Small Hand Research Articles

SPONTANEOUS REGRESSION OF SCLC WITH CONCURRENT ACID-FAST BACTERIUM INFECTION: A RARE CASE REPORT

SESSION TITLE: Lung Cancer 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Spontaneous remission (SR) is the phenomenon of cancer remission without medical treatment and is exceedingly rare for small cell lung carcinoma (SCLC). A few mechanisms explaining SR have been proposed: humoral mediated destruction, surgical trauma, and localized destruction. Here we present a case of SCLC spontaneous remission possibly due to activation of cell-mediated immunity attack on acid fast bacilli. CASE PRESENTATION: We present a 63 year old woman with a 80 pack year smoking history who underwent screening CT that showed a 1 cm nodule in the right upper lobe. Follow up PET/CT confirmed a 16 mm nodule. CT-guided biopsy showed a poorly differentiated carcinoma of small cells with neuroendocrine features, and she was diagnosed with SCLC stage Ia, cT1N0M0. MRI brain was negative for metastasis.Seven weeks later a right upper lobectomy was performed. The surgical pathology was negative for malignancy after reviewing 16 sections. It showed necrotizing granulomatous inflammation containing numerous acid fast organisms presumed to be Mycobacterium tuberculosis and she was started on RIPE therapy. Since the specimen had been placed in formalin, cultures were not obtainable. IGRA testing was negative. Follow up imaging at three months was negative for recurrence. DISCUSSION: A small handful of cases of SCLC spontaneous remission exist in literature (1). Seven cases were associated with antineuronal antibodies. Five cases had no suspected cause other than biopsy or surgery related trauma, that some hypothesize disrupted the cancer’s blood supply or architecture. In our case, a robust immune response against acid fast bacilli, especially when combined with needle biopsy micro-trauma, may induce spontaneous remission.Mycobacteria have shown some relationship with pulmonary malignancy: both cause fevers, dyspnea, hemoptysis, night sweats, and weight loss; both frequently appear as cavitary masses; and they are often misdiagnosed as the other. Usually chronic tuberculosis inflammation and scarring is thought to be a risk factor for developing pulmonary carcinoma, however this case suggests an acute infection may be protective. There are two explanations for this suggestion. First, Mycobacteria enhances a localized cell-mediated response--the same type of response previously shown to destroy SCLC (2). Second, Mycobacterium induces interferon release that promotes HLA-I expression on SCLC cells. The cells then present tumor specific antigen that renders them visible and vulnerable to cell-mediated immunity. Interestingly, clinical trials using Mycobacterium vaccae as an immunotherapeutic agent against SCLC showed some preliminary results (3). The act of biopsy likely facilitated this proposed immunological response resulting in spontaneous remission. CONCLUSIONS: Mycobacterial infection in conjunction with biopsy related trauma may be associated with spontaneous regression of SCLC. Reference #1: Horino T, Takao T, Yamamoto M, Geshi T, Hashimoto K. Spontaneous remission of small cell lung cancer: A case report and review in the literature. Lung Cancer. 2006;53(2):249-252. Reference #2: Traversari C, Meazza R, Coppolecchia M, Basso S, Verrecchia A, van der Bruggen P, Ardizzoni A, Gaggero A, Ferrini S. IFN-gamma gene transfer restores HLA-class I expression and MAGE-3 antigen presentation to CTL in HLA-deficient small cell lung cancer. Gene Therapy. 1997;4(10):1029-35. Reference #3: Assersohn L, Souberbielle BE, O'Brien ME, Archer CD, Mendes R, Bass R, Bromelow KV, Palmer RD, Bouilloux E, Kennard DA, Smith IE. A randomized pilot study of SRL172 (Mycobacterium vaccae) in patients with small cell lung cancer (SCLC) treated with chemotherapy. Clinical oncology. 2002;14(1):23-27. DISCLOSURES: No relevant relationships by William Hatch, source=Web Response No relevant relationships by Rajeev Narang, source=Web Response no disclosure on file for Gerard Voorhees

Optically Pumped Magnetometers for Magneto-Myography to Study the Innervation of the Hand.

The central nervous system exerts control over the activation of muscles via a dense network of nerve fibers targeting each individual muscle. There are numerous clinical situations where a detailed assessment of the nerve-innervation pattern is required for diagnosis and treatment. Especially, deep muscles are hard to examine and are as yet only accessible by uncomfortable and painful needle EMG techniques. Just recently, a new and flexible method and device became available to measure the small magnetic fields generated by the contraction of the muscles: optically pumped magnetometers (OPMs). OPMs are small devices that measure the zero-field level crossing resonance of spin-polarized rubidium atoms. The resonance is dependent on the local magnetic field strength, and therefore, these devices are able to measure small magnetic fields in the range of a few hundred femtoteslas. In this paper, we demonstrate as a proof of principle that OPMs can be used to measure the low magnetic fields generated by small hand muscles after electric stimulation of the ulnar or median nerve. We show that using this technique, we are able to record differential innervation pattern of small palmar hand muscles and are capable of distinguishing between areas innervated by the median or ulnar nerve. We expect that the new approach will have an important impact on the diagnosis of nerve entrapment syndromes, spinal cord lesions, and neuromuscular diseases.

Multicentric reticulohistiocytosis: a case report

BackgroundMulticentric reticulohistiocytosis is a rare form of non-langerhans cell histiocytosis presenting with skin changes and erosive arthritis. Infiltration of histiocytes and multinucleated giant cells are typical histological findings and confirm the diagnosis.Case presentationThis case report describes a newly diagnosed case of multicentric reticulohistiocytosis in a healthy 26-year-old female originally from the Philippines. Eruption of papules and nodules on the hands and pain in multiple joints were the main complaints at the initial presentation. Radiographical findings of erosions in the small hand and feet joints were impressive. Initial histological findings did not match the clinical image, although later the clinical diagnosis was supported by histological findings in additional biopsies.ConclusionsAlthough initial histological findings did not match the clinical image, additional biopsies were valuable to confirm the diagnosis.

Co-existence of two rare conditions: Oculo-palato-cerebral syndrome and congenital chylothorax

Background: Oculo-palato-cerebral syndrome is an extremely rare condition characterized by various features, including low-birth weight, microcephaly, cerebral atrophy, mild-to-severe developmental delay, cleft palate, persistent hyperplastic primary vitreous, microphthalmia, small hands and feet, joint laxity, and large ears with thick helices. Diagnosis of this syndrome is based on the clinical manifestations, particularly the presence of persistent hyperplastic primary vitreous in association with other malformations. Congenital chylothorax is also a rare condition in the neonatal period, which is caused by the abnormal accumulation of the lymphatic fluid within the pleural space. This condition may be detected prenatally or during the neonatal period. Case report: We presented the case of a patient with oculo-palato-cerebral syndrome and congenital chylothorax based on a literature review. Conclusion: Oculo-palato-cerebral syndrome and congenital chylothorax are both rare conditions. To the best of our knowledge, this was the first case report on congenital chylothorax in association with oculo-palato-cerebral syndrome in the available literature. Since there have only been five case reports on these patients, further evidence is required to confirm the possible association between these rare conditions.

Redundancy in the speech signal helps amusics perceive prosody

Speech is information dense, rapidly conveying segmental, semantic, syntactic, and prosodic information through the manipulation of a small handful of acoustic cues. As a result, impaired perception of one of these cues could impede acquisition of linguistic structure at multiple levels. For example, impaired perception of temporal patterns has been linked to developmental language delays. However, auditory impairments do not necessarily lead to language delays, suggesting that some people are able to compensate for difficulties with sound perception. This may be due to the perceptual redundancy of speech—the fact that multiple auditory dimensions often convey the same linguistic information. We tested this hypothesis by examining prosody perception in individuals with amusia, i.e., severe difficulties with the perception of musical melodies. First, we find that amusics show decreased functional connectivity between auditory and motor cortices during speech perception, suggesting that amusia is a domain-general deficit in pitch perception stemming from decreased auditory-motor connectivity. Second, we find that amusics compensate for their impairment by relying upon preserved perceptual abilities, suggesting that redundancy makes speech somewhat robust to individual differences in perceptual skill.

Correcting for bias in hot hand analysis: An application to youth golf

This paper illustrates the problems that arise with traditional tests for the hot hand and proposes instead using a consistent dynamic panel data estimator, which corrects for these problems and is easy to implement. The issue is demonstrated by performing regression analysis on a sample of simulated data for junior golfers that does not include any dependence in a golfer’s performance across holes. The traditional regression analysis finds evidence of both hot and cold hand effects, even though the data is known to have no such effects. We resolve this problem by applying the consistent dynamic panel data estimator to a large dataset of amateur, youth golfers, to find no evidence of either hot or cold hand effects overall. When we restrict attention to the most-amateur of the golfers in our data, we do see weak evidence of a small hot hand. Thus, casual athletes may experience small hot hands, but the effect does not persist among more serious athletes. This may give insight into why the belief in the hot hand in professional sports exists, even when the evidence suggests otherwise.

Survivin Measurement improves Clinical Prediction of Transition From Arthralgia to RA—Biomarkers to Improve Clinical Sensitivity of Transition From Arthralgia to RA

Background: Arthralgia often predates development of rheumatoid arthritis (RA). A set of joint symptoms commonly found in patients during their transition from arthralgia to RA, has been recently proposed.Aim: To combine clinical and serological markers and to improve recognition of imminent rheumatoid arthritis (RA) among patients with arthralgia.Methods: The total of 1,743 first-visit patients attending the rheumatology ward in Gothenburg for joint symptoms were identified during 12 consecutive months. Among those, 63 patients were classified as RA, 73 had undifferentiated arthritis and 180 had unexplained arthralgia. New RA cases, which prospectively developed during 48 months, comprised the preclinical (pre) RA group. The joint symptoms of the first-visit were analyzed aiming to distinguish patients with arthralgia and arthritis, and patients with pre-RA, who later developed the disease. The receiver operating characteristics curves were constructed. In the model, symptoms with the odds ratio >2.0 between the arthralgia and pre-RA were combined with information about RA-specific antibodies, C-reactive protein (CRP), and survivin in serum.Results: The proposed set of clinical symptoms distinguished the arthralgia patients from RA and pre-RA. Presence of survivin in serum showed strong association with clinical joint symptoms in arthralgia. A combination of symptoms in several small joint areas, increasing number of joints with symptoms, and patient's experience of swelling in small hand joints at the first visit identified pre-RA cases with 93% specificity. Grouping those symptoms with information about survivin, RA-specific antibodies, and CRP (or gender) in the final algorithm achieved 91% specificity and 55.2% of positive prediction for transition from arthralgia to RA.Conclusion: Clinical and serological parameters in combination aid recognition of imminent RA among arthralgia patients with appropriate sensitivity.

Simulation of electromyographic recordings following transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a technique that enables noninvasive manipulation of neural activity and holds promise in both clinical and basic research settings. The effect of TMS on the motor cortex is often measured by electromyography (EMG) recordings from a small hand muscle. However, the details of how TMS generates responses measured with EMG are not completely understood. We aim to develop a biophysically detailed computational model to study the potential mechanisms underlying the generation of EMG signals following TMS. Our model comprises a feed-forward network of cortical layer 2/3 cells, which drive morphologically detailed layer 5 corticomotoneuronal cells, which in turn project to a pool of motoneurons. EMG signals are modeled as the sum of motor unit action potentials. EMG recordings from the first dorsal interosseous muscle were performed in four subjects and compared with simulated EMG signals. Our model successfully reproduces several characteristics of the experimental data. The simulated EMG signals match experimental EMG recordings in shape and size, and change with stimulus intensity and contraction level as in experimental recordings. They exhibit cortical silent periods that are close to the biological values and reveal an interesting dependence on inhibitory synaptic transmission properties. Our model predicts several characteristics of the firing patterns of neurons along the entire pathway from cortical layer 2/3 cells down to spinal motoneurons and should be considered as a viable tool for explaining and analyzing EMG signals following TMS. NEW & NOTEWORTHY A biophysically detailed model of EMG signal generation following transcranial magnetic stimulation (TMS) is proposed. Simulated EMG signals match experimental EMG recordings in shape and amplitude. Motor-evoked potential and cortical silent period properties match experimental data. The model is a viable tool to analyze, explain, and predict EMG signals following TMS.

A Revelation of Purgatory

A Revelation of Purgatory

Challenging the Listener: How to Change Trends in Classical Music Programming

This article aims to provide the first large-scale description of current trends in classical music programming. The purpose is to analyze an issue commonly associated with the critical state of concert venues today, which is to say, the predominantly conservative aesthetic of performed repertoires. This paper attempts to go further than previous studies by looking at a larger group of repertoires and institutions, examining data from some 4,700 concerts performed between 2010 and 2015, randomly gathered by the database www.bachtrack.com. No other source in this field enjoys its sheer size and wide variety. The first section demonstrates that an extremely small handful of composers dominate the musical landscape, and that patterns of association between programmed composers within individual concerts are highly predictable. Against this problematic backdrop, the second section proposes possible remedies to balance this disproportionate concentration of specific styles, composers, and associations by focusing as a case study on the innovative music program at the Juan March Foundation in Madrid. The overall results are both original and valuable, as they reveal otherwise undetected trends in music programming, while providing practical strategies to re-engage audiences and encourage different cultural policies at concert halls.

Estimation of voluntary elicited motor neuron discharge using a peripheral nerve collision technique at different contraction strengths

ObjectiveTo estimate non-invasively the amount, recruitment pattern and discharge frequency of spinal motor neurons (MN) at contraction strength >20% of maximal voluntary contraction (MVC) of small hand muscles. MethodsA peripheral collision technique was used and consisted of supramaximal electrical stimuli at Erb's point and at the wrist, synchronizing descending volleys of action potential during voluntary isometric contractions of the abductor digiti minimi muscle at 20–80% of MVC strength and 1–8 s of contraction duration. Responses of 13 healthy volunteers were quantified and analysed using a recently described model of MN behaviour. ResultsA linear relationship between MN discharge and force generation was noticed with R2 = 0.996, and was confirmed using the simulation results (R2 = 0.997) for contraction durations up to 8 s. For each investigated force level, discharge frequency and recruitment pattern were calculated for individual MN. ConclusionsUsing this method, MN discharge properties during voluntary activity can be estimated non-invasively. SignificanceThis method provides new opportunities for the non-invasive study of MN behaviour, and could be expanded to patients with conduction failure and during fatigue.

Novel truncating PPM1D mutation in a patient with intellectual disability

Truncating mutations in the last and penultimate exons of the PPM1D gene were recently described as a cause for mild to severe intellectual disability in fourteen patients. Feeding difficulties, periods of fever and vomiting as well as a high pain threshold were described as additional characteristic features and the disorder was subsequently termed “intellectual developmental disorder with gastrointestinal difficulties and high pain threshold (IDDGIP)” in the OMIM database (MIM # 617450). Here we report on an additional patient carrying a novel de novo truncating mutation NM_003620.3: c.1535del, p.(Asn512Ilefs*2) in the last exon of PPM1D. While the patient showed features overlapping with the reported phenotype, such as a short stature and small hands and feet, he also presented with additional features like cleft lip and palate and an aberrant right subclavian artery. Notably, the patient did not have any gastrointestinal difficulties or periods of fever, indicating variability of the phenotype of patients with PPM1D mutations.

MEMBANGUN KINERJA PEMASARAN MELALUI MARKETING KNOWLEDGE COMPETENCE DAN MARKETING NETWORKING

This research is done based on research result differences ( research gap ) and differences of discussion focus about orientation of entrepreneurial and influence of knowledge interest and also company capability to marketing performance. Besides, there are also research problem about tightening of emulation in hand made clothes industry specially at small scale industry in Semarang city which’s owning local market so that push brooding company to be more ahead in formulating strategy to improving its performance. Some condition and factor above were importance to be checked empirically and analyzed. Therefore the practitioner / owner in hand made clothes industry can obtain fact to support their exist in market, so the formulated strategy earn more accurate. This research is done by taking research object at small scale hand made clothes industry in Semarang, amounting to 170 company with its population element that is manager / owner. Sampling technique that used is purposive sampling. Amount of determined responder as research sample is 100 people. Analysis technique that used to interpret and analyze data in this research is technique of Structural Equation Model (SEM) of software package of AMOS. Result of examination proven hypothesis that factor entrepreneurial orientation and knowledge of market become positive effect of marketing capability and marketing performance. It is mean high significance of each other variables. As for model which is raised in this research can be accepted posed at by index according to where value of GFI 0,900, value of chi-square 87,987, probability value 0,084, value of TLI 0,965 and value of CFI 0,973, all have up to standard although value of AGFI 0,853 accepted by marginal. Keywords : Entrepreneurial Orientation, Marketing Knowledge Competence, Marketing Capability, Marketing Networking, Performance

Split hand muscle echo intensity index as a reliable imaging marker for differential diagnosis of amyotrophic lateral sclerosis

ObjectiveThe objective of this study was to investigate the usefulness of muscle ultrasound in evaluating dissociated small hand muscle atrophy, termed ‘split hand’, and its feasibility in the diagnosis of...

TheJus ad Bellum’s Regulatory Form

AbstractThis article argues that a form of legal regulation is embodied in decisions at the UN Security Council that condone but do not formally authorize specific military operations. Such decisions sometimes inflect or go beyond what thejus ad bellumpermits through its general standards—that is, under the prohibition of cross-border force and small handful of exceptions. Recognizing that this form of regulation is both part of the law and different in kind from regulation through the general standards should change how we think about thejus ad bellum.

Molecular and clinical studies in 8 patients with Temple syndrome.

Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by phenotypic features including pre- and postnatal growth retardation, muscular hypotonia and feeding difficulties in infancy, early puberty and short stature with small hands and feet and often truncal obesity. It is caused by maternal uniparental disomies, paternal deletions and primary imprinting defects that affect the chromosomal region 14q32 and lead to a disturbed expression of imprinted genes in this region. Here, we present detailed clinical data of 8 patients with Temple syndrome, 4 with an imprinting defect, 2 with an imprinting defect in a mosaic state as well as 1 complete and 1 segmental maternal uniparental disomy of chromosome 14.

Repertoire Analysis of Antibody CDR-H3 Loops Suggests Affinity Maturation Does Not Typically Result in Rigidification.

Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the complementarity determining region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recent homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.

Assessing dengue transmission risk and a vector control intervention using entomological and immunological indices in Thailand: study protocol for a cluster-randomized controlled trial

BackgroundDengue fever is the most common and widespread mosquito-borne arboviral disease in the world. There is a compelling need for cost-effective approaches and practical tools that can reliably measure real-time dengue transmission dynamics that enable more accurate and useful predictions of incidence and outbreaks. Sensitive surveillance tools do not exist today, and only a small handful of new control strategies are available. Vector control remains at the forefront for combating dengue transmission. However, the effectiveness of many current vector control interventions is fraught with inherent weaknesses. No single vector control method is effective enough to control both vector populations and disease transmission. Evaluations of novel larval and adult control interventions are needed.Methods/designA cluster-randomized controlled trial will be carried out between 2017 and 2019 in urban community clusters in Khon Kaen and Roi Et cities, northeastern Thailand. The effectiveness of a pyriproxyfen/spinosad combination treatment of permanent water storage containers will be evaluated on epidemiological and entomological outcomes, including dengue incidence, number of female adult dengue vectors infected or not infected with dengue virus (DENV), human exposure to Aedes mosquito bites, and several other indices. These indices will also be used to develop predictive models for dengue transmission and impending outbreaks. Epidemiological and entomological data will be collected continuously for 2 years, with the intervention implemented after 1 year.DiscussionThe aims of the trial are to simultaneously evaluate the efficacy of an innovative dengue vector control intervention and developing predictive dengue models. Assessment of human exposure to mosquito bites by detecting antibodies generated against Aedes saliva proteins in human blood samples has, so far, not been applied in dengue epidemiological risk assessment and disease surveillance methodologies. Likewise, DENV detection in mosquitoes (adult and immature stages) has not been used in any practical way for routine disease surveillance strategies. The integration of multiple outcome measures will assist health authorities to better predict outbreaks for planning and applying focal and timely interventions. The trial outcomes will not only be important for Thailand, but also for the entire Southeast Asian region and further afield.Trial registrationISRCTN, ISRCTN73606171. Registered on 23 June 2017.

Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson syndrome

BackgroundRothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases. MethodsThree Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members. ResultsThe probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser. ConclusionOur study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.

Why the Realism Debate Matters for Science Policy: The Case of the Human Brain Project

There has been a great deal of skepticism towards the value of the realism/anti-realism debate. More specifically, many have argued that plausible formulations of realism and anti-realism do not differ substantially in any way (Fine 1986; Stein 1989; Blackburn 2002). In this paper, I argue against this trend by demonstrating how a hypothetical resolution of the debate, through deeper engagement with the historical record, has important implications for our criterion of theory pursuit and science policy. I do this by revisiting Arthur Fine’s ‘small handful’ argument for realism and show how the debate centers on whether continuity (either ontological or structural) should be an indicator for the future fruitfulness of a theory. I then demonstrate how these debates work in practice by considering the case of the Human Brain Project. I close by considering some potential practical considerations of formulating meta-inductions. By doing this, I contribute three insights to the current debate: 1) demonstrate how the realism/anti-realism debate is a substantive debate, 2) connect debates about realism/anti-realism to debates about theory choice and pursuit, and 3) show the practical significance of meta-inductions.