The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future

A 10 Gb/s Passive-Components-based WDM-TDM Reconfigurable Optical Access Network Architecture

We propose a cost-effective, reconfigurable optical access network by employing passive components in the remote node and dual conventional optical transceivers in ONUs. The architecture is demonstrated with bidirectional transmission at 10 Gb/s

10Gb/s Bi-directional Symmetric WDM-PON System based on POLMUX Technique with Polarization Insensitive ONU

We demonstrated 10Gb/s bi-directional symmetric transmission based on polarizationdivision multiplexing with a centralized light source. One of two orthogonal polarization states carries downstream data while the other un-modulated state is used for upstream modulation

Performance evaluation of IR-UWB in short-range fiber communication using linear combination of monocycles

Abstract-We present the performance evaluation of impulse radio ultrawideband (IR-UWB) over fiber using a simple pulse design technique with a high fractional bandwidth. The technique, based on the linear combination of the first-order Gaussian derivatives with different pulse-shaping factors, shows full compliance with Federal Communications Commission mask requirements even in the most severely power-restricted GPS band. We validated our approach with experiments employing an intensity-modulation direct-detection scheme. The experimental setup uses a directly modulated DFB laser at 1302.56 nm and a multimode fiber-coupled photodetector with 24 m diameter photosensitive area. The transmission link consists of 25 km single-mode fiber or 4.4 km multimode fiber. Error-free transmission at 2 Gb/s is achieved over both fiber links. The result shows the proposed pulse-generation technique to be simple and cost-effective compared to higher order Gaussian derivative schemes. This can be implemented successfully to distribute UWB signals over optical links for access and in-building networks. Index Terms-Impulse radio (IR), in-building network, signal processing, ultrawideband (UWB) communications

Perceptions and utilization of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine in young children in the Chikhwawa District of Malawi: a mixed methods study

Background Adherence to anti-malarial dosing schedules is essential to ensure effective treatment. Measuring adherence is challenging due to recall issues and the participants’ awareness of the desired behaviour influencing their actions or responses. This study used qualitative methods, which allow for rapport building, to explore issues around anti-malarial utilization in young children, and used the results to guide the development of a context specific questionnaire on perceptions and adherence to artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ). Methods Qualitative data collection included 12 focus group discussions which explored community perceptions of anti-malarials and experiences of administering medications to children. Critical incidence interviews were conducted with 22 caregivers to explore experiences of administering the dispersible or original formulation of AL to young children during recent febrile episodes. A structured questionnaire was used to gather data on experience of recent treatment and adherence to anti-malarials during follow-up visits with 218 caregivers whose child was recently treated with either dispersible AL or DHA-PPQ. Discussion/Conclusion Caregivers experience great difficulty in administering medication to children. While the sweet taste of dispersible AL may have reduced conflict between the child and caregiver, sub-optimal dosing due to medication loss remained a problem and overall adherence was greater among those receiving DHA-PPQ, which requires fewer doses. Some caregivers were found to deliberately alter the dosing schedule according to whether they perceived the medication to be too weak or strong. They also developed theories for poor treatment outcomes, such as attributing this to lack of compatibility between the medication and the child. Health education messages should be strengthened to ensure a combination of clear pictorial and verbal instructions are used during dispensing, and consequences of under and over-dosing are explained alongside appropriate responses to possible adverse events. Further optimizing of anti-malarial adherence among children requires the development of anti-malarials with pharmacological properties that allow user-friendly administration and simplified dosing schedules

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients