An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks

Background: Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn). Results: We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. Conclusions: The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful

Energy for a sustainable road/rail transport system in India

The main motivation for this study is that the strong transport-energy nexus has not received the attention it deserves, though energy is a crucial constraint on transport, and transport is a major determinant of energy demand. Also, many detailed treatments of the transport sector have not scrutinised the sustainability of the present pattern of development of this sector. Further, the prevailing paradigm guiding the development of the sector is made explicit and critiqued because it is often the root cause of its unsustainability. And, because treatments of transport policy issues tend to proceed without a clear statement of underlying goals and strategies, the entire hierarchy of interventions - from goals to strategies to policies - has been discussed. Finally, an attempt has been made to deal with both the supply and demand aspects of the transport sector. The study is restricted to road and rail transport since air and water (inland waters, and coastal and international seas) transport handle very small fractions of domestic traffic demand. The detailed discussions are preceded by overviews of the main features of the Indian transport system as well as of the energy sector as pertaining to transport. It is suggested that the goal of the Indian transport sector should be an efficient, capital-saving, non-import-intensive, affordable, service-oriented and environmentally sound transport system, i.e., a sustainable transport system. A strategy or broad plan to achieve this goal of a sustainable transport system should consist of several components: (1) minimisation of dependence on petroleum fuels, (2) maximisation of the level of safe, comfortable and time-saving transport services, (3) maximisation of the environmental soundness of the transport system, and in particular, reduction of local and global environmental pollution, (4) minimisation of the capital requirements for the transport modal mix that should also include non-motorised transport (NMT), and (5) minimisation of the energy used by the transport system without a reduction of the services provided. The detailed policies (plans or courses of action) to implement the above strategies for achieving a sustainable transport system fall into the following categories: (1) transport-energy database generation and use, (2) demand management, (3) technological improvements in road transport, (4) improvement of the capacity and quality of road infrastructure, (5) traffic management, (6) improvement of the railways, (7) improvement of urban transport, (8) providing a niche for non-motorised modes of transport, (9) pollution control and abatement, (10) costing and pricing, (11) modal shifts to achieve a least-cost freight modal mix, (12) modal shifts to achieve a least-cost passenger modal mix, (13) solutions to the transport sector's problems through measures in other sectors, (14) alternative fuels. Appropriate policy instruments or mechanisms for initiating and maintaining the policies as well as suitable policy agents to wield the policy instruments have also been identified. The market has the power of being an excellent allocator of money, materials and manpower, but unfortunately also has definite limits - it is not very good at looking after the poor, the environment, the long-term and the infrastructure and national strategic concerns such as self-reliance and external debt, all of which are of crucial relevance to the transport system. Hence, the visible hand of government and the people must complement the invisible hand of the market. In conclusion, both short-term low-cost measures to attract political decision-makers with short time-horizons and long-term measures have been mentioned. The short-term measures consist mainly of better maintenance, better driving practices, optimal routing of buses, dedicated routes for buses with traffic restrictions on these dedicated routes, special lanes for slow traffic, supply constraint on personal vehicles, export orientation to the production of personal vehicles, removal of kerosene and diesel subsidies, no long-haul truck permits, increase of truck taxes and shift of passengers travelling less than 300 km from rail to bus. The long-term measures consist mainly of increases in fuel efficiency, introduction of lower-power bus engines, increases in number of buses and/or suburban trains, investments on mass transportation infrastructure, home electrification, improvement of rail freight operations, truck-rail freight linkage, introduction of CNG for urban fleets, switches to biomass-derived fuels for transportation, biomass-derived fuels as petrol and diesel extenders, silviculture for biomass-derived fuels, and alternative cooking fuels and/or devices to replace kerosene

Integrated energy planning: Part II. Examples of DEFENDUS scenarios

The first part of this paper presented an ab initio exposition of the development-focused end-use oriented service-directed (DEFENDUS) approach to energy planning. In this approach, the future demand for any source of energy is estimated on the basis of the energy services required and the efficiency with which these are provided. To meet this demand, the costs per unit of the available energy-supply/saving technologies are estimated and a least-cost mix of options identified. In this second part, some of the energy studies for which the DEFENDUS method has been used are described to demonstrate that its applicability is not confined to a particular region or source of energy. These studies include: electricity for five states of India, petroleum products for the country as a whole, biomass for the state of Karnataka, and a composite energy scenario for Karnataka involving integration of all the currently-used sources of energy. In every case, the energy usage pattern in the commencement year of the plan, i.e., the total energy usage disaggregated between the existing categories of users according to their end-uses, is obtained. Then, depending on the goals selected and the strategies that could be adopted to achieve them, growth rates for each category of users are used to estimate the number of users in future years. Improvement in the efficiency of end-use devices and/or substitution of energy sources are considered, to determine the possible reduction in the category-wise unit energy usage, and the corresponding energy requirement is estimated. The electricity plan for the state of Karnataka comprises future demand estimation as well as the comparative costs of various supply/saving options. For the other states, electricity demand has been estimated in various scenarios. In the oil scenarios for India, the focus is mainly on demand management through modal and carrier shifts, with emphasis on the middle distillates. The biomass strategy for Karnataka includes both demand- and supply-side measures. All these studies show that the DEFENDUS planning procedure is easily amenable to modification according to the particular case under consideration. Further, the integration of worksheets for individual sources of energy demonstrates that this method, though simple, is capable of dealing with composite energy planning. Above all, with the popularity of personal computers and spreadsheet packages, the DEFENDUS method facilitates the democratization of energy planning

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs.

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

Rasch-built overall disability scale for POEMS syndrome (POEMS-RODS)

Patient-reported outcome measures engage patients in disease severity measurement and the metrics reported can be meaningful to their lives. The Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes syndrome (POEMS) is a complex multisystem disorder with disabling neuropathy which is distinct from other acquired inflammatory neuropathies. No current POEMS-specific validated disability scales exist. To address this, we have produced a Rasch-built overall disability scale (RODS) specific to POEMS. A 146-item preliminary questionnaire containing relevant activity and participation items for neuropathic disability was applied to 49 clinically stable patients with POEMS from the UK national POEMS cohort. A total of 123 items not fulfilling Rasch model expectations were sequentially removed. The final 23-item POEMS-RODS fulfilled Rasch model expectations and showed acceptable test-retest reliability. The 23-item POEMS-RODS is a disease-specific patient-reported outcome measure able to detect activity limitations within the range of ability demonstrated by the UK POEMS cohort. Larger international studies are needed to confirm the broader applicability and responsiveness of this scale in other countries

Sensory Structures on the Antenniform Legs of Whip Spider, Phrynichus phipsoni (Arachnida, Amblypygi), from the Indian State of Goa: Scanning Electron Microscopic Elucidation

Amblypygi have a tropical and sub-tropical distribution and their first of the four pairs of legs, is modified as feelers. Their activity period and dark habitats render visual cues ineffective and they rely on non-visual sensory perception. There is agreement among researchers that the whip spiders invest in olfactory and tactile senses imparted by sensory structures concentrated on the tarsal segment of the first pair of long, well-articulated non-ambulatory legs that are constantly moved in all directions to sample the environment for detecting location of prey, as also for navigating. This is the first attempt to elucidate the sensory structures present on the antenniform legs of the whip spider, Phrynichus phipsoni (Pocock, 1894), collected from the state of Goa, India; using scanning electron micro[1]scope, and paves way for further research on sensory biology of this cryptic arachnid order. The examined specimen generally conforms to the diversity and morphology of sensory assemblage on the antenniform legs reported in other amblypygi species. Sensory structures elucidated include terminal trident tarsal claws, tarsal organ, bristles, porous sensilla, club sensilla, rod sensilla, slit sensilla, trichobothria, plate organ, pit organ and foliate leaf like hairs

Nerve biopsy in T-cell lymphoma with neurolymphomatosis: where and when

Peripheral T-cell lymphomas are rare heterogeneous haematological malignancies that may also involve peripheral nerves in a very small subset of cases. We report a patient with a diagnostically challenging cutaneous T-cell lymphoma and multifocal mononeuropathies in whom a targeted nerve biopsy identified lymphomatous infiltration of nerves and expedited combination treatment with chemotherapy and an autologous stem cell transplant. She showed an excellent response with a complete metabolic response on positron emission tomography imaging and significant clinical improvement, maintained 5 years post-treatment