bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of Itraconazole with Broad-Spectrum
In Vitro
Antienterovirus Activity That Targets Nonstructural Protein 3A
Authors: Gao Qianqian , Yuan Shilin , Zhang Chao , Wang Ying , Wang Yizhuo , He Guimei , Zhang Shuyi , Altmeyer Ralf , Zou Gang
Published: February 2015

There is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections, which remain a substantial threat to public health. To discover inhibitors that can be immediately repurposed for treatment of enterovirus infections, we developed a high-throughput screening assay that measures the cytopathic effect induced by enterovirus 71 (EV71) to screen an FDA-approved drug library. Itraconazole (ITZ), a triazole antifungal agent, was identified as an effective inhibitor of EV71 replication in the low-micromolar range (50% effective concentrations [EC
50
s], 1.15 μM). Besides EV71, the compound also inhibited other enteroviruses, including coxsackievirus A16, coxsackievirus B3, poliovirus 1, and enterovirus 68. Study of the mechanism of action by time-of-addition assay and transient-replicon assay revealed that ITZ targeted a step involved in RNA replication or polyprotein processing. We found that the mutations (G5213U and U5286C) conferring the resistance to the compound were in nonstructural protein 3A, and we confirmed the target amino acid substitutions (3A V51L and 3A V75A) using a reverse genetic approach. Interestingly, posaconazole, a new oral azole with a molecular structure similar to that of ITZ, also exhibited anti-EV71 activity. Moreover, ITZ-resistant viruses do not exhibit cross-resistance to posaconazole or the enviroxime-like compound GW5074, which also targets the 3A region, indicating that they may target a specific site(s) in viral genome. Although the protective activity of ITZ or posaconazole (alone or in combination with other antivirals) remains to be assessed in animal models, our findings may represent an opportunity to develop therapeutic interventions for enterovirus infection.
Alga-Produced Malaria Transmission-Blocking Vaccine Candidate Pfs25 Formulated with a Human Use-Compatible Potent Adjuvant Induces High-Affinity Antibodies That Block Plasmodium falciparum Infection of Mosquitoes
Authors: Patra Kailash P. , Li Fengwu , Carter Darrick , Gregory James A. , Baga Sheyenne , Reed Steven G. , Mayfield Stephen P. , Vinetz Joseph M.
Published: February 2015

A vaccine to prevent the transmission of malaria parasites from infected humans to mosquitoes is an important component for the elimination of malaria in the 21st century, yet it remains neglected as a priority of malaria vaccine development. The lead candidate for
Plasmodium falciparum
transmission-blocking vaccine development, Pfs25, is a sexual stage surface protein that has been produced for vaccine testing in a variety of heterologous expression systems. Any realistic malaria vaccine will need to optimize proper folding balanced against cost of production, yield, and potentially reactogenic contaminants. Here
Chlamydomonas reinhardtii
microalga-produced recombinant Pfs25 protein was formulated with four different human-compatible adjuvants (alum, Toll-like receptor 4 [TLR-4] agonist glucopyranosal lipid A [GLA] plus alum, squalene–oil-in-water emulsion, and GLA plus squalene–oil-in-water emulsion) and compared for their ability to induce malaria transmission-blocking antibodies. Alga-produced recombinant Pfs25 plus GLA plus squalene–oil-in-water adjuvant induced the highest titer and avidity in IgG antibodies, measured using alga-produced recombinant Pfs25 as the enzyme-linked immunosorbent assay (ELISA) antigen. These antibodies specifically reacted with the surface of
P. falciparum
macrogametes and zygotes and effectively prevented parasites from developing within the mosquito vector in standard membrane feeding assays. Alga-produced Pfs25 in combination with a human-compatible adjuvant composed of a TLR-4 agonist in a squalene–oil-in-water emulsion is an attractive new vaccine candidate that merits head-to-head comparison with other modalities of vaccine production and administration.
Staphylococcus aureus Adapts to Oxidative Stress by Producing H
2
O
2
-Resistant Small-Colony Variants via the SOS Response
Authors: Painter Kimberley L. , Strange Elizabeth , Parkhill Julian , Bamford Kathleen B. , Armstrong-James Darius , Edwards Andrew M.
Published: February 2015

The development of chronic and recurrent
Staphylococcus aureus
infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of
S. aureus
to sublethal concentrations of H
2
O
2
leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H
2
O
2
exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the
S. aureus
population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H
2
O
2
also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H
2
O
2
than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H
2
O
2
. Taken together, these data reveal a mechanism by which
S. aureus
adapts to oxidative stress via the production of a subpopulation of H
2
O
2
-resistant SCVs with enhanced catalase production.
C-Reactive Protein Protects Mice against Pneumococcal Infection via Both Phosphocholine-Dependent and Phosphocholine-Independent Mechanisms
Authors: Gang Toh B. , Hanley Gregory A. , Agrawal Alok
Published: February 2015

The mechanism of action of C-reactive protein (CRP) in protecting mice against lethalStreptococcus pneumoniaeinfection is unknown. The involvement of the phosphocholine (PCh)-binding property of CRP in its antipneumococcal function previously has been explored twice, with conflicting results. In this study, using three different intravenous sepsis mouse models, we investigated the role of the PCh-binding property of CRP by employing a CRP mutant incapable of binding to PCh. The ability of wild-type CRP to protect mice against infection was found to differ in the three models; the protective ability of wild-type CRP decreased when the severity of infection was increased, as determined by measuring mortality and bacteremia. In the first animal model, in which we used 25 μg of CRP and 107CFU of pneumococci, both wild-type and mutant CRP protected mice against infection, suggesting that the protection was independent of the PCh-binding activity of CRP. In the second model, in which we used 25 μg of CRP and 5 × 107CFU of pneumococci, mutant CRP was not protective while wild-type CRP was, suggesting that the protection was dependent on the PCh-binding activity of CRP. In the third model, in which we used 150 μg of CRP and 107CFU of pneumococci, mutant CRP was as protective as wild-type CRP, again indicating that the protection was independent of the PCh-binding activity of CRP. We conclude that both PCh-dependent and PCh-independent mechanisms are involved in the CRP-mediated decrease in bacteremia and the resulting protection of mice against pneumococcal infection.
Disruption of the Membrane Nuclease Gene (MBOVPG45_0215) of Mycoplasma bovis Greatly Reduces Cellular Nuclease Activity
Authors: Sharma Shukriti , Tivendale Kelly A. , Markham Philip F. , Browning Glenn F.
Published: February 2015

Although the complete genome sequences of three strains ofMycoplasma bovisare available, few studies have examined gene function in this important pathogen. Mycoplasmas lack the biosynthetic machinery for thede novosynthesis of nucleic acid precursors, so nucleases are likely to be essential for them to acquire nucleotide precursors. Three putative membrane nucleases have been annotated in the genome ofM. bovisstrain PG45, MBOVPG45_0089 and MBOVPG45_0310, both of which have the thermonuclease (TNASE_3) functional domain, and MBOVPG45_0215 (mnuA), which has an exonuclease/endonuclease/phosphatase domain. While previous studies have demonstrated the function of TNASE_3 domain nucleases in several mycoplasmas, quantitative comparisons of the contributions of different nucleases to cellular nuclease activity have been lacking. Mapping of a library of 319 transposon mutants ofM. bovisPG45 by direct genome sequencing identified mutants with insertions in MBOVPG45_0310 (the Δ0310 mutant) and MBOVPG45_0215 (the Δ0215 mutant). In this study, the detection of the product of MBOVPG45_0215 in the Triton X-114 fraction ofM. boviscell lysates, its cell surface exposure, and its predicted signal peptide suggested that it is a surface-exposed lipoprotein nuclease. Comparison of a ΔmnuAmutant with wild-typeM. bovison native and denatured DNA gels and in digestion assays using double-stranded phage λ DNA and closed circular plasmid DNA demonstrated that inactivation of this gene abolishes most of the cellular exonuclease and endonuclease activity ofM. bovis. This activity could be fully restored by complementation with the wild-typemnuAgene, demonstrating that MnuA is the major cellular nuclease ofM. bovis.

IMPORTANCENucleases are thought to be important contributors to virulence and crucial for the maintenance of a nutritional supply of nucleotides in mycoplasmas that are pathogenic in animals. This study demonstrates for the first time that of the three annotated cell surface nuclease genes in an important pathogenic mycoplasma, the homologue of the thermostable nuclease identified in Gram-positive bacteria is responsible for the majority of the nuclease activity detectablein vitro.
Evolution of insulin resistance in coronary artery disease patients on four different pharmacological therapies
Authors: Piédrola Gonzalo , Novo Enrique , Serrano-Gotarredona Joaquín , de Teresa Maria Luisa , García-Robles Rafael
Published: February 2015

The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) × 103. A second insulin suppression test was performed after 6 months' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients.

There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.
Gangrenous cystitis: a rare cause of colovesical fistula
Authors: Raza A , Balsitis M , Hosie K B
Published: February 2015

A case of gangrenous cystitis presenting as a colovesical fistula in an elderly woman is described. The literature on this rare condition is reviewed.
Red-man syndrome after vancomycin: potential cross-reactivity with teicoplanin
Authors: Khurana C , de Belder M A
Published: February 2015

We report a patient with infective endocarditis who developed a severe form of Red-man syndrome after vancomycin. On substituting the antibiotic to teicoplanin, the patient went on to develop a dramatic pyrexia which settled only after the teicoplanin was discontinued. This suggested that there may be an element of cross-reactivity between teicoplanin and vancomycin in such patients and that teicoplanin may not be the most appropriate substitute in all cases of vancomycin-induced Red-man syndrome.
Unilateral gestational macromastia − an unusual presentation of a rare disorder
Authors: Zargar Abdul Hamid , Laway Bashir Ahmad , Masoodi Shariq Rashid , Chowdri Nisar Ahmad , Bashir Mir Iftikhar , Wani Arshad Iqbal
Published: February 2015

Macromastia (mammary gigantism) is an uncommon clinical entity. Macromastia occurring during pregnancy (gestational macromastia) is rare. A case of unilateral gestational macromastia is reported which required reduction mammoplasty. We documented hyperprolactinaemia in the patient. This case report is particularly interesting because, to our knowledge, no such case has previously been reported.
Modern management of eclampsia
Authors: Salha Osama , Walker James J
Published: February 2015

Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality and morbidity. Despite being recognised since antiquity, consistent management practices are still lacking. Given that the aim of good care is to prevent seizures, it is disappointing that in the majority of cases the first eclamptic convulsion occurs after admission to hospital. This indicates that either the women who are likely to have a convulsion were not identified accurately, or the treatment given was ineffective. The answer to poor management of eclampsia lies in better education and training of all obstetricians, anaesthetists, midwives, and general practitioners in the diagnosis and treatment of severe pre-eclampsia and eclampsia. Protocols for the management of fluid balance, antihypertensive and anticonvulsant therapies should be available and reviewed regularly. The universal adoption of such guidelines in all obstetric units would substantially reduce elements of substandard care which have repeatedly been identified in the triennial reports of the confidential enquiries into maternal deaths in the UK.
Physician attitudes and behaviour regarding erectile dysfunction in at-risk patients from a rural community
Authors: Perttula Eric
Published: February 2015

Erectile dysfunction affects many men in the United States. A 34% prevalence is estimated among male family practice patients. It is associated with a loss of self-image, self-confidence, and even chronic anger. Several risk factors increases the risk of erectile dysfunction. Prevalence is increased by 20–40% in patients with diabetes, hypertension, and those over 65 years old. While erectile dysfunction is generally acknowledged as an important health problem, misconceptions remain as to the need for clinician-initiated discussion regarding the issue. A retrospective chart review of patients at three health clinics in a predominately rural area was conducted. Subjects (n=102) were those at risk of erectile dysfunction who had undergone a complete physical exam between October 1995 and December 1996. All physician encounters were examined for documentation of physician inquiry about erectile dysfunction. A survey of physician perceptions on initiating discussions of erectile dysfunction was also conducted. Physician-initiated discussion of erectile dysfunction was documented in 17% of patients with hypertension, 18% with diabetes mellitus, and 30% of patients > 65 years. The physician survey (11 respondents) showed 27% reported asking all male patients about erectile dysfunction at routine physical, while 45% reported asking 80% of their male patients. A ‘lack of time’ or belief that the ‘patient will initiate discussions’ was cited by several practitioners as reasons why inquiries were not initiated. All physicians in the study agreed that sexual function is an integral part of overall health. They either overestimated the percentage of patients asked about erectile dysfunction or they had not documented results consistently.
Carcinoid-associated ectopic ACTH syndrome with variable response to octreotide
Authors: Gill Geoffrey V , Yong Alice , Power Eileen , Ramage John
Published: February 2015

The case is presented of a 31-year-old woman who developed florid clinical and biochemical Cushing's syndrome due to metastatic hepatic carcinoid tumour from a probable pancreatic primary. Hypercortisolaemia was controlled with metyrapone and ketoconazole, but high doses of octreotide failed to affect plasma cortisol and urinary 5-hyroxyindole acetic acid (5HIAA) levels, or prevent rapid tumour growth. Hepatic polystyrene embolisation failed, and she was treated by liver transplantation with initial excellent results, and normalisation of cortisol and 5HIAA levels. Ten months later, however, she relapsed with bony and pelvic tumour recurrence, and high and symptomatic levels of cortisol and 5HIAA. At this time, octreotide in similar doses to those used previously appeared to normalise her biochemically, although she died soon after. This variable responsiveness to octreotide could be related to somatostatin receptor changes, or cyclical tumour secretion patterns.
Primary antibody deficiency and Crohn's disease
Authors: Conlong P , Rees Wynne , Shaffer J L , Nicholson David , Jewell Derek , Heaney Mansel , Jones Aled , Snowden Neil
Published: February 2015

Five patients with primary antibody deficiency were investigated because of intermittent but persistent diarrhoea of several years duration despite immunoglobulin replacement therapy. We found no evidence of Giardia lambia or other intestinal pathogens to explain their gastrointestinal symptoms. All five had definite radiological evidence of small bowel Crohn's disease and three had histological specimens available with abnormalities consistent with Crohn's disease. One patient had a non-caseating granuloma in an oral ulcer. A second patient with stricturing disease in the small bowel had a mucosal inflammatory infiltrate with non-caseating granulomas. A third had transmural inflammation but no granulomas. All five patents were diagnosed as having Crohn's disease and have responded symptomatically to steroid therapy.
Evaluation of renal function in elderly heart failure patients on ACE inhibitors
Authors: Jolobe O M P
Published: February 2015

A total of 187 heart failure patients aged 65–92 years, with pretreatment serum creatinine levels below 200 μmol/l, were monitored for more than 12 months on angiotensin-converting enzyme (ACE) inhibitor therapy. Optimal ACE inhibitor dosage was found in 27% of patients, while a significant deterioration in renal function, characterised by >20% increase in serum creatinine to >200 μmol/l, occurred in 25 patients. This was most closely attributable to ACE inhibitor treatment per se (implying co-existence of bilateral renal artery stenosis) in only four cases, including one in whom renal deterioration was reproducible on inadvertent rechallenge. In the other 21, renal deterioration was attributable to diuretic-related blood volume depletion (two cases), nonsteroidal anti-inflammatory drugs (two cases), obstructive uropathy (two cases), preterminal renal shutdown (two cases), and the interaction between diuretic and ACE inhibitor dosage (including long-acting vs short-acting drugs) (13 cases). This study could serve as the basis for future comparisons of ACE-inhibitor-related renal deterioration when the entry requirement is optimal ACE inhibitor dosage.
Lobular carcinoma-in-situ within a fibroadenoma of the breast
Authors: Shah Ajay K , Pathak Ranganath , Banerjee Subhendra N , Kaul Ashutosh , Niazi Masooma , Girishkumar Hanasoge T
Published: February 2015

We present a case of an in-situ lobular carcinoma within an otherwise benign fibroadenoma in a 45-year-old woman.
Induction for senior house officers. Part I: The hospital programme
Authors: Ward Simon J , Stanley Paula
Published: February 2015

The study was set up to examine how an induction programme can be designed to meet the needs and expectations of senior house officers (SHOs) beginning a new post in a hospital. A total of 63 SHOs, in five hospitals in the Anglia region, participated in standardised structured interviews up to 3 months after starting their post, by sorting a list of 38 possible induction topics in order of priority. Trainees' early induction needs were found to centre on day-one service activities, ie, information that enables them to undertake their service work efficiently and effectively, is particularly valued and required early. Information related to clinical education and training is also valued, but many trainees prefer it to be provided after they have been in post for a week or two. Much induction information can also be effectively conveyed in writing, with little or no need for additional formal presentation. We conclude that first-day induction programmes which strive to satisfy the range of trainee needs in one session fail to take account of the different priorities that trainees attach to induction information. Trainees do not want all information at once. Information of prime concern to clinical tutors, namely education, training and generic skills, is generally favoured after a week or two. To ensure that trainees' hospital induction needs are met in an efficient and effective way, programmes must be flexible and timely, and supported by comprehensive written information.
Pentazocine-induced fibromyositis and contracture
Authors: Das C P , Thussu A , Prabhakar S , Banerjee A K
Published: February 2015

We report a case of myopathy, accompanied by widespread contractures predominantly involving the elbow and knee joints, following long-standing pentazocine abuse.
Spontaneous rupture of a saphenous vein graft
Authors: Davey Patrick , Gwilt David , Forfar Colin
Published: February 2015

We present a case of spontaneous rupture of a right coronary bypass vein graft in a 57-year-old woman 10 years after coronary by-pass surgery. Although rare, this diagnosis should be considered in such patients presenting with appropriate symptoms.
Methods of obtaining peripheral venous access in difficult situations
Authors: Mbamalu David , Banerjee Ashis
Published: February 2015

Peripheral venous access is frequently required in the hospital environment. This can occasionally be difficult to obtain. We have reviewed the pertinent literature and propose a structured algorithmic approach to reduce patient discomfort and to minimise the time involved in securing venous access.
Hypersensitivity pneumonitis associated with co-proxamol (paracetamol + dextropropoxyphene) therapy
Authors: Matusiewicz S P , Wallace W A H , Crompton G K
Published: February 2015

A 61-year-old man developed hypersensitivity pneumonitis and skin rash in close association with taking co-proxamol. These problems occurred in spite of being treated with prednisolone 40 mg daily (20 mg daily at the time of presentation) for assumed cranial arteritis. A therapeutic challenge with paracetamol was negative and the patient continues to take this drug. It seems likely that this patient's rash and hypersensitivity pneumonitis was caused by dextropropoxyphene. Dextropropoxyphene has not been reported previously as a cause of hypersensitivity pneumonitis.
Hereditary hypophosphataemic rickets: report of a family from the Indian subcontinent
Authors: Zargar Abdul Hamid , Laway Bashir Ahmad , Masoodi Shariq Rashid , Hakim Fayaz Ahmad , Wani Arshad Iqbal , Bashir Mir Iftikhar , Mithal Ambrish
Published: February 2015

Nutritional deficiency continues to be an important cause of rickets in the underdeveloped and developing parts of the world. In the western hemisphere, predominantly non-nutritional forms of rickets and osteomalacia are now seen. In this report we discuss a family with X-linked hypophosphataemic rickets from the Kashmir region of the Indian subcontinent (which is an uncommon entity here).
Lambert-Eaton myasthenic syndrome
Authors: Seneviratne Udaya , de Silva Rajith
Published: February 2015

The Lambert-Eaton myasthenic syndrome is a neuromuscular disorder characterised by defective neurotransmitter release at autonomic neurones and presynaptic terminals of the neuromuscular junction. It is caused by an IgG autoantibody formed against especially the P/Q type of voltage-gated calcium channels (VGCC) which is an essential component of the mechanism of neurotransmitter release. Many patients have an associated small cell carcinoma of the lung which appears to provide the antigenic stimulus for antibody production, although there is another group with no underlying malignancy. Both groups show an association with immunological disorders. Assay of VGCC antibody titres and electrophysiological tests help to differentiate Lambert-Eaton myasthenic syndrome from other disorders of the neuromuscular junction. Several drugs and therapeutic interventions capable of producing significant clinical improvement are currently available. Patients should also be investigated for underlying tumours, the specific treatment of which can result in remission or amelioration of symptoms.
Ergotism related to a single dose of ergotamine tartrate in an AIDS patient treated with ritonavir
Authors: Blanche P , Rigolet A , Gombert B , Ginsburg C , Salmon D , Sicard D
Published: February 2015

We report a rare case of ergotism related to a single dose of ergotamine tartrate in a man with AIDS being treated with ritonavir. He was treated with a prostacyclin analogue and made a complete recovery.
A non-contact complete knee dislocation with popliteal artery disruption, a rare martial arts injury
Authors: Viswanath Y K S , Rogers I M
Published: February 2015

Complete knee dislocation is a rare injury and an associated incidence of popliteal artery damage ranges from 16–60% of cases. It occurs commonly in road traffic accidents and in high velocity trauma where significant contact remains as the usual mode of injury. We describe a rare case of non-contact knee dislocation with popliteal artery injury sustained while practising Aikido, a type of martial art. This patient successfully underwent closed reduction of the knee with an emergency vein bypass graft. Similar injury in association with Aikido has not been described in the English literature previously. Various martial art injuries are briefly discussed and safety recommendations made.
General hospital services for deliberate self-poisoning: an expensive road to nowhere?
Authors: Kapur Navneet , House Allan , Creed Francis , Feldman Eleanor , Friedman Trevor , Guthrie Elspeth
Published: February 2015

This study was designed to investigate the clinical and economic aspects of deliberate self-poisoning services in four teaching hospitals in Leeds, Leicester, Manchester and Nottingham. We investigated the management of the current self-harm episode, including direct in-hospital costs, in 456 individuals who presented to hospital on a total of 477 occasions with deliberate self-poisoning during a 4-week period in 1996. Fewer than half of the patients received specialist psychosocial assessment or follow-up. Patients were more likely to receive an assessment if they were already in contact with psychiatric services, had a history of previous overdoses, if they presented during working hours, or if they lived near the hospital. Patients who were admitted were nearly twice as likely to receive specialist assessment, and those who received a specialist assessment were nearly three times as likely to be offered follow-up. In-patient days and days on the intensive care unit accounted for 47% and 8% of the total costs, respectively. This study suggests that general hospital services are disorganised, with evidence of inequitable access to specialist assessment and aftercare. This state of affairs cannot be justified on financial or clinical grounds.
Recurrent proptotic diplopia due to congestive expansion of cavernous haemangioma with relapsing right-sided cardiac failure
Authors: O'Mahony Denis , O'Neill Eamon
Published: February 2015

A 75-year-old man with a recent history of pulmonary embolism, presented with collapse followed by a gran mal seizure and right-sided non-pulsatile proptosis. On recovery, he had diplopia on lateral and upward gaze and signs of congestive cardiac failure. Further pulmonary embolism was proven by lung scintigraphy. Computed tomography of his orbits confirmed a contrast-enhancing space-occupying lesion of the medial wall of the right orbit, with no intracranial abnormality. The patient was investigated for metastatic tumour as a possible cause of the space-occupying lesion and the unprovoked thromboembolic event, but no evidence of malignancy was found. The orbital lesion was not biopsied because of the risk of bleeding from anticoagulation. Three weeks later, the patient re-presented with recurrent cardiac failure, proptosis, and diplopia. A transorbital ultrasound confirmed an encapsulated, well-defined vascular lesion, with typical appearances and Doppler flow characteristics of a cavernous haemangioma. Diuretic therapy abolished the proptosis and diplopia in tandem with relief of the cardiac failure. This is the first description of recurrent proptosis with diplopia due to recurrent congestive expansion of an orbital cavernous haemangioma.
High-dose intravenous glucagon in severe tricyclic poisoning
Authors: Sensky Penelope R , Olczak Stephen A
Published: February 2015

A case of dothiepin poisoning complicated by cardiogenic shock is described. Hypotension was resistant to conventional inotropes but responded rapidly to high-dose intravenous glucagon. Glucagon should be considered as a useful therapeutic positive inotrope and a potentially anti-arrhythmic agent in severe tricyclic antidepressant overdose.
Management of acute myocardial infarction in general medical wards in Sri Lanka
Authors: Constantine G R , Herath J I P , Chang A A P T , Suganthan P , Hewamane B S L , Thenabadu P N
Published: February 2015

The study was designed to evaluate the management of acute myocardial infarction in the general medical wards of the National Hospital of Sri Lanka. All patients with acute myocardial infarction admitted from September 1996 to August 1997, were evaluated with regard to the time delay in admission and drug treatment. The facilities for monitoring and resuscitation were also assessed. A total of 259 patients were included in the study, 173 males and 86 females. The median time delay from the onset of the pain to admission at the out-patients department was 12 hours and that between out-patients department admission and ward admission was 20 minutes. The median delay in obtaining a 12-lead electrocardiogram when the patient was in the ward was 90 minutes. Review of the data showed that thrombolytic therapy, beta-blockers and angiotensin-converting enzyme inhibitors are underused. Complications were common. All the medical wards had adequate monitoring and resuscitation facilities. With adequate training of doctors and the availability of specialised cardiac nurses, thrombolytic therapy can be used effectively in medical wards.
Mesenteric infarction due to combined protein C deficiency and prothrombin 20210 defects
Authors: Mainwaring C J , Makris M , Thomas W E G , Hampton K K , Preston F E
Published: February 2015

The prothrombin gene mutation, 20210A, a guanine to adenine substitution at nucleotide position 20210, has recently been described as an additional risk factor for venous thromboembolic disease. We describe the case of a patient with combined heterozygous prothrombin 20210A mutation and type 1 protein C deficiency who presented with massive mesenteric venous infarction of his small bowel and survived following the use of protein C concentrate and extensive small bowel resection.
Analysis and Design of a Precise Voltage Buffer
Authors: Khaneshan Tohid Moradi , Nematzade Mojde , Hadidi Khayrollah , Khoei Abdollah
Published: February 2015

An open loop voltage buffer with an exact unity gain using a positive local feedback technique with a conventional source follower is proposed. Stability of the buffer is determined by evaluating the location of the poles and zeros and its linearity is studied using Volterra series expansion. The proposed buffer is laid out in 0.35-μm standard CMOS technology. Post layout simulations demonstrate that the buffer gain is close to unity with less than 0.2% error. The power consumption is 10 mw from a 3.3 V power supply and the achieved total harmonic distortion is -78 dB for a 10 MHz input frequency. Also Monte-Carlo simulations are carried out to investigate effects of random mismatches on the circuit operation.
Deterministic Linkage as a Preceding Filter for Other Record Linkage Methods
Authors: Sariyar M. , Borg A.
Published: February 2015

Deterministic record linkage (RL) is frequently regarded as a rival to more sophisticated strategies like probabilistic RL. We investigate the effect of combining deterministic linkage with other linkage techniques. For this task, we use a simple deterministic linkage strategy as a preceding filter: a data pair is classified as ‘match' if all values of attributes considered agree exactly, otherwise as ‘nonmatch'. This strategy is separately combined with two probabilistic RL methods based on the Fellegi–Sunter model and with two classification tree methods (CART and Bagging). An empirical comparison was conducted on two real data sets. We used four different partitions into training data and test data to increase the validity of the results. In almost all cases, application of deterministic linkage as a preceding filter leads to better results compared to the omission of such a pre-filter, and overall classification trees exhibited best results. On all data sets, probabilistic RL only profited from deterministic linkage when the underlying probabilities were estimated before applying deterministic linkage. When using a pre-filter for subtracting definite cases, the underlying population of data pairs changes. It is crucial to take this into account for model-based probabilistic RL.
Runtime Optimization of System Utility with Variable Hardware
Authors: Martin Paul , Wanner Lucas , Srivastava Mani
Published: February 2015

Increasing hardware variability in newer integrated circuit fabrication technologies has caused corresponding power variations on a large scale. These variations are particularly exaggerated for idle power consumption, motivating the need to mitigate the effects of variability in systems whose operation is dominated by long idle states with periodic active states. In systems where computation is severely limited by anemic energy reserves and where a long overall system lifetime is desired, maximizing the quality of a given application subject to these constraints is both challenging and an important step toward achieving high-quality deployments. This work describes VaRTOS, an architecture and corresponding set of operating system abstractions that provide explicit treatment of both idle and active power variations for tasks running in real-time operating systems. Tasks in VaRTOS express elasticity by exposing individual
knobs
—shared variables that the operating system can tune to adjust task quality and, correspondingly, task power, maximizing application utility both on a per-task and on a system-wide basis. We provide results regarding online learning of instance-specific sleep power, active power, and task-level power expenditure on simulated hardware with demonstrated effects for several prototypical applications. Our results on networked sensing applications, which are representative of a broader category of applications that VaRTOS targets, show that VaRTOS can reduce variability-induced energy expenditure errors from over 70% in many cases to under 2% in most cases and under 5% in the worst case.
ACDC
Authors: Segarra Juan , Rodríguez Clemente , Gran Rubén , Aparicio Luis C. , Viñals Víctor
Published: February 2015

In multitasking real-time systems, the worst-case execution time (WCET) of each task and also the effects of interferences between tasks in the worst-case scenario need to be calculated. This is especially complex in the presence of data caches. In this article, we propose a small instruction-driven data cache (256 bytes) that effectively exploits locality. It works by preselecting a subset of memory instructions that will have data cache replacement permission. Selection of such instructions is based on data reuse theory. Since each selected memory instruction replaces its own data cache line, it prevents pollution and performance in tasks becomes independent of the size of the associated data structures. We have modeled several memory configurations using the Lock-MS WCET analysis method. Our results show that, on average, our data cache effectively services 88% of program data of the tested benchmarks. Such results double the worst-case performance of our tested multitasking experiments. In addition, in the worst case, they reach between 75% and 89% of the ideal case of always hitting in instruction and data caches. As well, we show that using partitioning on our proposed hardware only provides marginal benefits in worst-case performance, so using partitioning is discouraged. Finally, we study the viability of our proposal in the MiBench application suite by characterizing its data reuse, achieving hit ratios beyond 90% in most programs.
Classification Framework for Analysis and Modeling of Physically Induced Reliability Violations
Authors: Rodopoulos Dimitrios , Psychou Georgia , Sabry Mohamed M. , Catthoor Francky , Papanikolaou Antonis , Soudris Dimitrios , Noll Tobias G. , Atienza David
Published: February 2015

Technology downscaling is expected to amplify a variety of reliability concerns in future digital systems. A good understanding of reliability threats is crucial for the creation of efficient mitigation techniques. This survey performs a systematic classification of the state of the art on the analysis and modeling of such threats, which are caused by physical mechanisms to digital systems. The purpose of this article is to provide a classification tool that can aid with the navigation across the entire landscape of reliability analysis and modeling. A classification framework is constructed in a top-down fashion from complementary categories, each one addressing an approach on reliability analysis and modeling. In comparison to other classifications, the proposed methodology approaches the target research domain in a complete way, without suppressing hybrid works that fall under multiple categories. To substantiate the usability of the classification framework, representative works from the state of the art are mapped to each appropriate category and are briefly analyzed. Thus, research trends and opportunities for novel approaches can be identified.
A Review and Meta-Analysis of Multimodal Affect Detection Systems
Authors: D'mello Sidney K. , Kory Jacqueline
Published: February 2015

Affect detection is an important pattern recognition problem that has inspired researchers from several areas. The field is in need of a systematic review due to the recent influx of Multimodal (MM) affect detection systems that differ in several respects and sometimes yield incompatible results. This article provides such a survey via a quantitative review and meta-analysis of 90 peer-reviewed MM systems. The review indicated that the state of the art mainly consists of person-dependent models (62.2% of systems) that fuse audio and visual (55.6%) information to detect acted (52.2%) expressions of basic emotions and simple dimensions of arousal and valence (64.5%) with feature- (38.9%) and decision-level (35.6%) fusion techniques. However, there were also person-independent systems that considered additional modalities to detect nonbasic emotions and complex dimensions using model-level fusion techniques. The meta-analysis revealed that MM systems were consistently (85% of systems) more accurate than their best unimodal counterparts, with an average improvement of 9.83% (median of 6.60%). However, improvements were three times lower when systems were trained on natural (4.59%) versus acted data (12.7%). Importantly, MM accuracy could be accurately predicted (cross-validated
R
2
of 0.803) from unimodal accuracies and two system-level factors. Theoretical and applied implications and recommendations are discussed.
Constrained Community-Based Gene Regulatory Network Inference
Authors: Fioretto Ferdinando , Dovier Agostino , Pontelli Enrico
Published: February 2015

The problem of
gene regulatory network inference
is a major concern of systems biology. In recent years, a novel methodology has gained momentum, called
community network
approach. Community networks integrate predictions from individual methods in a “metapredictor,” in order to compose the advantages of different methods and soften individual limitations. This article proposes a novel methodology to integrate prediction ensembles using
constraint programming
, a declarative modeling and problem solving paradigm. Constraint programming naturally allows the modeling of dependencies among components of the problem as constraints, facilitating the integration and use of different forms of knowledge. The new paradigm, referred to as
constrained community network
, uses constraints to capture properties of the regulatory networks (e.g., topological properties) and to guide the integration of knowledge derived from different families of network predictions. The article experimentally shows the potential of this approach: The addition of biological constraints can offer significant improvements in prediction accuracy.
GreenLocs
Authors: Nguyen Nam Tuan , Zheng Rong , Liu Jie , Han Zhu
Published: February 2015

Understanding indoor mobility patterns of people is important in applications such as targeted advertisement, microclimate control, and delivery of anticipatory notifications. In this article, we devise GreenLocs, a nonparametric, profiling-free, yet lightweight and energy-efficient inference framework, to identify recurring and new places that mobile users visit indoor. Combining WiFi scans and accelerometer readings, GreenLocs can accurately decide a new place and a revisited place with just a few radio signal strength (RSS) samples. GreenLocs consists of three major building blocks, namely, missing data handling algorithms, a nonparametric Bayesian inference model, and a stopping rule, which significantly increases the energy efficiency of the system. GreenLocs is shown to be robust to signal variations and missing data through experimental evaluations using traces collected from mobile phones of different brands/models.
Towards Hardware-driven Design of Low-energy Algorithms for Data Analysis
Authors: Zliobaite Indre , Hollmen Jaakko , Koskinen Lauri , Teittinen Jukka
Published: February 2015

In the era of "big" data, data analysis algorithms need to be efficient. Traditionally researchers would tackle this problem by considering "small" data algorithms, and investigating how to make them computationally more efficient for big data applications. The main means to achieve computational efficiency would be to revise the necessity and order of subroutines, or to approximate calculations. This paper presents a viewpoint that in order to be able to cope with the new challenges of the growing digital universe, research needs to take a combined view towards data analysis algorithm design and hardware design, and discusses a potential research direction in taking an intreated approach in terms of algorithm design and hardware design. Analyzing how data mining algorithms operate at the elementary operations level can help do design more specialized and dedicated hardware, that, for instance, would be more energy efficient. In turn, understanding hardware design can help to develop more effective algorithms.
Unleashing the Power of Information Graphs
Authors: Lissandrini Matteo , Mottin Davide , Palpanas Themis , Papadimitriou Dimitra , Velegrakis Yannis
Published: February 2015

Information graphs are generic graphs that model different types of information through nodes and edges. Knowledge graphs are the most common type of information graphs in which nodes represent entities and edges represent relationships among them. In this paper, we argue that exploitation of information graphs can lead into novel query answering capabilities that go beyond the existing capabilities of keyword search, and focus on one of them, namely, exemplar queries. Exemplar queries is a recently introduced paradigm that treats a user query as an example from the desired result set. In this paper, we describe the foundations of exemplar queries and the significant role of information graphs, and we present several applications and relevant research directions.
Relationship between Body Mass Index and Tooth Decay in a Population of 3–6-Year-Old Children in Iran
Authors: Bafti Leila Shafie , Hashemipour Maryam Alsadat , Poureslami Hamidreza , Hoseinian Zeinab
Published: February 2015

The aim of the present study was to evaluate the relationship between BMI and tooth decay in a population of Iranian children. In this cross-sectional descriptive/analytical study, 1482 children were selected from kindergartens and preschool centers in Kerman, Iran. The children underwent examination of deciduous teeth (using the dmft index) after determination of height and weight for calculation of BMI. The relationship between BMI (after adjustment for age) and dmft was determined using Poisson’s regression model. The mean of dmft in children with normal BMI was 1.5-fold that in subjects with extra body weight. Age had a significant effect on dmft. In addition, dmft was higher in boys compared to girls. The results of the present study showed that caries rate in the deciduous teeth of 3–6-year-old children decreases with an increase in body weight.
Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation
Authors: Routy B. , Hoang J. , Gruber J.
Published: February 2015

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH) presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8) vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented.