A framework for assessing the potential for a double dividend from a policy-induced reduction in alcohol consumption on the economy.

OBJECTIVES: Tax policies targeted at reducing alcohol consumption are typically understood to be associated with economic losses, including in alcohol production and trade sectors. This study sought to determine whether the overall effect of reduced alcohol consumption might be positive once improvements in productivity associated with reduced alcohol-related consumption are considered. STUDY DESIGN: This study used Computable General Equilibrium economic modelling. METHODS: An economic modelling framework was developed for Scotland, which considered the fiscal and economic impacts of alcohol taxation and the economy-wide impacts. Simulation of hypothetical alcohol taxes and improvements in labour productivity calibrated on losses due to absenteeism and presenteeism in Scotland in 2017. RESULTS: The long-run impacts of a five pence increase in taxation alone produce negative economic impacts on jobs and Gross Domestic Product in Scotland (1189 jobs and £71.12 million). These effects are reduced by half - but remain negative - when the revenues from such policy are recycled to the economy through government spending. A small improvement in labour productivity - equivalent to 4.95% of the total productivity gap from absenteeism and presenteeism estimated for Scotland - would be sufficient to turn the economic consequence non-negative. CONCLUSIONS: The overall macroeconomic impact of policies targeted at alcohol consumption should include consideration of the potential productivity effect and that impact studies that do not include such mechanisms are likely to overstate the negative economic impacts of alcohol policies.

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome.

BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS: The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.

Ovarian steroid cell tumor, not otherwise specified.

Ovarian steroid cell tumours are rare virilizing tumours. They are three types of tumours of ovary which are characterized by steroid cell proliferation : Leydig cell tumour, steroid cell tumour, Not Otherwise Specified (NOS) and stromal luteoma. Here we present a case of 36 year old female, who presented with history of weight loss since last two and half months. There is history of amenorrhoea and hirsuitism. Her CA was 125: 11.4 IU/ml (0-35 U/mL). Blood Testosterone levels was elevated with value of 150 ng/ml (5.71-77 ng/ml). Serum Inhibin A, Inhibin B, FSH, LH and prolactin were within normal limits. The steroid cell tumour, NOS are mostly benign but few of them behave in malignant fashion. Hayes and Scully gave few histopathological features which favour malignant behavior. These tumours should be differentiated from leydig cell tumour by lack of cytoplasmic Reinkes' crystals as well as from other neoplasms like primary clear cell carcinoma, metastatic clear cell renal cell carcinoma and adrenocortical tumour.

Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.

BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma-actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next-generation sequencing. KEY RESULTS: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis-microcolon-intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. CONCLUSIONS AND INFERENCES: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.

Adenoid cystic carcinoma: a rare breast carcinoma.

Adenoid cystic carcinoma is a rare neoplasm accounting for <0.1% of breast carcinomas. The mean age of presentation is fifth to sixth decade of life and it generally presents as a painful breast lump. The histological features are characteristic with cribriform and acinar pattern of basaloid cells. It is triple negative tumor with CD117 and p63 positivity and excellent prognosis.

Leishman and Giemsa stain: a new reliable staining technique for blood/bone marrow smears.

INTRODUCTION: Peripheral blood and bone marrow smear examination is an important basic tool for the diagnosis of different haematological conditions including haematological malignancies. We created a newer modification of the conventional Leishman and Giemsa stains as Leishman and Giemsa (L&G) stain and compared the efficacy and reliability of this stain with conventional stains. The study was performed to evaluate the staining efficacy, feasibility, time and cost of L&G stain over the conventional Leishman and Giemsa stains. METHODS: A pilot study was carried out in the Department of Haematology of our hospital from October 2013 to December 2013. Hundred selected cases, each with peripheral blood and bone marrow smears were taken, and three sets of the smears were prepared from each sample--one for L&G stain and other two--one each for conventional Leishman and Giemsa stains. This staining is further incorporated in our routine standard operating protocols for staining of all the peripheral blood smears in automated stainer, Sysmex SP10. RESULT: The average grading score from each staining methods from all the three experts was compiled. The average grading score of L&G staining method was noted to be significantly higher than the other two methods (analysis of variance test, P value < 0.05). When modified L&G stain (C) was compared with stain conventional stains (A and B), a P value of <0.001 was noted in all parameters except between Leishman stain and L&G stain in mature RBC and WBC nucleus and RBC inclusions (P value between 0.05 and 0.001). CONCLUSION: L&G staining is a newer staining technique of immense help in high-throughput haematology laboratories by offering a time-saving, cost-effective and better staining option to conventional staining methods. It gives a better nuclear and cytoplasmic differential staining and can also be used in automated blood counters/stainer.

Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites.

OBJECTIVE: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. METHODS: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. RESULT: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. CONCLUSION: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.

Bilateral endogenous panophthalmitis caused by Salmonella typhi: first case report.

Metastatic bilateral endogenous panophthalmitis is a rare but devastating ocular infection. A young male presented with high-grade fever of 4 days duration along with rapidly progressive proptosis and loss of vision in both eyes. Systemic examination revealed bronchopneumonia and the blood culture was positive for Salmonella typhi. Ocular examination revealed bilateral panophthalmitis, which was confirmed on ultrasound B scan and MRI of the orbits. The patient was started on intravenous antibiotics and a core vitrectomy was performed in the right eye along with intravitreal antibiotic injection. Bronchopneumonia, proptosis and periorbital edema resolved with systemic antibiotic therapy but the patient developed bilateral phthisis bulbi. This is the first case report of metastatic, bilateral panophthalmitis caused by Salmonella typhi.

Acute Intermittent Porphyria in a Kumhar community of Western Rajasthan.

OBJECTIVE: To know the current magnitude of the occurrence of Acute Intermittent Porphyria in Kumhar community of a part of Western Rajasthan. MATERIAL AND METHODS: This is a cross sectional study of rural community of Kumhars of Bikaner district of Western Rajasthan. The households of kumhar community were approached. Besides recording other information and examination details, their urine samples were subjected to Watson-Schwartz Test. RESULT: 1237 subjects out of a total of 2385 kumhar population distributed among 20 randomly selected villages of Bikaner district could be studied. The prevalence of AIP was estimated to be 1.16%. (CI=0.012 +/- 0.0005), showing higher prevalence than the earlier reported studies. The cases exhibited varied symptomatology. Overall preponderance was in favor of females (2:1) and majority of cases (38.9%) were found in the age group of 20-29 years. Average age of manifestation was 24.5 +/- 4.8 years. A follow up was also done to know the disease consequences, if any. CONCLUSIONS: The study finds higher prevalence of the disease and as such warrants a need for generating awareness among the families of cases in the specific caste group in the study area for early detection and better management of the disease.

Temperature affects the results of the glutaraldehyde test in the diagnosis of pulmonary tuberculosis.

SETTING: Subjects attending the District Tuberculosis Clinic and a Teaching Hospital in Jodhpur were studied at the Desert Medicine Research Centre, Jodhpur. OBJECTIVES: To confirm the effect of temperature on the results of the blood glutaraldehyde test (GT) and to examine the sensitivity and specificity of the restandardised test procedure. DESIGN: Blood glutaraldehyde gelification time (BGGT) was compared, in the same blood samples, at 19, 22 and 25 degrees C and after storage at 1) room temperature and at 2) 2-8 degrees C for 3-5 h, using the paired t-test. After restandardisation of the procedure, the GT was carried out on 88 sputum culture-positive cases with pulmonary tuberculosis (PTB) and 182 controls. The technician was blinded to patient information. RESULTS: BGGT significantly varied with the temperature of the water bath and the temperature at which blood samples were stored before testing. When the test was carried out in the water bath at 22 degrees C after storing blood for 3-5 h at 2-8 degrees C, as per the restandardised procedure, the specificity of GT was 96.2% (95 %CI 93.36-98.95) and the sensitivity was 84.1% (95%CI 76.45-91.73). CONCLUSION: Restandardised GT is a reliable, simple, easy, rapid, inexpensive and user-friendly test for diagnosis of PTB which does not require sophisticated laboratory equipment.

Intracellular and juxtacellular staining with biocytin.

Many physiological studies require microscopic examination of the recorded neuron for identification. This unit describes how intracellular and extracellular recording can be combined with single-neuron staining to enable sequential physiological and morphological studies.

Effects of stimulus duration on neuronal response properties in the somatosensory cortex of the star-nosed mole.

Star-nosed moles have a series of mechanosensory appendages surrounding each nostril. Each appendage is covered with sensory organs (Eimer's organs) containing both rapidly adapting and slowly adapting mechanoreceptors and each appendage is represented in primary somatosensory cortex (S1) by a single cortical module. When the skin surface of an appendage is depressed, neurons in the corresponding module in S1 respond in either a transient or sustained fashion. The aim of this study was to characterize and compare the responses of these two classes of neurons to both short (5 or 20 ms) and long (500 ms) mechanosensory stimulation. Activity from neurons in the representation of appendage 11, the somatosensory fovea, was recorded while delivering mechanosensory stimuli to the corresponding skin surface. Transient and sustained neurons had different levels of spontaneous activity and different responses to both short and long mechanosensory stimulation. Neurons with sustained responses had a significantly higher spontaneous firing rate than neurons with transient responses. Transient neurons responded to a 5 ms stimulus with excitation followed by suppression of discharge whereas sustained neurons did not exhibit post-excitatory suppression. Rather, responses of sustained neurons to 5 ms stimuli lasted several hundred milliseconds. Consequently sustained responses contained significantly more spikes than transient responses. These experiments suggest contact to the appendages causes two distinct firing patterns in cortex regardless of the duration of the stimulus. The sustained and transient responses could reflect either the activity of fundamentally different classes of neurons or activity in distinct subcortical and cortical networks.

Temporal organization of multi-whisker contact in rats.

Previous work has established that during exploration and discrimination, rats move their whiskers at frequencies between 6 and 12 Hz and that whisking frequency changes during contact. One critical component of any tactile system is contact. In the rat whisker system, such contacts may involve one or more vibrissa in the whisker array and contact duration of each whisker may vary over a considerable range, depending upon the behavioral context. However, little is known about the variables controlling contact duration or about the temporal relationships among contacts by adjacent whiskers. To address these issues head fixed rats were trained to touch a piezo-contact-sensor with the shaft of their whiskers (Bermejo and Zeigler, Somatosens Mot Res 17: 373-377, 2000). During the task, whisker movements and contacts were monitored with a high-speed camera at 500 frames/s and stored on videotape. To facilitate analysis, animals had their whiskers selectively trimmed. Data are reported from animals with C1 & C2, D1 & D2, or Arc2 (E2, D2, C2, B2) whiskers intact. For both row and arc animals, when just a single whisker touched the sensor the duration of contact was significantly shorter than when multiple whiskers made contact. When multiple whiskers made contact, onset was rarely simultaneous. Furthermore, in row-intact animals, contact progressed in an orderly fashion such that the rostral whisker in a row made contact first followed 24 ms (SE = 1.9 ms) later by the caudal whisker. When contact reversed the caudal whisker lifted off first, followed by the rostral whisker. Thus, the order in which whiskers touch an object regulates contact duration: the first whisker to touch the sensor stays in contact longer than any other whisker. The temporal discharge properties of neurons in the trigeminal system are expected to reflect position of whiskers on the nose.

Cortical barrel field ablation and unconditioned whisking kinematics.

The effects of "barrel cortex" ablation upon the biometrics of "exploratory" whisking were examined in three head-fixed rats which had previously sustained unilateral ablation of the left cortical "barrel field" under electrophysiological control. Unconditioned movements of a pair of bilaterally homologous whiskers (C-1, Right, Left) were monitored, optoelectronically, with other whiskers present. Whisking movements on the intact and ablated side were analyzed with respect to kinematics (protraction amplitude and velocity) whisking frequency and phase relationships between whisking movement on the two sides of the face. Histological analysis confirmed complete removal of S-1 "barrel cortex". In normal animals whisking movements have a characteristic rhythm (6-9 Hz), and protractions on the two sides of the face tend to be both synchronous and of very similar amplitudes. In the lesioned animals, whisking frequency was unchanged and whisking movements remained bilaterally synchronous. However, there was a significant difference between the amplitude of Right and Left whisker movements which was evident many months postoperatively. Our results suggest that the deficits in vibrissa-mediated tactile discrimination reported after "barrel" field ablation may reflect an impairment in the animal's ability to modulate whisking parameters on the two sides of the face to meet the functional requirements of a discriminative whisking task. The effects upon whisking amplitude seen after unilateral barrel field ablation are consistent with a model in which the activity of a whisking Central Pattern Generator is modulated by descending inputs to achieve sensorimotor control of whisking movement parameters.

Malaria outbreak in the Indira Gandhi Nahar Pariyojna command area in Jaisalmer district, Thar Desert, India.

A focal outbreak of malaria occurred in the villages situated close to the main Indira Gandhi canal near Ramgarh in Jaisalmer district, western Rajasthan. Stagnation of water over a month's period in the main canal as well as long standing rain water in the form of expansive lakes near these villages formed vast breeding grounds for the vectors like Anopheles culicifacies, along with A. stephensi already breeding in the 'tanka' and 'beri' in the epidemichit villages. Rapid mass blood surveys along with other entomological and parasitological investigations were conducted in four of the ten affected villages, viz., Seuva, Raghwa, Raimala and Sadhna. A total of 992 specimens belonging to four vector species were sampled, namely, A. stephensi (47.4%), A. culicifacies (41.0%), A. subpictus (11.2%) and A. annularis (0.4%). Epidemiologically, about one-fourth of the examined persons were positive (SPR 25.5%), although Plasmodium falciparum dominated the parasitaemia (49.5%). Available data are indicative of changed malariological scenario in the Indira Gandhi Nahar Pariyojna command area, where epidemics are regular features every year.