Search

Phosphorylated Tau proteins are promising biomarkers for the diagnosis and prognosis of Alzheimer's disease. This study presents a novel voltametric sensor using a vanadium MXene polydopamine (VxPDA) redox active composite and a Tau-441-specific polyaniline molecularly imprinted polymer (PANI MIP) for the sensitive detection of Tau-441 in interstitial fluid (ISF) and plasma. The VxPDA/PANI MIP sensor demonstrates a broad detection range of 5 fg/mL to 5 ng/mL (122 aM/L to 122 pM/L) in ISF without the use of redox mediators, with a lower limit of detection (LOD) of 2.3 fg/mL (60 aM/L). Furthermore, a handheld device utilizing this technology successfully detects Tau-441 in artificial serum with high sensitivity (5 fg/mL to 150 fg/mL (122 aM/L to 366 aM/L)) and specificity within a clinically relevant range. The rapid detection time (∼32 min) and low cost (∼£20/device) of this sensor highlight its potential for minimally invasive, early AD diagnosis in clinical settings. This advancement aims to facilitate a transition away from invasive cerebrospinal fluid (CSF)-based diagnostic techniques for AD.

Over the last decade, a significant paradigm shift has been observed towards leveraging less invasive biological fluids—such as skin interstitial fluid (ISF), sweat, tears, and saliva—for health monitoring. This evolution seeks to transcend traditional, invasive blood-based methods, offering a more accessible approach to health monitoring for non-specialized personnel. Skin ISF, with its profound resemblance to blood, emerges as a pivotal medium for the real-time, minimally invasive tracking of a broad spectrum of biomarkers, thus becoming an invaluable asset for correlating with blood-based data. Our exploration delves deeply into the development of wearable molecular biosensors, spotlighting dermal sensors for their pivotal roles across both clinical and everyday health monitoring scenarios and underscoring their contributions to the holistic One Health initiative. In bringing forward the myriad challenges that permeate this field, we also project future directions, notably the potential of skin ISF as a promising candidate for continuous health tracking.Moreover, this paper aims to catalyse further exploration and innovation by presenting a curated selection of seminal technological advancements. Amidst the saturated landscape of analytical literature on translational challenges, our approach distinctly seeks to highlight recent developments. In attracting a wider spectrum of research groups to this versatile domain, we endeavour to broaden the collective understanding of its trajectory and potential, mapping the evolution of wearable biosensor technology. This strategy not only illuminates the transformative impact of wearable biosensors in reshaping health diagnostics and personalized medicine but also fosters increased participation and progress within the field. Distinct from recent manuscripts in this domain, our review serves as a distillation of key concepts, elucidating pivotal papers that mark the latest advancements in wearable sensors. Through presenting a curated collection of landmark studies and offering our perspectives on the challenges and forward paths, this paper seeks to guide new entrants in the area. We delineate a division between wearable epidermal and subdermal sensors—focusing on the latter as the future frontier—thereby establishing a unique discourse within the ongoing narrative on wearable sensing technologies.

PURPOSETo identify the optimum strength of advanced modeled iterative reconstruction (ADMIRE) to achieve the best subjective and objective image quality when combining three-dose reduction strategies, ultra-high-pitch computed tomography coronary angiography (FLASH CTCA; with single-dose ivabradine to lower heart rate), low tube voltage, and ADMIRE.METHODSSixty consecutive patients underwent FLASH CTCA at 100 kVp in this single-center prospective study. Single-dose ivabradine was administered to patients whose heart rate was above 75 bpm. Images were reconstructed using the three highest strengths of ADMIRE (A3, A4, and A5). Objective and subjective image quality (using a Likert scale) were evaluated in the three datasets.RESULTSThe signal strength remained unchanged but mean noise significantly reduced across the increasing strengths of ADMIRE [signal: 513.78 ± 101.7 Hounsfield units (HU) at A3, 515.6 ± 100.5 HU at A4, and 519.7 ± 107.9 HU at A5; noise: 23.4 ± 4.5 HU at A3, 20.2 ± 3.6 HU at A4, and 17.2 ± 3.3 HU at A5]. Signal-to-noise and contrast-to-noise ratios were the highest at A5, and A5 offered significantly higher Likert scores in image noise, vessel sharpness, and overall image quality than A3 or A4. Additionally, A5 did not interfere with image interpretation in any patient.CONCLUSIONUsing all three dose reduction strategies during FLASH CTCA along with single-dose ivabradine administration ensures minimal radiation exposure in daily practice. In this study, A5 datasets had the best overall subjective and objective image quality despite their “plastic appearance”. In the future, enhanced dose reduction can be obtained by further lowering tube voltages.

Objective Nonspecific aorto-arteritis (NSAA) may involve the myocardium in the form of edema and fibrosis. We conducted this study to investigate role of cardiac MRI including late gadolinium enhancement (LGE), T1 and T2 mapping in the assessment of cardiac involvement in NSAA. Methods and Materials Over the period between 2016 and 2019, 36 patients with NSAA presenting with uncontrolled hypertension, left ventricular dysfunction, congestive cardiac failure, or tachyarrhythmia were included in the study. We also had 16 voluntary control patients for providing normal T1 and T2 mapping values. Results The average age of patients was 27.1 years and the majority were females. MRI is more sensitive than echocardiography in the detection of LV dysfunction and RWMA. Out of 36 patients, 10 (27.8%) had LGE. The most common pattern of midmyocardial enhancement was present in 5 out of 10 patients. Five (13.8%) patients show mid-myocardial enhancement, followed by epicardial enhancement, which was seen in four (11.11%) patients. The values of post-gad T1 mapping values were significantly lower than pre-gad T1 mapping values. At a cut-off global native T1 mapping value of 1019 milliseconds had the sensitivity of 83.3% and specificity of 81.2% in detecting an abnormal T1 map. No significant association of MRI contrast enhancement with elevated ESR and CRP levels. There was no significant relation of myocardial T2 mapping values between NSAA and control groups. Conclusion Quantitative tissue characterization in the myocardium with native T1 mapping values help in the detection of cardiac involvement in patients with NSAA. T1 mapping may provide incremental value in the assessment of myocardial involvement in NSAA in addition to LGE imaging.

Background Migration of the stent-graft post-thoracic endovascular aortic repair (TEVAR) is not uncommon; however, it is sparsely reported. The objective of this study was to assess the incidence, risk factors, and complications of stent-graft migration post-TEVAR. Materials and Methods Thirty-one patients who underwent TEVAR were retrospectively analyzed. The demographic, anatomical, and procedure-related factors were assessed. The measurements were done along the greater curvature of aorta around two fixed anatomic landmarks, that is, left common carotid artery or neoinnominate artery (hybrid repair) proximally and celiac artery distally. Aortic elongation and migration at proximal, distal, as well as at overlapping zone were measured. More than 10 mm of migration was considered significant. Results Significant migration was observed in six (19%) patients. No significant migration was observed in the overlapping zone. The proximal landing zone 3 (odds ratio [OR] 12.78, p 0.01) was a significant risk factor, whereas landing zone 2 was a protective factor against the migration (OR 0.08, p 0.02). The odds for migration were more in segments I/3 and II/3 compared with I/2 and II/2, respectively, as per Modified Arch Landing Areas Nomenclature. A single complication was seen in the migration group which was treated by an overlapping stent graft. Conclusion The stent-graft migration after TEVAR is not uncommon. Type 3 proximal landing zone was a significant risk factor for migration with an increased risk toward I/3 and II/3. Proximal landing zone 2 as well as adequate overlapping distance in multiple stent grafts can prevent migration. Ethical Approval No IECPG-227/24.06.2020

Transdermal drug delivery systems offer several advantages over conventional oral or hypodermic administration due to the avoidance of first-pass drug metabolism and gastrointestinal degradation as well as patients’ convenience due to a minimally invasive and painless approach. A novel transdermal drug delivery system, comprising a combination of transfersomes with either solid silicon or solid polycarbonate microneedles has been developed for the transdermal delivery of aspirin. Aspirin was encapsulated inside transfersomes using a “thin-film hydration sonication” technique, yielding an encapsulation efficiency of approximately 67.5%. The fabricated transfersomes have been optimised and fully characterised in terms of average size distribution and uniformity, surface charge and stability (shelf-life). Transdermal delivery, enhanced by microneedle penetration, allows the superior permeation of transfersomes into perforated porcine skin and has been extensively characterised using optical coherence tomography (OCT) and transmission electron microscopy (TEM). In vitro permeation studies revealed that transfersomes enhanced the permeability of aspirin by more than four times in comparison to the delivery of unencapsulated “free” aspirin. The microneedle-assisted delivery of transfersomes encapsulating aspirin yielded 13-fold and 10-fold increases in permeation using silicon and polycarbonate microneedles, respectively, in comparison with delivery using only transfersomes. The cytotoxicity of different dose regimens of transfersomes encapsulating aspirin showed that encapsulated aspirin became cytotoxic at concentrations of ≥100 μg/mL. The results presented demonstrate that the transfersomes could resolve the solubility issues of low-water-soluble drugs and enable their slow and controlled release. Microneedles enhance the delivery of transfersomes into deeper skin layers, providing a very effective system for the systemic delivery of drugs. This combined drug delivery system can potentially be utilised for numerous drug treatments.

Background: The introduction of Sirolimus Eluting Coronary Stents (SES) was a major breakthrough in interventional cardiology. The large, randomized, clinical trials using SES have shown a remarkable reduction in angiographic restenosis and target vessel revascularization (TVR) compared with bare-metal stents as well as other drug-eluting stents (DESs). However, there is only limited data on the outcome of Indian patients treated by DES of Indian origin. The purpose of the study was to evaluate the outcomes of the supraflex sirolimus-eluting coronary stents for the treatment of coronary artery disease and to determine major adverse cardiovascular and cerebrovascular events (MACCE). Materials and Methods: This was a single-centre, observational, nonrandomized study that enrolled unselected real-world patients at a tertiary care center who had undergone implantation with supraflex sirolimus-eluting stents. The primary end-point of the study was MACCE, which is a conglomeration of cardiac death, target lesion revascularization (TLR), TVR, cerebrovascular accident (CVA), and heart failure at 1-year follow-up. Results: A total of 100 patients were intervened successfully with sirolimus-eluting stents. Out of total patients, diabetes and hypertension were observed in 38% and 35% of patients. According to ACC/AHA classification, there were 68% Type B lesions and 32% Type C lesions. At 1-year follow-up, MACE was found to be 11%, which is a composite of 4% TLR, 3% TVR, 1% CVA, and 5% heart failure. Diabetes (P = 0.02), hypertension (P = 0.01), kidney dysfunction (P = 0.002), and LV function (P = 0.01) strongly correlate with outcome (MACCE). Conclusion: There was an acceptable rate of adverse events after implantation of the supraflex sirolimus-eluting stents, although it was slightly higher compared to other studies. Diabetes, hypertension, kidney dysfunction, and LV function strongly correlate with outcome (MACCE).

Abstract This work presents a machine learning based method for bi-fidelity modelling. The method, a Knowledge Based Neural Network (KBaNN), performs a local, additive correction to the outputs of a coarse computational model and can be used to emulate either experimental data or the output of a more accurate, but expensive, computational model. An advantage of the method is that it can scale easily with the number of input and output features. This allows bi-fidelity modelling approaches to be applied to a wide variety of problems, for instance in the bi-fidelity modelling of fields. We demonstrate this aspect in this work through an application to Computational Fluid Dynamics, in which local corrections to a velocity field are performed by the KBaNN to account for mesh effects. KBaNNs were trained to make corrections to the free-stream velocity field and the boundary layer. They were trained on a limited data-set consisting of simple two-dimensional flows. The KBaNNs were then tested on a flow over a more complex geometry, a NACA 2412 airfoil. It was demonstrated that the KBaNNs were still able to provide a local correction to the velocity field which improved its accuracy. The ability of the KBaNNs to generalise to flows around new geometries that share similar physics is encouraging. Through knowledge based neural networks it may be possible to develop a system for bi-fidelity, computer based design which uses data from past simulations to inform its predictions.

Background Congenital coronary artery anomalies (CCAA) are predominantly discovered as incidental findings on computed tomography coronary angiography (CTCA) of adults. They are rare but significant, considering their importance during endovascular or surgical interventions. This study describes the prevalence of CCAA and coronary variants (CV) in adults as identified by CTCA. Methods It is a retrospective evaluation of 7,694 CTCAs of adults performed in a tertiary care facility in North India. Results CCAA and CV were observed in a total of 9.6% of patients. The most common CV was myocardial bridging, observed in 7.1%. Anomalies of origin and course were detected in 2.3% of the patients. The frequency of these anomalies in the right coronary artery, left main, left circumflex artery, and the left anterior descending artery arteries were 1.06, 0.41, 0.03, and 0.38%, respectively. The single coronary pattern was seen in 0.05% and coronary artery fistulas in 0.03%. Scrutiny of data on Indian regional distribution revealed differing definitions and inclusion and exclusion criteria, making comparisons difficult, highlighting the need for uniform definitions as well as the need to adopt a standardized reporting template and format. Conclusion The prevalence of CCAA and CV is 9.6% in adult Indian patients undergoing CTCA. Prior knowledge of these anatomical finding can prevent a catastrophe during surgery or endovascular interventions. Hence, it is important that clinicians, as well as radiologists, are aware of these entities.

Introduction: Prostate cancer ranks second among all cancers affecting men. Common diagnostic tests like Transrectal Ultrasound (TRUS) and Prostate-Specific Antigen (PSA) are suboptimal for diagnostic purpose. Magnetic Resonance Imaging (MRI) has a promising role in detection, guidance for targeted biopsy and staging of prostate cancer. Aim: To evaluate the role of TRUS and MRI in the detection of prostate cancer and to ascertain if any functional parameter or union of parameters is of any utility in detection of prostate cancer. Materials and Methods: A prospective study was conducted which included fifty patients who underwent TRUS and 1.5-T MRI before being subjected toTRUS-guided biopsy. Imaging was compared with histopathological results. The sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio for each of the investigation was calculated. Results: The accuracy of the model combining all the imaging variables {T2-weighted imaging (T2WI), MR spectroscopy (MRS), Diffusion-Weighted Imaging (DWI), Apparent Diffusion Coefficient (ADC) and Dynamic Contrast-Enhanced (DCE) MRI} in predicting prostate cancer was 94%, which was higher than the diagnostic accuracy of each variable considered alone (DWI, 92%; ADC, 92%; MRS, 88.0%; DCE-MRI, 92%; and T2WI, 72%). TRUS had a diagnostic accuracy of 80%, sensitivity of 100.0%, specificity of 67.7%, PPV of 65.5% and NPV of 100.0%. Conclusion: TRUS had a high sensitivity and negative predictive value but a low specificity. MRI had both high sensitivity and specificity especially when the combination of functional sequences was used. But, the addition of a third functional technique does not further improve detection. Thus, a limited number of functional sequences are needed in every MRI study for prostatic cancer. However, DWI being the most valuable should be included as one of the sequences.

Objective: To establish the incidence of arterial corona mortis variant in angiographic studies being performed using a 64 slice CT scan machine in a series of patients.Methods: This was a prospective cross-sectional study including 100 consecutive patients undergoing routineclinically indicated, standard protocol, CT-angiography for the abdominal aorta and/or lower limbs using a 64 slice CT scanner. Patients having severe arterial insufficiency (Grade 4 stenosis on CT angiography), pelvic infections and tumours, patients with past pelvic trauma and those who had previous pelvic surgery were excluded from the study. In total 200 hemi-pelvises were evaluated for the presence or absence of corona morti.Results: Overall, we included 100 patients in this series including 67 men and 33 women with mean age of 40.1±2.3 (ranging from 22-74) years. The arterial variant was identified on thin, 0.625-mm-thick images in 24 out of 100 patients studied (unilateral in 20 patients and bilateral in 4 patients; 28 out of 200 hemipelvises evaluated, having an incidence of 14%). We found that the distance of corona mortis artery from the symphysis was significantly greater for women compared to men, both on right (p=0.034) and left sides (p=0.046).Conclusion: Corona mortis may be prospectively identified at contrast-enhanced multidetector CT especially in pelvic trauma patients and help guide subsequent endovascular embolization or surgical interventions.

Background: Pulmonary stenosis in patients with common arterial trunk protects the pulmonary vasculature. In our recently published prospective study of common arterial trunk, some patients with sinusal origin of the pulmonary arterial segment had pulmonary stenosis induced by systolic excursion of a truncal valvar leaflet. We aimed to determine the detailed morphologic characteristics of this unusual finding. Methods and Results: All 70 patients underwent echocardiography and computed tomographic angiography as per predefined study protocol. In selected cases, we also performed cardiac catheterization. Among 27 patients with aortic dominance, we found sinusal origin of the pulmonary arterial segment. In 5 of these patients, pulmonary stenosis was induced by systolic excursion of a truncal valvar leaflet. In all these patients, the truncal valve was trisinusate, albeit with asymmetric sinuses. The pulmonary arterial segment arose from the largest left sinus with its relatively large leaflet obstructing the pulmonary orifice during systole. In the remaining 22 patients, without pulmonary stenosis but with sinusal origin of pulmonary arterial segment, the truncal valve was quadrisinusate in 7, bisinusate in 2, and trisinusate in 13. None of the patients with quadrisinusate and bisinusate truncal valves had pulmonary stenosis. Among the 13 patients with trisinusate valves, the sinuses of the truncal valve were symmetrical in 6, while in 7, the pulmonary orifice originated from a smaller asymmetric sinus. Conclusion: Pulmonary stenosis, produced by a relatively large leaflet of an asymmetric truncal sinus, may prevent early development of pulmonary vascular disease. Timely recognition of this unusual mechanism of pulmonary stenosis is important for optimal management.

L-2 Hydroxyglutaric aciduria is a rare metabolic disorder which is autosomal recessive in inheritance. It is characterised by the increased urinary excretion of L-2 hydroxyglutaric acid and the diagnosis is based on the increased levels of the L-2 hydroxy glutaric acid in the urine, serum & CSF. This is a neurometabolic disorder which is associated with slowly progressive psychomotor delay since childhood. We report a case of an 18 –year old female who presented at the emergency department with seizures, fever and on imaging show classic features.

Technological substitutions play a major role in the research and development efforts of most modern industries. If timed and provisioned well, successful technology substitutions can provide significant market advantages to firms that have anticipated the demand correctly for emergent technologies. Conversely, failure to commit to new technologies at the right time can have catastrophic consequences, making determining the likely substitution mode of critical strategic importance. With little available data, being able to identify at an early stage whether new technologies are appearing in response to the perceived stagnation in existing technical developments, or as a result of pioneering leaps of scientific foresight, poses a significant challenge. This paper combines bibliometric, pattern recognition, and statistical approaches to develop a technology classification model from historical datasets where literature evidence supports mode labeling. The resulting functional linear regression model demonstrates robust predictive capabilities for the technologies considered, supporting the literature-based substitution framework applied and providing evidence suggesting that substitution modes can be recognized through automated processing of patent data. Furthermore, preliminary evidence suggests that classification can be achieved based on partial time series, implying that future extensions to real-time classifications may be possible for decision-making in the early stages of research and development.

In patients with thalassemia major (TM), cardiac magnetic resonance feature-tracking (CMR-FT) has been shown to be an effective method for diagnosing subclinical left ventricular (LV) dysfunction. This study aimed to determine whether CMR-FT could detect abnormal RV dysfunction in patients with a normal right ventricular ejection fraction (RVEF). We performed a retrospective analysis of TM patients admitted to Dubai’s Rashid Hospital between July 2019 and March 2021. The inclusion criteria were TM patients with SSFP cine with T2* (T2*-weighted imaging), while exclusion criteria included any other cardiovascular disease. When there was no myocardial iron overload (MIO) (T2* ≥ 20 ms) and when there was significant MIO (T2* < 20 ms), the CMR-FT was used to correlate with EF. Among the 89 participants, there were 46 men (51.7%) and 43 women (48.3%), with a mean age of 26.14 ± 7.4 years (range from 10 to 48 years). Forty-six patients (51.69%) did not have MIO, while 43 individuals did (48.31%). Thirty-nine patients (32.6%) were diagnosed with severe MIO, while seventeen (19.1%) were diagnosed with mild to moderate MIO. A significant correlation existed between RVEF and T2* values (r = 0.274, p = 0.014) and between left ventricular ejection fraction (LVEF) and T2* values (r = 0.256, p = 0.022). Using a multiple logistic regression model with predictors such as right ventricular longitudinal strain (RVGLS), LV ejection fraction (LV EF), and hemoglobin, abnormal myocardial iron overload can be predicted. This model demonstrates an AUC of 78.3%, a sensitivity of 72%, and a specificity of 76%. In the group with preserved RVEF > 53%, the left ventricular radial strain (LVGRS) (p = 0.001), right ventricular radial strain (RVGRS) (p = 0.000), and right ventricular basal circumferential strain (RVGCS-basal) (p = 0.000) CMR-FT strain values are significantly lower than those of the control group (p > 0.05). There was no significant correlation between the LVGLS and T2*. RVGLS was ranked among the most accurate predictors of abnormal myocardial iron overload. The LVGRS, RVGRS, and RVGCS-basal CMR-FT strain values were the best predictors of subclinical RV dysfunction in the group with preserved RVEF. The most accurate way to diagnose MIO is still T2*, but FT-strain can help us figure out how MIO affects the myocardium from a pathophysiological point of view.

Cerebral small vessel disease (cSVD) has a crucial role in lacunar stroke and brain hemorrhages and is a leading cause of cognitive decline and functional loss in elderly patients. Based on underlying pathophysiology, cSVD can be subdivided into amyloidal and non-amyloidal subtypes. Genetic factors of cSVD play a pivotal role in terms of unraveling molecular mechanism. An important pathophysiological mechanism of cSVD is blood-brain barrier leakage and endothelium dysfunction which gives a clue in identification of the disease through circulating biological markers. Detection of cSVD is routinely carried out by key neuroimaging markers including white matter hyperintensities, lacunes, small subcortical infarcts, perivascular spaces, cerebral microbleeds, and brain atrophy. Application of neural networking, machine learning and deep learning in image processing have increased significantly for correct severity of cSVD. A linkage between cSVD and other neurological disorder, such as Alzheimer’s and Parkinson’s disease and non-cerebral disease, has also been investigated recently. This review draws a broad picture of cSVD, aiming to inculcate new insights into its pathogenesis and biomarkers. It also focuses on the role of deep machine strategies and other dimensions of cSVD by linking it with several cerebral and non-cerebral diseases as well as recent advances in the field to achieve sensitive detection, effective prevention and disease management.

Introduction: To determine whether Computed Tomography Perfusion (CTP) can predict treatment response and prognosis in non-small cell lung cancers (NSCLC). To determine which one of the perfusion parameter correlated best with treatment outcome. Methods: Sixteen patients with NSCLC underwent CTP before and after completion of chemo-radiotherapy. Patients with complete and partial response were grouped as responders and patients with stable and progressive disease were grouped as non-responders. Pre and post-treatment whole tumour perfusion parameters (blood flow - BF, blood volume - BV, mean transit time - MTT and permeability surface area product - PS) were compared between responders and non-responders. Results: Responders had higher baseline BF and PS values than non-responders; P = 0.047, 0.028 respectively. On 1 year follow up, patients with even 2.65% increase in PS value from baseline developed metastasis while patients with decrease in PS value by 24% did not develop metastasis (P = 0.05). Greater decrease in BF values (17%) were noted among responders than non-responders (2.4%) following chemoradiation, though the results were not statistically significant (P > 0.05). Conclusions: Tumours with higher baseline BF and PS respond well to chemo-radiation. Changes in the PS values can predict the development of metastasis and hence, the long term outcome.

Persistence of the embryological fifth aortic arch in postnatal life has been a subject of debate for over more than a century. We describe a patient with congenital kyphoscoliosis and variant anatomy in the aortic arch and brachiocephalic trunk which could be possibly explained by the persistence of bilateral fifth aortic arches, a pattern which has never been previously reported in literature.

Graphene-based point-of-care (PoC) and chemical sensors can be fabricated using photolithographic processes at wafer-scale. However, these approaches are known to leave polymer residues on the graphene surface, which are difficult to remove completely. In addition, graphene growth and transfer processes can introduce defects into the graphene layer. Both defects and resist contamination can affect the homogeneity of graphene-based PoC sensors, leading to inconsistent device performance and unreliable sensing. Sensor reliability is also affected by the harsh chemical environments used for chemical functionalisation of graphene PoC sensors, which can degrade parts of the sensor device. Therefore, a reliable, wafer-scale method of passivation, which isolates the graphene from the rest of the device, protecting the less robust device features from any aggressive chemicals, must be devised. This work covers the application of molecular vapour deposition technology to create a dielectric passivation film that protects graphene-based biosensing devices from harsh chemicals. We utilise a previously reported “healing effect” of Al2O3 on graphene to reduce photoresist residue from the graphene surface and reduce the prevalence of graphene defects to improve graphene device homogeneity. The improvement in device consistency allows for more reliable, homogeneous graphene devices, that can be fabricated at wafer-scale for sensing and biosensing applications.

Aortic dissection is a medical emergency that can quickly lead to death, despite optimal treatment. The Stanford classification is widely used and is in close relationship to clinical practice, as type A dissections require primary surgical repair whereas type B dissections are treated medically as initial treatment with surgery or endovascular repair (EVR) reserved for any complications. Multislice CT is the investigation of choice to establish the diagnosis and plan treatment strategies. Therapeutic strategies differ for treatment of an acute dissection compared with a chronic dissection. Traditionally, most institutions favor a “complication specific” approach for type B dissection with antihypertensive treatment and use of β-blockers as primary therapy. Surgery or EVR is reserved for patients with recurrent pain, life-threatening complications, or rapid aortic expansion. With above algorithms, there is evidence that 30 to 50% patients on conservative therapy develop serious morbidity or mortality over 5-year period. Clinical and imaging markers of adverse outcome are being identified to revise the management strategies and offer EVR to those at risk for adverse outcome. This is especially relevant in view of the fact that EVR for type B dissection is associated with procedural success in 99.2 ± 0.1% patients. Overall survival rates of 96.9% at 30 days, 96.7% at 6 months, 96.4% at 1 year, 95.6% at 2 years, and 95.2% at 5 years are reported after EVR in type B dissections. There is emerging evidence that EVR may be noninferior to surgery in this group of patients. These observations along with the development of dissection-specific device designs have the potential to rewrite the management algorithms for type B aortic dissection and define the role of EVR in this disease.

The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective.We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases. Keywords: Microneedles, Minimally invasive sensors, Continuous glucose monitoring (CGM), Continuous lactate monitoring (CLM), Interstitial therapeutic drug monitoring (iTDM)

Chest-drain insertion is considered to be a benign procedure. A 6-year-old girl who is a known case of hyper-IgE/Job's syndrome presented to us following three episodes of fresh bleed following chest-drain insertion for the left lung abscess. The site of bleed was localized to be the ruptured pseudoaneurysm of the anterior segmental branch of the left pulmonary artery. For successful management, various pitfalls and gray areas have been highlighted: (a) the procedure of chest-drain insertion has a potential for many complications some of which may be life-threatening, (b) the importance of proper history taking and a complete evaluation of all patients before surgical intervention, (c) role of ultrasound-guided chest-drain insertion, and (d) the importance of lateral and pragmatic approach with multidisciplinary involvement in such unusual and challenging cases cannot be overemphasized.

Summary: Background: Enhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers. Methods: This first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK). The study was approved by London-Harrow Regional Ethics Committee. Volunteers were identified through emails sent to a healthy volunteer database from the Imperial College Clinical Research Facility. Volunteers, who had to be older than 18 years, were excluded if they had evidence of active infection, allergies to penicillin, were at high risk of skin infection, or presented with anaemia during screening. Participants wore a solid microneedle β-lactam biosensor for up to 6 h while being dosed at steady state with oral phenoxymethylpenicillin (five 500 mg doses every 6 h). On arrival at the study centre, two microneedle sensors were applied to the participant's forearm. Blood samples (via cannula, at −30, 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) and extracellular fluid (ECF; via microdialysis, every 15 min) pharmacokinetic (PK) samples were taken during one dosing interval. Phenoxymethylpenicillin concentration data obtained from the microneedles were calibrated using locally estimated scatter plot smoothing and compared with free-blood and microdialysis (gold standard) data. Phenoxymethylpenicillin PK for each method was evaluated using non-compartmental analysis. Area under the concentration–time curve (AUC), maximum concentration, and time to maximum concentration were compared. Bias and limits of agreement were investigated with Bland–Altman plots. Microneedle biosensor limits of detection were estimated. The study was registered with ClinicalTrials.gov, number NCT03847610. Findings: Ten healthy volunteers participated in the study. Mean age was 42 years (SD 14). Seven (70%) were men. Microdialysis and microneedle results were similar for phenoxymethylpenicillin ECF maximum concentration (0·74 mg/L vs 0·64 mg/L; 95% CI −0·24 to 0·44; p=0·53), time to maximum concentration (1·18 h vs 1·10 h; −0·52 to 0·67; p=0·79), and AUC (1·54 mg × h/L vs 1·67 mg × h/L; −1·10 to 0·85; p=0·79). In total, 440 time points were compared with mean difference between measurements −0·16 mg/L (95% CI −1·30 to 0·82). Mean phenoxymethylpenicillin AUCs for free serum and microneedle PK were similar (1·77 mg × h/L [SD 0·59] vs 1·67 mg × h/L [1·00]; −0·77 to 0·97; p=0·81). Median coefficient of variation between sensors within individuals was 7% (IQR 4–17). Limit of detection for the microneedles was estimated at 0·17 mg/L. Interpretation: This study is proof-of-concept of real-time, microneedle sensing of penicillin in vivo. Future work will explore microneedle use in patient populations, their role in data generation to inform dosing recommendations, and their incorporation into closed-loop control systems for automated drug delivery. Funding: National Institute for Health Research Imperial Biomedical Research Centre, Mérieux Foundation.

During the early stages of any system design, a thorough exploration of the design space can prove to be challenging and computationally expensive. The challenges are further exacerbated when dealing with complex systems, such as an aircraft, due to the high dimensionality of their design space. Arising from the Toyota Product Development System, set-based design allows parallel evaluation of multiple alternative configurations in the early design stages. At the same time, optimisation methods can be employed at later stages to fine-tune the engineering characteristics of design variants. Presented in this paper, is the Augmented set-based Design and OPTimisation (ADOPT) Framework that introduces a novel methodology for integrating the two areas. This allows for a thorough design-space exploration while ensuring the optimality of the selected designs. The framework has been developed using a process-independent and tool-agnostic approach so that it can be applied to the design process of varying kinds of systems. To demonstrate the implementation and potential benefits, the framework has been applied to the design of a generic aircraft fuel system. The results from the case study and the framework itself are discussed, with a number of areas for further development and future work being identified and presented.

Tuberculosis (TB) is a major public health problem worldwide. It can virtually affect any tissue in the body. Musculo-skeletal forms constitute only 1-3% of all tuberculous infections. Spine is the most common site, followed by peripheral joints. Tuberculosis is a double-edged sword in clinical practice. Making an incorrect diagnosis of tuberculosis is potentially as harmful as missing the diagnosis in true cases. A false positive diagnosis of tuberculosis not only results in ineffective treatment but also administration of antitubercular drugs in these patients can result in toxic side effects. A variety of clinical conditions mimic tuberculosis in bones and joints. Absence of pathognomonic imaging findings in extra-axial osetoarticular TB makes it even more difficult to make an accurate diagnosis radiologically in these patients. Pyogenic and fungal infections, inflammatory arthritis like rheumatoid arthritis are the common mimickers. Differential diagnosis varies according to the site affected, like bone tumours like enchondroma and giant cell tumour may mimic tubercular dactylitis. Clinical and radiological features of the extraspinal osteoarticular TB have been summarized in this review with illustrations. Radiological features and practical points of difference of the clinically relevant mimickers of the musculo-skeletal TB have been summed up.

Background and purpose: World Health Organization estimated that there were 600,000 new cases of head and neck cancers and 300,000 deaths each year worldwide. Scientific modalities to predict the treatment outcomes are not available yet. We conducted this study to (1) compare CT perfusion parameters before and after chemoradiation among patients with head and neck squamous cell carcinoma and (2) to evaluate the prognostic value of each perfusion parameter in predicting the response to chemoradiation. Materials and methods: We conducted a prospective study among all patients with head and neck squamous cell carcinoma registered for chemoradiotherapy (CRT) at Regional Cancer Research Center, Shimla, Himachal Pradesh, India during the period June 2012 through June 2013. CTp data were acquired on a 64-slice CT scanner (Light speed VCT Xte; GE Healthcare) with 14 cm z-axis coverage using Volume Helical Shuttle (VHS) feature at baseline, on completion of 40 Gy and 66 Gy of chemoradiation. We dichotomised the treatment outcome as complete response and non-response (partial responders/stable disease/progressive disease) using RECIST 1.1 criteria. We compared all perfusion parameters at baseline, 40 Gy and 66 Gy of CRT between responders and non-responders. We dichotomised the perfusion parameters as high (>median value) and low (≤median value) to analyze association between perfusion parameters and treatment outcome. We calculated the sensitivity, specificity, predictive values, and likelihood ratios for each dichotomized perfusion parameter using Wilson Score method. Results: We followed 24 patients (23 of them men) from start of the treatment till completion of it. All had Stage III or Stage IV of the disease. Blood flow (BF) and blood volume (BV) decreased and Mean Transit Time (MTT) increased significantly (p 106 ml/100 g/min) at baseline were five times more likely (p = 0.004) to respond to treatment as compared to those with low BF. BF was found to be 83.3% predictive of complete response. Other perfusion parameters were not significantly predictive of outcome (p > 0.05) Combination of high BF (>106 ml/100 g/min) and low (≤47 ml/100 g/min) permeability surface (PS) was 100% predictive of response to CRT irrespective of the stage of tumor. Conclusions: High BF at baseline is the single best predictor of response to chemoradiaton. A combination of high BF and low PS was found to be 100% predictive of complete response irrespective of the stage of the tumor.

Cardiovascular disease is a leading cause of mortality in renal transplant recipients. Coronary artery calcification (CAC) has been found to have good correlation with atherosclerosis and cardiovascular morbidity. The objective of our study was to assess the prevalence of CAC and the long-term effects of renal transplantation on CAC and carotid intima-medial thickness (CIMT) in Indian renal transplant recipients. Twenty-eight renal transplant recipients were included in this prospective study. Dual-source computed tomography and calcium scoring using Agatston′s method and CIMT measurement were performed at the time of transplant and then repeated at six and 12 months after transplantation. The prevalence of CAC in our study patients was low (32%), probably because they were young, had been on dialysis for a short duration and had undergone live-related renal transplant. An overall improvement in biochemical parameters was observed after transplantation. Patients with zero baseline calcium score did not show progression. Patients with baseline calcium score more than zero showed initial progression at 6 months and no further progression afterwards. There was good correlation between CIMT and CAC score. Our study suggests that renal transplantation does not reverse the calcification but appears to decrease the rate of progression in the long term.

Time series data available in huge amounts can be used in decision-making. Such time series data can be converted into information to be used for forecasting. Various techniques are available for prediction and forecasting on the basis of time series data. Presently, the use of data mining techniques for this purpose is increasing day by day. In the present study, a comprehensive survey of data mining approaches and statistical techniques for rainfall prediction on time series data was conducted. A detailed comparison of different relevant techniques was also conducted and some plausible solutions are suggested for efficient time series data mining techniques for future algorithms.

Background: Amplatzer vascular plugs (AVPs) are devices ideally suited to close medium-to-large vascular communications. There is limited published literature regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs). Aims: To describe the use of AVPs in different CCVMs and to evaluate their safety and efficacy. Materials and Methods: All patients who required an AVP for the closure of CCVM were included in this retrospective review of our catheterization laboratory data. The efficacy and safety of AVPs are reported. Results: A total of 39 AVPs were implanted in 31 patients. Thirteen (33%) were AVP type I and 23 (59%) were AVP type II. AVP type III were implanted in two patients and type IV in one patient. The major indications for their use included closure of pulmonary arteriovenous malformation (AVM) (n = 7), aortopulmonary collaterals (n = 7), closure of a patent Blalock-Taussig shunt (n = 5), systemic AVM (n = 5), coronary AVM (n = 4), patent ductus arteriosus (PDA) (n = 3), pulmonary artery aneurysms (n = 3), and venovenous collaterals (n = 2). Deployment of the AVP was done predominantly via the 5 - 7F Judkin′s right coronary guide catheter. Overall 92% of the AVPs could be successfully deployed and resulted in occlusion of the target vessel in all cases, within 10 minutes. No procedure-related or access site complication occurred. Conclusions: AVPs are versatile, easy to use, and effective devices to occlude the vascular communications in a variety of settings. AVP II is especially useful in the closure of tubular structures with a high flow.

Hemichorea hemiballismus is a rare manifestation seen in diabetic patients. MRI in these patients shows characteristic findings with T1w hyperintensity in striatum. We present a case of 60 year old female showing classical clinical and MRI features.

Post shunt meningeal fibrosis is an uncommon complication following VP shunt insertion and it presents with a diagnostic dilemma. It is a rare post shunt entity that may mimic chronic subdural hematoma on unenhanced CT and MR. Thus it is important to recognize it before any therapeutic intervention is being considered. We present a case of 47 year male who underwent VP shunt insertion for tubercular hydrocephalus 4 years ago. He presented with chronic headache for 6 months for which MRI brain was done. MRI finding revealed post shunt meningeal fibrosis thus differentiating from chronic subdural hematoma and hence obviated surgical drainage.

Portal vein aneurysm is an uncommon anomaly. Both congenital and acquired cases are reported. We report a case of idiopathic probably congenital portal vein aneurysm incidentally detected on contrast CT. There was no e/o any chronic liver disease or portal hypertension in this patient.

Diffusion tractography is a new imaging technique to display the traumatic region for valuable preoperative information with prognostic significance. We present a case of 54 year male with quadriparesis showing reduced FA values and increased ADC in injured segment with depiction of disrupted tracts on tractography.In the near future, DTI will become a part of routine imaging in trauma patients as experience with this novel method gains acceptance.

Unusual site metastasis as presenting complaint of renal cell carcinoma (RCC) has been reported previously in literature. RCC is a notorious tumor with unpredictable behavior. We present a case of RCC who presented with scrotal mass and on subsequent investigation was found to have metastasis to scrotum and spermatic cord. Both testes were normal with no evidence of metastasis.

Secondary pneumothorax is a very common medical emergency. At times it is associated with pneumomediastinum, which could be fatal at times if not identified. We present a case of a 11 years old sputum positive child who presented with both these conditions and was diagnosed on chest x ray.