Stability Analysis and Identification of Superior Hybrids in Pearl Millet [Pennisetum glaucum (L.) R. Br.] Using the Multi Trait Stability Index.

Pearl millet stands as an important staple food and feed for arid and semi-arid regions of India and South Africa. It is also a quick supplier of important micronutrients like Fe and Zn via grain to combat micronutrient deficiencies among people in developing countries. India has notably spearheaded advancements in pearl millet production and productivity through the All India Coordinated Pearl Millet Improvement Project. There were 21 hybrids evaluated over arid and semi-arid ecologies of the western and southern regions of India. AMMI and GGE biplot models were adopted to recommend a specific hybrid for the particular locality. A joint analysis of variation indicated a significant genotype-environment interaction for most of the agronomical and grain micronutrient parameters. Pearson's correlation values dissected the significant and positive correlation among agronomic traits and the negative correlation with grain micronutrient traits. GGE biplot analysis recommended the SHT 106 as a dual-purpose hybrid and SHT 115 as a biofortified hybrid for the grain's Fe and Zn content. SHT 110 and SHT 108 were selected as stable and high grain yield-producing hybrids across all environments and specifically for E1, E2, and E4 as per the Which-Won-Where and What biplot. SHT 109 and SHT 103 hybrids were stable and high dry fodder yield-producing hybrids across all environments. In this study, the Multi-Trait Stability Index (MTSI) was employed to select the most stable and high-performing hybrids for all traits. It selected SHT 120, SHT 106, and SHT 104 for stability and great performance across all environments. These findings underscored the significance of tailored hybrid recommendations and the potential of pearl millet in addressing both food security and malnutrition challenges in various agro-ecological regions.

Long-term outcomes of ablation, liver resection, and liver transplant as first-line treatment for solitary HCC of 3 cm or less using an intention-to-treat analysis: A retrospective cohort study.

Background: Curative-intent therapies for hepatocellular carcinoma (HCC) include radiofrequency ablation (RFA), liver resection (LR), and liver transplantation (LT). Controversy exists in treatment selection for early-stage tumours. We sought to evaluate the oncologic outcomes of patients who received either RFA, LR, or LT as first-line treatment for solitary HCC ≤ 3 cm in an intention-to-treat analysis. Materials and methods: All patients with solitary HCC ≤ 3 cm who underwent RFA, LR, or were listed for LT between Feb-2000 and Nov-2018 were analyzed. Cox regression analysis was then performed to compare intention-to-treat (ITT) survival by initial treatment allocation and disease-free survival (DFS) by treatment received in patients eligible for all three treatments. Results: A total of 119 patients were identified (RFA n = 83; LR n = 25; LT n = 11). The overall intention-to-treat survival was similar between the three groups. The overall DFS was highest for the LT group. This was significantly higher than RFA (p = 0.02), but not statistically significantly different from LR (p = 0.14). After multivariable adjustment, ITT survival was similar in the LR and LT groups relative to RFA (LR HR:1.13, 95%CI 0.33-3.82; p = 0.80; LT HR:1.39, 95%CI 0.35-5.44; p = 0.60). On multivariable DFS analysis, only LT was better relative to RFA (LR HR:0.52, 95%CI 0.26-1.02; p = 0.06; LT HR:0.15, 95%CI 0.03-0.67; p = 0.01). Compared to LR, LT was associated with a numerically lower hazard on multivariable DFS analysis, though this did not reach statistical significance (HR 0.30, 95%CI 0.06-1.43; p = 0.13). Conclusion: For treatment-naïve patients with solitary HCC ≤ 3 cm who are eligible for RFA, LR, and LT, adjusted ITT survival is equivalent amongst the treatment modalities, however, DFS is better with LR and LT, compared with RFA. Differences in recurrence between treatment modalities and equipoise in ITT survival provides support for a future prospective trial in this setting.

The effects of cesium lead bromide quantum dots on the performance of copper phthalocyanine-based organic field-effect transistors.

Highly luminescent all-inorganic cesium lead bromide (CsPbBr3) perovskite quantum dots (QDs) have been extensively used as a photosensitizer in optoelectronic devices, while p-type small-organic-molecule copper phthalocyanine (CuPc) is also widely used as a photoactive material in solar cells, organic field-effect transistors (OFETs), etc. In this paper, we report the preparation of a CsPbBr3-QDs/CuPc heterostructure to study the effect of CsPbBr3-QDs on CuPc. The optical properties of both CuPc and the QDs/CuPc heterostructure were compared and contrasted using UV-vis absorbance and photoluminescence (PL) measurements. Furthermore, to study their electronic and charge transfer features, we fabricated field-effect transistors (FETs) on both pristine CuPc and QDs/CuPc heterostructure thin films and studied their photoresponsive electrical characteristics. Both pristine and QDs/CuPc-based FETs showed an enhancement in current and carrier mobility under illumination. The enhancement in the current and carrier mobility of the QDs/CuPc-based FETs is due to a large number of photoexcited charge carriers. We also observed that the current and carrier mobility in the QDs/CuPc heterostructure-based FET were lower than those of the pristine CuPc-based FET. This can be explained by the n-type doping effect of CsPbBr3 QDs on CuPc, which reduces the accumulation of holes in the active p-channel near the insulating layer and causes charge to be transferred from the QDs to the CuPc. Thus, we have observed a charge transfer effect in the CsPbBr3 QDs/CuPc heterostructure, which can be used in optoelectronic devices.

Early presentation of ruptured post-traumatic hepatic artery pseudoaneurysm.

Visceral artery aneurysms (VAA) are an uncommon but well recognized condition. Hepatic artery aneurysms (HAA) represent 14-20% of all visceral artery aneurysms. Post traumatic hepatic artery pseudoaneurysm is an uncommon delayed complication of blunt liver trauma. Here we present a case of a 27 year old male with blunt abdominal trauma who developed a post traumatic pseudoaneurysm of the hepatic artery just proximal to its bifurcation into the left and right branches. The pseudoaneurysm ruptured within 12 hours of injury and he required double ligation of the hepatic artery as well as right and left hepatic arteries . However, the bleeding continued through the retrograde flow from the gastroduodenal artery and hence, ligation of gastrodudenal artery was also done. The decision of complete devasularisation of liver was taken as an emergency lifesaving procedure. The patient recovered and was discharged without sequel.

Incidence of clinically suspected venous thromboembolism in British Indian patients.

Introduction Venous thromboembolism (VTE) remains a major public health issue around the world. Ethnicity is known to alter the incidence of VTE. To our knowledge, there are no reports in the literature investigating the incidence of VTE in British Indians. The aim of this study was to investigate the rates of symptomatic VTE in British Indian patients in the UK. Methods Patients referred to our institution between January 2011 and August 2013 with clinically suspected VTE were eligible for inclusion in the study. Those not of British Indian or Caucasian ethnicity were excluded. A retrospective review of these two cohorts was conducted. Results Overall, 15,529 cases were referred to our institution for suspected VTE. This included 1,498 individuals of British Indian ethnicity. Of these, 182 (12%) had confirmed VTE episodes. A further 13,159 of the patients with suspected VTE were coded as Caucasian, including 2,412 (16%) who had confirmed VTE events. VTE rates were a third lower in British Indians with clinically suspected VTE than in the equivalent Caucasian group. The British Indian cohort presented with VTE at a much earlier age than Caucasians (mean 57.0 vs 68.0 years). Conclusions This study suggests that British Indian patients have a lower incidence of VTE and are more likely to present at an earlier age than Caucasians. There was no significant difference in VTE type (deep vein thrombosis vs pulmonary embolism) among the ethnic groups. Clinicians should be aware of variations within ethnicities but should continue to adhere to existing VTE prevention guidance.

Prolonged Survival Following Pig-to-Primate Liver Xenotransplantation Utilizing Exogenous Coagulation Factors and Costimulation Blockade.

Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers. Baboon 2 was euthanized following a seizure on POD 5, despite normal liver function tests (LFTs) and no apparent pathology. Baboon 3 demonstrated initial stable liver function but was euthanized on POD 8 because of worsening LFTs. Pathology revealed C4d positivity, extensive hemorrhagic necrosis, and a focal cytomegalovirus inclusion. Baboon 4 was clinically well with stable LFTs until POD29, when euthanasia was again necessitated by plantar ulcerations and rising LFTs. Final pathology was C4d negative and without evidence of rejection, inflammation, or thrombotic microangiopathy. Thus, nearly 1-mo rejection-free survival has been achieved following LXT in two of four consecutive recipients, demonstrating that the porcine liver can support life in primates for several weeks and has encouraging potential for clinical application as a bridge to allotransplantation for patients with acute-on-chronic or fulminant hepatic failure.

Klotho and smoking--An interplay influencing the skeletal muscle function deficits that occur in COPD.

BACKGROUND: Klotho is an 'anti-ageing' hormone and transmembrane protein; Klotho deficient mice develop a similar ageing phenotype to smokers including emphysema and muscle wasting. The objective of this study was to evaluate skeletal muscle and circulating Klotho protein in smokers and COPD patients and to relate Klotho levels to relevant skeletal muscle parameters. We sought to validate our findings by undertaking complimentary murine studies. METHODS: Fat free mass, quadriceps strength and spirometry were measured in 87 participants (61 COPD, 13 'healthy smokers' and 13 never smoking controls) in whom serum and quadriceps Klotho protein levels were also measured. Immunohistochemistry was performed to demonstrate the location of Klotho protein in human skeletal muscle and in mouse skeletal muscle in which regeneration was occurring following injury induced by electroporation. In a separate study, gastrocnemius Klotho protein was measured in mice exposed to 77 weeks of smoke or sham air. RESULTS: Quadriceps Klotho levels were lower in those currently smoking (p = 0.01), irrespective of spirometry, but were not lower in patients with COPD. A regression analysis identified current smoking status as the only independent variable associated with human quadriceps Klotho levels, an observation supported by the finding that smoke exposed mice had lower gastrocnemius Klotho levels than sham exposed mice (p = 0.005). Quadriceps Klotho levels related to local oxidative stress but were paradoxically higher in patients with established muscle wasting or weakness; the unexpected relationship with low fat free mass was the only independent association. Within locomotor muscle, Klotho localized to the plasma membrane and to centralized nuclei in humans and in mice with induced muscle damage. Serum Klotho had an independent association with quadriceps strength but did not relate to quadriceps Klotho levels or to spirometric parameters. CONCLUSIONS: Klotho is expressed in skeletal muscle and levels are reduced by smoking. Despite this, quadriceps Klotho protein expression in those with established disease appears complex as levels were paradoxically elevated in COPD patients with established muscle wasting. Whilst serum Klotho levels were not reduced in smokers or COPD patients and were not associated with quadriceps Klotho protein, they did relate to quadriceps strength.

The Impact of Hydroxyethyl Starch Use in Deceased Organ Donors on the Development of Delayed Graft Function in Kidney Transplant Recipients: A Propensity-Adjusted Analysis.

Our objective was to evaluate the impact of hydroxyethyl starch (HES) use in organ donors after neurologic determination of death (DNDD) on recipient renal graft outcomes. The following data elements were prospectively collected for every DNDD managed by a single organ procurement organization from June 2011 to July 2013: demographics; critical care endpoints; treatments, including the use of HES; graft cold ischemia time (CIT); and the occurrence of recipient delayed graft function (DGF, dialysis in the first week after transplantation). Logistic regression was performed to identify independent predictors of DGF with a p-value <0.05. The results were then adjusted for each donor's calculated propensity to receive HES. Nine hundred eighty-six kidneys were transplanted from 529 donors. Forty-two percent received HES (1217 ± 528 mL) and 35% developed DGF. Kidneys from DNDDs who received HES had a higher crude rate of DGF (41% vs. 31%, p < 0.001). After accounting for the propensity to receive HES, independent predictors of DGF were age (OR 1.02 [1.01-1.04] per year), CIT (OR 1.04[1.02-1.06] per hour), creatinine (OR 1.5 [1.32-1.72] per mg/dL) and HES use (OR 1.41 [1.02-1.95]). HES use during donor management was independently associated with a 41% increase in the risk of DGF in kidney transplant recipients.

A comparison of patient-reported outcome measures after spinal surgery.

Minimal clinically important differences (MCID) in the scores of patient-reported outcome measures allow clinicians to assess the outcome of intervention from the perspective of the patient. There has been significant variation in their absolute values in previous publications and a lack of consistency in their calculation. The purpose of this study was first, to establish whether these values, following spinal surgery, vary depending on the surgical intervention and their method of calculation and secondly, to assess whether there is any correlation between the two external anchors most frequently used to calculate the MCID. We carried out a retrospective analysis of prospectively gathered data of adult patients who underwent elective spinal surgery between 1994 and 2009. A total of 244 patients were included. There were 125 men and 119 women with a mean age of 54 years (16 to 84); the mean follow-up was 62 months (6 to 199) The MCID was calculated using three previously published methods. Our results show that the value of the MCID varies considerably with the operation and its method of calculation. There was good correlation between the two external anchors. The global outcome tool correlated significantly better. We conclude that consensus needs to be reached on the best method of calculating the MCID. This then needs to be defined for each spinal procedure. Using a blanket value for the MCID for all spinal procedures should be avoided.

Dashboard (in the) knee.

We present the case of a 19-year-old individual presenting to an orthopaedic outpatient clinic several months following a dashboard knee injury during a road traffic accident with intermittent mechanical symptoms. Despite unremarkable examination findings and normal magnetic resonance imaging, the patient was identified subsequently as having an intra-articular plastic foreign body consistent with a piece of dashboard on arthroscopic knee assessment, the retrieval of which resulted in a complete resolution of symptoms.

Strabismus genetics across a spectrum of eye misalignment disorders.

Eye misalignment, called strabismus, is amongst the most common phenotypes observed, occurring in up to 5% of individuals in a studied population. While misalignment is frequently observed in rare complex syndromes, the majority of strabismus cases are non-syndromic. Over the past decade, genes and pathways associated with syndromic forms of strabismus have emerged, but the genes contributing to non-syndromic strabismus remain elusive. Genetic testing for strabismus risk may allow for earlier diagnosis and treatment, as well as decreased frequency of surgery. We review human and model organism literature describing non-syndromic strabismus, including family, twin, linkage, and gene expression studies. Recent advances in the genetics of Duane retraction syndrome are considered, as relatives of those impacted show elevated familial rates of non-syndromic strabismus. As whole genome sequencing efforts are advancing for the discovery of the elusive strabismus genes, this overview is intended to support the interpretation of the new findings.

Evidence of ancillary trigeminal innervation of levator palpebrae in the general population.

The cranial synkineses are a group of disorders encompassing a variety of involuntary co-contractions of the facial, masticatory, or extraocular muscles that occur during a particular volitional movement. The neuroanatomical pathways for synkineses largely remain undefined. Our studies explored a normal synkinesis long observed in the general population - that of jaw opening during efforts to open the eyelids widely. To document this phenomenon, we observed 186 consecutive participants inserting or removing contact lenses to identify jaw opening. Seeking electrophysiological evidence, in a second study we enrolled individuals undergoing vascular decompression for trigeminal neuralgia or hemifacial spasm, without a history of jaw-winking, ptosis, or strabismus, to record any motor responses in levator palpebrae superioris (LPS) upon stimulation of the trigeminal motor root. Stimulus was applied to the trigeminal motor root while an electrode in levator recorded the response. We found that 37 participants (20%) opened their mouth partially or fully during contact lens manipulation. In the second study, contraction of LPS with trigeminal motor stimulation was documented in two of six patients, both undergoing surgery for trigeminal neuralgia. We speculate these results might provide evidence of an endogenous synkinesis, indicating that trigeminal-derived innervation of levator could exist in a significant minority of the general population. Our observations demonstrate plasticity in the human cranial nerve innervation pattern and may have implications for treating Marcus Gunn jaw-winking.

The impact of meeting donor management goals on the development of delayed graft function in kidney transplant recipients.

Many organ procurement organizations (OPOs) utilize preset critical care endpoints as donor management goals (DMGs) in order to standardize care and improve outcomes. The objective of this study was to determine the impact of meeting DMGs on delayed graft function (DGF) in renal transplant recipients. All eight OPOs of the United Network for Organ Sharing Region 5 prospectively implemented nine DMGs in every donor after neurologic determination of death (DNDD). "DMGs met" was defined a priori as achieving any seven of the nine DMGs and this was recorded at the time of consent for donation to reflect donor hospital ICU management, 12-18 h later, and prior to organ recovery. Multivariable analyses were performed to identify independent predictors of DGF (dialysis in the first week after transplantation) with a p<0.05. A total of 722 transplanted kidneys from 492 DNDDs were included. A total of 28% developed DGF. DMGs were met at consent in 14%, 12-18 h in 32% and prior to recovery in 38%. DGF was less common when DMGs were met at consent (17% vs. 30%, p=0.007). Independent predictors of DGF were age, Cr and cold ischemia time, while meeting DMGs at consent was significantly protective. The management of potential organ donors prior to consent affects outcomes and should remain a priority in the intensive care unit.

A comparative study of the outcomes of primary and revision lumbar discectomy surgery.

The outcome of surgery for recurrent lumbar disc herniation is debatable. Some studies show results that are comparable with those of primary discectomy, whereas others report worse outcomes. The purpose of this study was to compare the outcome of revision lumbar discectomy with that of primary discectomy in the same cohort of patients who had both the primary and the recurrent herniation at the same level and side.A retrospective analysis of prospectively gathered data was undertaken in 30 patients who had undergone both primary and revision surgery for late recurrent lumbar disc herniation. The outcome measures used were visual analogue scales for lower limb (VAL) and back (VAB) pain and the Oswestry Disability Index (ODI).There was a significant improvement in the mean VAL and ODI scores (both p < 0.001) after primary discectomy. Revision surgery also resulted in improvements in the mean VAL (p < 0.001), VAB (p = 0.030) and ODI scores (p < 0.001). The changes were similar in the two groups (all p > 0.05).Revision discectomy can give results that are as good as those seen after primary surgery.

Are soft tissue measurements on lateral cervical spine X-rays reliable in the assessment of traumatic injuries?

INTRODUCTION: Traumatic neck pain is a common presentation to the emergency department. Lateral plain radiographs remain the primary investigation in the assessment of these injuries. Soft tissue assessment forms an integral component of these radiographs. They can provide information on subtle injuries that may not be obvious. Many methods are used to assess the prevertebral soft tissue shadows. The two more commonly used techniques include the 'seven at two and two at seven' rule (method 1) and the ratio of the soft tissues with respect to the vertebral width (method 2). AIM: To assess which of the above two methods in assessing cervical spine soft tissue shadows on lateral radiographs is more sensitive in the presence of cervical spine injuries. METHODS: A retrospective analysis of consecutive traumatic cervical spine films performed within a busy trauma tertiary centre over a period of 7 months. Patients were divided into two groups: group 1-fractures; group 2-no fractures. The prevertebral soft tissue shadows were measured at referenced points on the lateral cervical spine films with respect to the above two methods and comparisons between the groups were made. RESULTS: Thirty-nine patients in group 1 were compared to a control group of 60 patients in group 2. Both methods failed to identify any significant differences between the two groups. The sensitivity and specificity for method 1 was 7.6 and 93 %, and for method 2, they were 7.6 and 98 %, respectively. CONCLUSION: There is no significant difference between the soft tissue shadows when comparing patients with and without cervical spine fractures on lateral radiographs. Both commonly used measures of soft tissue shadows in clinical practice are insensitive in identifying patients with significant osseous injuries. They, therefore, do not offer any further value in interpreting traumatic cervical spine radiographs. The management of patients with cervical spine trauma in the absence of obvious osseous injury on standard radiographs should warrant a computed tomography (CT) scan if clinically indicated.

Epigenetic changes in hypothalamic appetite regulatory genes may underlie the developmental programming for obesity in rat neonates subjected to a high-carbohydrate dietary modification.

Earlier, we showed that rearing of newborn rats on a high-carbohydrate (HC) milk formula resulted in the onset of hyperinsulinemia, its persistence in the post-weaning period and adult-onset obesity. DNA methylation of CpG dinucleotides in the proximal promoter region and modifications in the N-terminal tail of histone 3 associated with the neuropeptide Y (Npy) and pro-opiomelanocortin (Pomc) genes were investigated to decipher the molecular mechanisms supporting the development of obesity in HC females. Although there were no differences in the methylation status of CpG dinucleotides in the proximal promoter region of the Pomc gene, altered methylation of specific CpG dinucleotides proximal to the transcription start site was observed for the Npy gene in the hypothalami of 16- and 100-day-old HC rats compared with their methylation status in mother-fed (MF) rats. Investigation of histone tail modifications on hypothalamic chromatin extracts from 16-day-old rats indicated decreased acetylation of lysine 9 in histone 3 (H3K9) for the Pomc gene and increased acetylation for the same residue for the Npy gene, without changes in histone methylation (H3K9) in both genes in HC rats. These findings are consistent with the changes in the levels of Npy and Pomc mRNAs in the hypothalami of HC rats compared with MF animals. Our results suggest that epigenetic modifications could contribute to the altered gene expression of the Npy and Pomc genes in the hypothalami of HC rats and could be a mechanism leading to hyperphagia and the development of obesity in adult female HC rats.

Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium.

The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems.

Does the use of a "track and trigger" warning system reduce mortality in trauma patients?

INTRODUCTION: Despite the lack of robust evidence, numerous different "track and trigger" warning systems have been implemented. These have only been validated in an emergency medical admissions setting. The Modified Early Warning Score (MEWS) is the chosen track and trigger system used in the University Hospitals of Leicester trauma unit, but has not been validated in trauma patients. A considerable proportion of all trauma admissions are elderly patients with proximal femoral fractures and significant co-morbidities. Early recognition of physiological deterioration and prompt action could therefore be lifesaving in this patient group. AIM: To identify whether the implementation of the MEWS system coupled with a critical care outreach service resulted in a reduction in mortality in a busy trauma unit. METHOD: A retrospective study. The MEWS system was implemented in all trauma and orthopaedic wards at the Leicester Royal Infirmary in the summer of 2005. The numbers of emergency trauma inpatient admissions and deaths from January 2002 to December 2009 were obtained. The diagnosis, primary procedures and cause of death, if known, were noted. Comparisons were made pre- and post-MEWS. Student's t-test was used for statistical analysis. RESULTS: 32,149 patients were admitted (55% male; 45% female). Overall there were 889 deaths (77% female; 33% male, P<0.0001). The in-hospital mortality rate for orthopaedic trauma patients was 2.8% throughout the 7-year study period. 61% of those who died were admitted with proximal femoral fractures. The modal age group with the highest mortality was 81-90 years. Overall, females had a considerably greater mortality rate than males. The mortality rate was lower post-MEWS in males (1.82-1.418%; P=0.214), females (4.871-3.364%; P=0.108) and all patients (3.215-2.294%; P=0.092), but this was not statistically significant. CONCLUSION: The use of a track and trigger warning system has not led to a statistically significant reduction in mortality in trauma patients. In view of the apparent lack of clinical effectiveness of the MEWS/outreach partnership, the cost effectiveness of this initiative needs to be questioned. Possible reasons for these findings include: failure of the MEWS to be correctly applied, inadequate action once the threshold is triggered, or unsuitability of this tool for this patient population. A better system for identifying and treating elderly, medically unwell trauma patients with co-morbidities needs to be developed.