obtain contact parameters for infectious disease spread simulation models. Four months of swine movement data from a pilot pig traceability programme were used. Two types of networks were created using three time scales (weekly, monthly and the full study period): one-mode networks of farm-to-farm direct contact representing animal shipments and two-mode networks representing the sharing of trucks between farms. Contact patterns among farms were described by estimating a range of relevant network measures. The overall network neglecting the four regions consisted of 145 farms, which were connected by 261 distinct links. A total of 184 trucks were used to transport 2043 shipments of pigs during the study period. The median in- and out-degree for the overall one-mode network was 1 and ranged from 0 to 26 and 0 to 10, respectively. The overall one-mode network had heterogeneous degree distribution, a high clustering coefficient and shorter average path length than would be expected for randomly generated networks of similar size. On average one truck was shared by four farms in the overall network, or by three farms when considered the monthly and weekly networks. Degree distribution of the two-mode overall network demonstrated characteristics of power-law distribution. For more than 50% of shipments on any given day, the same truck was used for at least one other shipment. Findings from this study are in agreement with previous work, which suggested that swine movement networks exhibit small-world and scale-free topologies. Furthermore, trucks used for the shipment of pigs can play an important role in connecting otherwise unconnected farms and may increase the spread of disease.

Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children.

Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results.

Esophageal bezoar: a rare but distinct clinical entity.

A 89 year old female patient presented with severe dysphagia and was suspected to have carcinoma of the esophagus. Endoscopy revealed an esophageal phytobezoar which passed down spontaneously after unsuccessful endoscopic extraction attempt. Barium swallow study revealed diffuse spasm of the esophagus. A review of English literature revealed only 17 previous cases of esophageal bezoar. Salient features of esophageal bezoars are discussed based on previous reports and the current case.

Experience with intraluminal radiotherapy in advanced oesophageal cancer.

Despite improvement in the diagnostic modalities, surgical technique, chemotherapy and radiotherapy, mortality and morbidity due to carcinoma esophagus continues to be dismal. Combination of external and intraluminal radio therapy (ILRT) has emerged as a powerful and promising palliative therapy in this disease. Thirty four patients with inoperable cancer esophagus treated with ILRT during June 1991 to December 1993 were evaluated to assess its palliative effects. Seventeen of these patients had received additional chemotherapy and external radiotherapy. Thirteen patients received only radiotherapy (both external radiotherapy + ILRT) and the remaining 4 received only ILRT. They were followed up for a mean period of 8.3 months (range 2 to 28 months) during which one patient was lost to follow up. Eight had a follow up of less than 6 months. Eight (33%) amongst the remaining 25 patients were considered disease free, 15 had recurrent and progressive disease, one developed metastasis and one patient died. In 21 (66%) dysphagia markedly improved. Nine (26%) patients survived beyond 1 year and the median survival for all patients was 8 months. Associated radiation morbidity was documented in 13 (38%) patients. We conclude that combination of external radiotherapy and ILRT is an effective and safe therapy for inoperable esophageal malignancies.

Shima drinking water--a bacteriological analysis.

300 water samples, 60 from piped supply and 240 from 20 natural sources were analyzed bacteriologically for four important bacterial indicators every month over a period of one year. The MPN of total coliforms, Escherichia coli, Streptococcus faecalis were detected by multiple tube method and Clostridium perfringens was isolated using litmus milk medium. From piped water supply, only one sample was found unfit for human consumption. The plate count at 37 degrees C and 22 degrees C varied from 0.5 x 10(3) to 15 x 10(3) per ml. of water. From natural sources, MPN indices for coliforms, Esch. coli and S. faecalis varied from 3 to > 1800, 0 to > 1800 and 0 to 540 per 100 ml. of water respectively. About 1/3rd of samples showed presence of Cl. perfringens. The plate count varied from 1.0 x 10(3) to > 150 x 10(3) per ml. of water. Salmonella typhi was isolated in 1.25% samples by membrane filtration technique. The water from all the natural sources was unfit for human consumption whereas piped water supply was of good quality in general.