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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that can cause cartilage and bone damage as well as a disability. Various cytokines play an essential role in disease formation such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-17, and macrophages; osteoclast is also activated by the cytokines, which cause bone degradation. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterized risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and using conventional, biological, and new non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favorable, many still do not respond to current therapies. The biologics have changed the disease progression over the past few decades, such as TNF-alpha inhibitors (infliximab, etanercept, adalimumab, golimumab, certolizumab), IL-1 inhibitors (anakinra), IL-6 inhibitors (tocilizumab), CD20 inhibitors (rituximab), and cytotoxic T-lymphocyte associated antigen (CTLA)-4 inhibitors (abatacept). In treatment with biologics, only little is known if "biologic-free" remission is possible in patients with sustained remission following intensive biological therapy. Infliximab and etanercept, in the long run, develop the drug antibody. This article has reviewed the action of the cytokine on joints and biological drug's action in blocking the cytokine degradation effect, benefits of biologics, and adverse effects in the long and short term. They are also effective alone or in combination with other drugs.

Rapid warm-up of a diesel engine aftertreatment system (ATS) is a challenge at low loads. Modulating exhaust manifold pressure (EMP) to increase engine pumping work, fuel consumption, and as a result, engine-outlet temperature, is a commonly used technique for ATS thermal management at low loads. This paper introduces exhaust valve profile modulation as a technique to increase engine-outlet temperature for ATS thermal management, without requiring modulation of exhaust manifold pressure. Experimental steady state results at 800 RPM/1.3 bar BMEP (curb idle) demonstrate that early exhaust valve opening with negative valve overlap (EEVO+NVO) can achieve engine-outlet temperature in excess of 255°C with 5.7% lower fuel consumption, 12% lower engine out NOx and 20% lower engine-out soot than the conventional thermal management strategy. Late exhaust valve opening with internal EGR via reinduction (LEVO+Reinduction) resulted in engine-outlet temperature in excess of 280°C, while meeting emission constraints at no fuel consumption penalty. This work also demonstrates that LEVO in conjunction with modulation of exhaust manifold pressure results in engine-outlet temperature in excess of 340°C while satisfying desired emission constraints. Aggressive use of LEVO can result in engine-outlet temperatures of 460°C, capable of active regeneration of DPF at curb idle, without the significant increase in engine-out soot emissions seen in previously studied strategies.

Attempted suicide term implies the person attempt suicide but survived the incident and admitted in the hospital for the treatment. The present study was conducted at G.M.C. Mumbai & Sir J. J. Hospital, Mumbai during 12 months period. The victims admitted as indoor patients were selected. A total 184 attempted suicide cases were studied. The patients were interviewed with information regarding age, sex, means of adopted attempted suicide and reason for attempting suicide. Female preponderance was observed in present study. Most common age was 21–30 years followed by 11-20 years. Means adopted by majority of attempted suicide cases was ingestion of poisonous substances. Most common reason for attempting suicide was family conflict reason followed by chronic illness.

Modern diesel engine aftertreatment systems require elevated temperatures for effective reduction of engine-out emissions. Maintaining elevated aftertreatment temperatures in a fuel-efficient manner is a challenge, especially at low-load engine operation where engine-outlet temperatures are low; therefore, higher engine-outlet temperatures are typically achieved via increased fuel consumption. Previous studies have demonstrated that strategies such as cylinder deactivation (method where there is neither valve motion nor fuel injection in a subset of cylinders, thereby isolating the deactivated cylinders from the gas exchange process) and cylinder cutout (method where there is no fuel injection in a subset of cylinders, implemented with high recirculated gas rates) reduce fuel consumption while elevating engine-outlet temperatures, by reducing the overall airflow through the engine. This article introduces and characterizes “non-fired cylinder ventilation” as alternate means to achieve fuel-efficient aftertreatment thermal management, by reduction of overall airflow through the engine. Fuel injection is deactivated from a subset of cylinders during non-fired cylinder ventilation, and the non-firing cylinders participate in the gas exchange process with the same manifold at a time, thereby reducing the intake-to-exhaust manifold gas exchange through the cylinders. It is demonstrated that non-fired cylinder ventilation shows similar fuel efficiency and thermal management as cylinder deactivation when the valves of the non-firing ventilated cylinders are open by at least 4 mm, due to similar, negligible, gas-exchange losses, while non-fired cylinder ventilation with lower valve lifts enables elevated engine-outlet temperatures with relatively higher fuel consumption than cylinder deactivation. Non-fired cylinder ventilation strategies demonstrate 75 °C higher temperatures at fuel-neutral conditions, and up to 35% fuel savings at similar temperatures, compared to six-cylinder operation.

Fuel-efficient aftertreatment thermal management in modern diesel engines is a difficult challenge, especially during low-load operation. This study explores the performance of cylinder deactivation in a diesel engine during low-load operation following highway cruise through experimental evaluation of two drive cycles, specifically extended idle and repeated heavy heavy-duty diesel truck creep cycles. Cylinder deactivation operations are shown to maintain comparable aftertreatment thermal management performance to conventional thermal management operation while reducing fuel up to 40% during extended idle operation. This fuel efficiency improvement coincides with engine-out emission reductions of 72% for soot and 52% for NOx. Cylinder deactivation also shows improved thermal management compared to a more fuel-efficient conventional operation.

This paper outlines a novel sensor selection and observer design algorithm for linear time-invariant systems with both process and measurement noise based on H2 optimization to optimize the tradeoff between the observer error and the number of required sensors. The optimization problem is relaxed to a sequence of convex optimization problems that minimize the cost function consisting of the H2 norm of the observer error and the weighted l1 norm of the observer gain. An LMI formulation allows for efficient solution via semi-definite programing. The approach is applied here, for the first time, to a turbo-charged spark-ignited engine using exhaust gas circulation to determine the optimal sensor sets for real-time intake manifold burnt gas mass fraction estimation. Simulation with the candidate estimator embedded in a high fidelity engine GT-Power model demonstrates that the optimal sensor sets selected using this algorithm have the best H2 estimation performance. Sensor redundancy is also analyzed based on the algorithm results. This algorithm is applicable for any type of modern internal combustion engines to reduce system design time and experimental efforts typically required for selecting optimal sensor sets.

Approximately 40% of typical heavy-duty vehicle operation occurs at loaded idle during which time conventional diesel engines are unable to maintain aftertreatment component temperatures in a fuel-efficient manner. Fuel economy and thermal management at this condition can be improved via reverse breathing, a novel method in which exhaust gases are recirculated, as needed, from exhaust to intake manifold via one or more cylinders. Resultant airflow reductions increase exhaust gas temperatures and decrease exhaust flow rates, both of which are beneficial for maintaining desirable aftertreatment component temperatures while consuming less fuel via reduced pumping work. Several strategies for implementation of reverse breathing are described in detail and are compared to cylinder deactivation and internal exhaust gas recirculation operation. Experimental data demonstrate 26% fuel consumption savings compared to conventional stay-warm operation, 60 °C improvement in turbine outlet temperature and 28% reduction in exhaust flow compared to conventional best fuel consumption operation at the loaded idle condition (800 r/min, 1.3 bar brake mean effective pressure). The incorporation of reverse breathing to more efficiently maintain desired aftertreatment temperatures during idle conditions is experimentally demonstrated to result in fuel savings of 2% over the heavy-duty federal test procedure drive cycle compared with conventional operation.

Cylinder deactivation has been recently demonstrated to have fuel savings and aftertreatment thermal management benefits at low to moderate loads compared to conventional operation in diesel engines. This study discusses dynamic cylinder activation as an effective variant to fixed diesel engine cylinder deactivation. The set of inactive and active cylinders varies on a cycle-by-cycle basis during dynamic cylinder activation. This enables greater control over forcing frequencies of the engine, thereby allowing the engine to operate away from the drivetrain resonant frequency at all engine speeds, while maintaining similar fuel savings, thermal management, and emission characteristics as fixed cylinder deactivation. Additional benefits of dynamic cylinder activation include a reduction in the consecutive number of cycles a given cylinder is deactivated, and more even cylinder usage. Enablement of engine operation without exciting drivetrain resonant frequencies at similar fuel efficiency and emissions as fixed cylinder deactivation makes dynamic cylinder activation a strong candidate to augment the benefits already demonstrated for fixed cylinder deactivation.

A large fraction of diesel engine tailpipe NOx emissions are emitted before the aftertreatment components reach effective operating temperatures. As a result, it is essential to develop technologies to accelerate initial aftertreatment system warm-up. This study investigates the use of early exhaust valve opening (EEVO) and its combination with negative valve overlap to achieve internal exhaust gas recirculation (iEGR), for aftertreatment thermal management, both at steady state loaded idle operation and over a heavy-duty federal test procedure (HD-FTP) drive cycle. The results demonstrate that implementing EEVO with iEGR during steady state loaded idle conditions enables engine outlet temperatures above 400 °C, and when implemented over the HD-FTP, is expected to result in a 7.9% reduction in tailpipe-out NOx.

Approximately 30% of the fuel consumed during typical heavy-duty vehicle operation occurs at elevated speeds with low-to-moderate loads below 6.5 bar brake mean effective pressure. The fuel economy and aftertreatment thermal management of the engine at these conditions can be improved using conventional means as well as cylinder deactivation and intake valve closure modulation. Airflow reductions result in higher exhaust gas temperatures, which are beneficial for aftertreatment thermal management, and reduced pumping work, which improves fuel efficiency. Airflow reductions can be achieved through a reduction of displaced cylinder volume by using cylinder deactivation and through reduction of volumetric efficiency by using intake valve closure modulation. This paper shows that, depending on load, cylinder deactivation and intake valve closure modulation can be used to reduce the fuel consumption between 5% and 25%, increase the rate of warm-up of aftertreatment, maintain higher temperatures, or achieve active diesel particulate filter regeneration without requiring dosing of the diesel oxidation catalyst.

Cylinder deactivation can be implemented at low loads in diesel engines to improve efficiency and aftertreatment thermal management through reductions in pumping work and airflow, respectively. The rate of increase of torque/power during diesel engine transients is limited by the engine’s ability to increase the airflow quickly enough to allow sufficient fuel addition to meet the desired torque/power. The reduced airflow during cylinder deactivation needs to be managed properly so as to not slow the torque/power response. This paper demonstrates that it is possible to operate a diesel engine at low loads in cylinder deactivation without compromising its transient torque/power capabilities, a key finding in enabling the practical implementation of cylinder deactivation in diesel engines.

Strict emissions regulations are mandated by the environmental protection agency (EPA) to reduce emission of greenhouse gases and criteria air pollutants from diesel engines, which are widely used in commercial vehicles. A ten-fold reduction in allowable heavy-duty on-road oxides of nitrogen (NOx) emissions are projected to be enforced by 2024. The need to meet these emission regulations, along with consumer demand for better fuel efficiency, has resulted in greater effort towards cleaner and more efficient diesel engines.Diesel engine aftertreatment systems are effective in reducing engine-out emissions, but only at catalyst bed temperatures above 200°C. The aftertreatment system needs to be quickly warmed up to its efficient operating temperatures, and maintain elevated temperatures in a fuel-efficient manner, which is a challenge using conventional engine strategies. This study details the use of advanced gas-exchange management, via variable valve actuation, to improve both `warm-up' and `stay-warm' aftertreatment thermal management.Fast initial warm-up of the aftertreatment system, following a cold engine start, is enabled by strategies such as early exhaust valve opening (EEVO), internal exhaust gas recirculation (iEGR) and late intake valve closure (LIVC). Steady state and drive cycle results of a combination of EEVO and iEGR at idle operation, and a combination of EEVO and LIVC at off-idle conditions below 7.6 bar BMEP, are presented. It is demonstrated that ~ 150°C higher steady state temperatures are achieved at idle, and up to 10.1% reduction in predicted tailpipe-out NOx is achieved at 3.1% fuel penalty over the heavy-duty federal test procedure (HD-FTP) drive cycle.Fuel-efficient `stay-warm' aftertreatment thermal management is demonstrated to be effectively achieved via cylinder deactivation (CDA), to reduce fuel consumption, elevate engine-outlet temperatures and reduce exhaust flow rates at idle and low load engine operation. Implementation of CDA at idle and low loads below 3 bar BMEP is demonstrated to achieve fuel savings of 4% over the HD-FTP drive cycle, while maintaining similar levels of tailpipe-out NOx emissions. It is demonstrated that lower air flow during CDA at, and near, idle operation does not compromise the transient torque/power capabilities of the engine- a key nding in enabling the practical implementation of CDA in diesel engines.Some of the practical challenges expected with CDA are studied in detail, and alternate strategies addressing the challenges are introduced. Dynamic cylinder activation (DCA) is introduced as a means to enable greater control over the torsional vibration characteristics of the engine, via selection of appropriate ring patterns, while maintaining similar performance and emissions as xed CDA. A generic strategy to use CDA and an appropriate DCA strategy to operate away from driveline resonant frequencies at different engine speeds is described. Ventilated cylinder cutout (VCC) is introduced as a means to potentially mitigate oil accumulation concerns during CDA, by ventilating the non- ring cylinders to the intake/exhaust manifold(s) by opening the intake/exhaust valves during all the four strokes of the engine cycle. The fuel efficiency and thermal management performance of VCC is assessed for different ventilation con gurations and compared with CDA and baseline engine operation.

Cylinder deactivation is a technique in multi-cylinder engines where the airflow and fuel injection are deactivated to a few of the total number of the cylinders such that the power demand is met by increasing fuel consumption in the remaining active cylinders. Diesel engine cylinder deactivation has been demonstrated to have fuel savings of 3.4% over heavy duty federal test procedure and approximately 4 – 35% fuel benefit is predicted over the port drayage cycle, while maintaining higher aftertreatment temperatures. Deactivation of cylinders can result in a decay in in-cylinder pressure via heat loss and blowby to the crankcase, which can lead to oil transport from the crankcase to the cylinder. Oil accumulation in the cylinders can deplete the lubricating oil faster and lead to misfiring or poor combustion when these cylinders are reactivated. This study involves the evaluation of different valvetrain strategies to address the issue of oil accumulation in the deactivated cylinders, while maintaining the benefits provided by cylinder deactivation. A commercial engine simulation software GT-Power, experimentally validated with experimental data, will be used in this study for simulation of the novel valvetrain strategies. The study will determine the effects and benefits of various intake and exhaust valve opening by varying the valve lifts, valve closing and opening timings for each of the two intake and two exhaust valves. The simulation results have shown that the valve strategies implemented have helped to maintain the incylinder pressures at around the atmospheric pressure in addition to maintaining the benefits of cylinder deactivation.

Vehicle emissions regulations are continuing to grow more challenging requiring near-zero levels of pollutant emissions. Nitric oxide (NOx) emissions are heavily regulated with the emission limit expected to become 1/10th of its present limit by 2021. In order to meet the new regulations, improvements in both the engine and the exhaust aftertreatment system are required. Exhaust gas recirculation (EGR) is used to reduce the NOx produced by the engine while the aftertreatment system converts most of the engine-out emissions to safer gases before releasing them to the atmosphere. One of the main challenges with the aftertreatment system is that it requires to operate at a certain minimum temperature before it is effective. Variable valve actuation (VVA) can be used to improve the thermal management of the aftertreatment system- first to accelerate the warmup following a cold start and then to maintain its temperature economically. Using VVA, negative valve overlap (NVO) was looked at as form of internal EGR, where exhaust gas is trapped inside the cylinder. Experiments showed a 70°C increase in exhaust gas temperature while maintaining engine out NOx. A literature survey was performed on exhaust gas re-induction as another means of internal EGR. Internal EGR has potential to be an effective means of reducing NOx and improving aftertreatment thermal efficiency in future diesel engines.