Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell-cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells and cerebral organoids, supporting the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells reshaped the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.

Translational fidelity screens in mammalian cells reveal eIF3 and eIF4G2 as regulators of start codon selectivity.

The translation initiation machinery and the ribosome orchestrate a highly dynamic scanning process to distinguish proper start codons from surrounding nucleotide sequences. Here, we performed genome-wide CRISPRi screens in human K562 cells to systematically identify modulators of the frequency of translation initiation at near-cognate start codons. We observed that depletion of any eIF3 core subunit promoted near-cognate start codon usage, though sensitivity thresholds of each subunit to sgRNA-mediated depletion varied considerably. Double sgRNA depletion experiments suggested that enhanced near-cognate usage in eIF3D depleted cells required canonical eIF4E cap-binding and was not driven by eIF2A or eIF2D-dependent leucine tRNA initiation. We further characterized the effects of eIF3D depletion and found that the N-terminus of eIF3D was strictly required for accurate start codon selection, whereas disruption of the cap-binding properties of eIF3D had no effect. Lastly, depletion of eIF3D activated TNFα signaling via NF-κB and the interferon gamma response. Similar transcriptional profiles were observed upon knockdown of eIF1A and eIF4G2, which also promoted near-cognate start codon usage, suggesting that enhanced near-cognate usage could potentially contribute to NF-κB activation. Our study thus provides new avenues to study the mechanisms and consequences of alternative start codon usage.

In-hospital outcomes of paediatric burn injuries managed in children's hospitals compared to general hospitals.

INTRODUCTION: In Australia and New Zealand, children with burn injuries are cared for in either general hospitals which cater to both adult and paediatric burn injuries or in children's hospitals. Few publications have attempted to analyse modern burn care and outcomes as a function of treating facilities. AIM: The aim of this study was to compare in-hospital outcomes of paediatric burn injuries managed in children's hospitals to those treated in general hospitals that regularly treated both adult and paediatric burn patients. METHODS: A retrospective cohort study of cases was undertaken using data from the Burns Registry of Australia and New Zealand (BRANZ). All paediatric patients with data for an acute or transfer admission to a BRANZ hospital and registered with BRANZ with a date of admission between 1 July 2016 and 30 June 2020 were included in the study. The primary outcome of interest was the acute admission length of stay. Secondary outcome measures of interest included admission to the intensive care unit and readmission to a specialist burn service within 28 days. The Alfred Hospital Ethics Committee granted ethical approval for this study (project 629/21). RESULTS: A total of 4630 paediatric burn patients were included in the analysis. Approximately three quarters of this cohort (n = 3510, 75.8%) were admitted to a paediatric only hospital, while the remaining quarter (n = 1120, 24.2%) were admitted to a general hospital. A greater proportion of patients admitted to general hospitals underwent burn wound management procedures in the operating theatre (general hospitals 83.9%, children's hospitals 71.4%, p < 0.001). Patients admitted to children's hospitals had a longer median time to their first episode of grafting (children's hospitals 12.4 days, general hospitals 8.3 days, p < 0.001). The adjusted regression model for hospital LOS indicate that patients admitted to general hospitals had a 23% shorter hospital LOS, compared to patients admitted to children's hospitals. Neither the unadjusted or adjusted model for intensive care unit admission was significant. After accounting for relevant confounding factors, there was no association between service type and hospital readmission rates. CONCLUSIONS: Comparing children's hospitals and general hospitals, different models of care seem to exist. Burn services in children's hospitals adopted a more conservative approach and were more inclined to facilitate healing by secondary intention rather than surgical debridement and grafting. General hospitals are more "aggressive" in managing burn wounds in theatre early, and debriding and grafting the burn wounds whenever considered necessary.

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether changes in human cells alter requirements for essential genes. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells, providing support for the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells can reshape the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.

Burn Wound Bed Management.

Critical to the success of modern burn care is the management of the burn wound. Timely and complete removal of nonviable tissue is complicated by the irreplaceable nature of the tissue lost either through the burn injury or as "collateral damage" as part of the treatment. Challenges in distinguishing between viable and nonviable tissue and "replacing the irreplaceable" are discussed alongside potential disruptive technologies which could fundamentally change how burn care is delivered. Advances in burn wound bed management forms the foundation on which the goal of zero preventable death and disability after burn injury can be achieved.

Burn Lessons Learned From the Whakaari White Island Volcanic Eruption.

New Zealand's most active volcano, Whakaari White Island was a common tourist attraction prior to its eruption on December 9, 2019. At the time of the eruption, there were 47 people on the island from 3 tour groups. Thirty-nine people survived the initial eruption and were extracted. Thirty-one entered into the New Zealand National Burn Service across four hospitals. The median age of the patients treated at the National Burn Centre was 45.5 years (range: 14-67 years) and median TBSA burn was 49.5% (range: 9%-90%). The 3-month survival of this eruptive event was 55%, which subsequently fell to an overall rate of 53% following one late death of an early survivor after repatriation home. Of the patients who survived the initial eruption for long enough to be admitted to the National Burn Service, the overall survival rate was 71% at 3 months. We describe 12 lessons we have learnt from our management of the survivors. The key surgical lessons among these are: 1) The injuring mechanism combined ballistic trauma, thermal and acidic burn components, with the acid component being the most problematic and urgent for management; 2) Volcanic ash burns result in ongoing burn depth progression, deep underlying tissue damage and significant metabolic instability; 3) Early skin grafting was not successful in many cases; 4) Reconstructive strategy needed adjusting to cope with the high operative demand and limited donor sites in all patients; 5) Protect yourself from potential dangers with additional personal protective equipment in an unfamiliar setting.

Determining the Independent Risk Factors for Worse SCAR-Q Scores and Future Scar Revision Surgery.

BACKGROUND: Scar revisions have been increasing in number. Patient-reported outcome measures are one tool to aid scar modulation decision-making. The aims of this study were to determine patient, scar, and clinical risk factors for (1) low SCAR-Q Appearance, Symptom, and Psychosocial Impact scores and how this differs for children; and (2) the potential need for future scar revision surgery to better identify such patients in a clinical setting. METHODS: A multicenter international cross-sectional cohort study based on survey data of participants with traumatic, surgical, and burn scars attending plastic, hand, and burn clinics in four countries was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Univariate analysis to identify risk factors and multivariable logistic analysis to select risk factors were completed. Collinearity for nonindependent factors and C statistic for model discrimination were also calculated. RESULTS: Seven hundred thirty-one participants completed the study booklet, and 546 participants (74.7 percent) had full data. Independent risk factors were determined to be a bothersome scar and perception of scarring badly for all three scales. Risk factors for self-reporting the need for future surgery included a health condition, scarring badly, scar diagnosis, prior scar revision, and low Psychosocial Impact scores. We did not identify evidence of multicollinearity. C statistics were high (0.81 to 0.84). CONCLUSIONS: This study is the first multicenter international study to examine independent risk factors for low patient-reported outcome measure scores and the potential need for future scar revision surgery. Patients that perceive themselves as scarring badly and having a bothersome scar were at a higher risk of scar appearance concern, an increased symptom burden, and poorer psychosocial impact scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Comparison of Predictive Model of Care Requirements for Burn Patients With Operative Requirements Following Volcanic Burns.

On December 9, 2019, Whakaari/White Island volcano in New Zealand erupted with 47 people on the island. Thirty-one people survived long enough to enter the New Zealand National Burn network-13 were repatriated to Australia within 72 hours and 14 of the remaining 18 were treated at the National Burn Center at Middlemore Hospital in Auckland. Our department has previously published a model to calculate the total operative requirements for any given burn surface area for the first 4 weeks of burn treatment. From this model, we calculated the predicted surgical time and operative visit requirements for each patient and compared this to their actual requirements. Actual requirements were also recorded beyond 4 weeks until discharge. Results show that the average variance for operative minutes was significantly above predicted with both the full-thickness burn model (average variance 3.24) and the electrical burn model (average variance 2.65). There was a wide range in both cases (0.54-6.17 and 0.44-5.06, respectively). There was less variance from predicted values of operative visits required than operative minutes (mean: 1.58; range 0.9-3.02). Overall, the values for patients with smaller burns showed the greatest variability from predictions with regard to the total number of operative visits during the first 4 weeks of care. Additionally, patients with burn size greater than 50% TBSA required significant theater access beyond 4 weeks. Analysis of these findings will assist with future planning in both disaster and non-disaster settings in the provision of burn care.

Psychometric Findings for the SCAR-Q Patient-Reported Outcome Measure Based on 731 Children and Adults with Surgical, Traumatic, and Burn Scars from Four Countries.

BACKGROUND: Each year, millions of individuals develop scars secondary to surgery, trauma, and/or burns. Scar-specific patient-reported outcome measures to evaluate outcomes are needed. To address the gap in available measures, the SCAR-Q was developed following international guidelines for patient-reported outcome measure development. This study field tested the SCAR-Q and examined its psychometric properties. METHODS: Patients aged 8 years and older with a surgical, traumatic, and/or burn scar anywhere on their face or body were recruited between March of 2017 and April of 2018 at seven hospitals in four countries. Participants answered demographic and scar questions, the Fitzpatrick Skin Typing Questionnaire, the Patient and Observer Scar Assessment Scale (POSAS), and the SCAR-Q. Rasch measurement theory was used for the psychometric analysis. Cronbach's alpha, test-retest reliability, and concurrent validity were also examined. RESULTS: Consent was obtained from 773 patients, and 731 completed the study. Participants were aged 8 to 88 years, and 354 had surgical, 184 had burn, and 199 had traumatic scars. Analysis led to refinement of the SCAR-Q Appearance, Symptoms, and Psychosocial Impact scales. Reliability was high, with person separation index values of 0.91, 0.81, and 0.79; Cronbach alpha values of 0.96, 0.91, and 0.95; and intraclass correlation coefficient values of 0.92, 0.94, and 0.88, respectively. As predicted, correlations between POSAS scores and the Appearance and Symptom scales were higher than those between POSAS and Psychosocial Impact scale scores. CONCLUSIONS: With increasing scar revisions, a scar-specific patient-reported outcome measure is needed to measure outcomes that matter to patients from their perspective. The SCAR-Q represents a rigorously developed, internationally applicable patient-reported outcome measure that can be used to evaluate scars in research, clinical care, and quality improvement initiatives.

A consecutive case series of defects reconstructed using NovoSorbⓇ Biodegradable Temporising Matrix: Initial experience and early results.

BACKGROUND: NovoSorbⓇ Biodegradable Temporising Matrix (BTM) is a synthetic dermal template recently approved for treatment of full thickness defects of the skin. It requires a two-stage reconstruction where it is initially placed into a defect to generate a neodermis, which is later covered by a split skin graft. It has previously been described for the treatment of acute full thickness burn injury, necrotising fasciitis and free flap donor site reconstruction. METHODS: A consecutive case series review of patients treated with BTM at Middlemore Hospital was performed. Patient demographics, defect aetiology, indications for dermal matrix use, surgical details, and complications were recorded using information gathered from the medical records. RESULTS: This case series included 25 patients with a range of defects resulting from acute full thickness burn injury, burn scar revision, necrotising soft-tissue infection, tumour excision and traumatic loss. In these patients, 72% of wounds were identified as complex defects with exposed bone or tendon. Complications encountered included infection, non-adherence and incomplete vascularisation. CONCLUSION: BTM provided a good reconstructive option for a wide range of defects, many of which were not amenable to immediate skin grafting. Once vascularised and ready for the second stage, it developed a red-pink colour and demonstrated capillary refill. Similar to other dermal matrices, infection was a commonly encountered problem. However, BTM proved more tolerant to this and was able to be salvaged in most cases, allowing the second stage to proceed as normal.

Pervasive function and evidence for selection across standing genetic variation in S. cerevisiae.

Quantitative genetics aims to map genotype to phenotype, often with the goal of understanding how organisms evolved. However, it remains unclear whether the genetic variants identified are exemplary of evolution. Here we analyzed progeny of two wild Saccharomyces cerevisiae isolates to identify 195 loci underlying complex metabolic traits, resolving 107 to single polymorphisms with diverse molecular mechanisms. More than 20% of causal variants exhibited patterns of emergence inconsistent with neutrality. Moreover, contrary to drift-centric expectation, variation in diverse wild yeast isolates broadly exhibited this property: over 30% of shared natural variants exhibited phylogenetic signatures suggesting that they are not neutral. This pattern is likely attributable to both homoplasy and balancing selection on ancestral polymorphism. Variants that emerged repeatedly were more likely to have done so in isolates from the same ecological niche. Our results underscore the power of super-resolution mapping of ecologically relevant traits in understanding adaptation and evolution.

Mapping Causal Variants with Single-Nucleotide Resolution Reveals Biochemical Drivers of Phenotypic Change.

Understanding the sequence determinants that give rise to diversity among individuals and species is the central challenge of genetics. However, despite ever greater numbers of sequenced genomes, most genome-wide association studies cannot distinguish causal variants from linked passenger mutations spanning many genes. We report that this inherent challenge can be overcome in model organisms. By pushing the advantages of inbred crossing to its practical limit in Saccharomyces cerevisiae, we improved the statistical resolution of linkage analysis to single nucleotides. This "super-resolution" approach allowed us to map 370 causal variants across 26 quantitative traits. Missense, synonymous, and cis-regulatory mutations collectively gave rise to phenotypic diversity, providing mechanistic insight into the basis of evolutionary divergence. Our data also systematically unmasked complex genetic architectures, revealing that multiple closely linked driver mutations frequently act on the same quantitative trait. Single-nucleotide mapping thus complements traditional deletion and overexpression screening paradigms and opens new frontiers in quantitative genetics.

Comprehensive and quantitative mapping of RNA-protein interactions across a transcribed eukaryotic genome.

RNA-binding proteins (RBPs) control the fate of nearly every transcript in a cell. However, no existing approach for studying these posttranscriptional gene regulators combines transcriptome-wide throughput and biophysical precision. Here, we describe an assay that accomplishes this. Using commonly available hardware, we built a customizable, open-source platform that leverages the inherent throughput of Illumina technology for direct biophysical measurements. We used the platform to quantitatively measure the binding affinity of the prototypical RBP Vts1 for every transcript in the Saccharomyces cerevisiae genome. The scale and precision of these measurements revealed many previously unknown features of this well-studied RBP. Our transcribed genome array (TGA) assayed both rare and abundant transcripts with equivalent proficiency, revealing hundreds of low-abundance targets missed by previous approaches. These targets regulated diverse biological processes including nutrient sensing and the DNA damage response, and implicated Vts1 in de novo gene "birth." TGA provided single-nucleotide resolution for each binding site and delineated a highly specific sequence and structure motif for Vts1 binding. Changes in transcript levels in vts1Δ cells established the regulatory function of these binding sites. The impact of Vts1 on transcript abundance was largely independent of where it bound within an mRNA, challenging prevailing assumptions about how this RBP drives RNA degradation. TGA thus enables a quantitative description of the relationship between variant RNA structures, affinity, and in vivo phenotype on a transcriptome-wide scale. We anticipate that TGA will provide similarly comprehensive and quantitative insights into the function of virtually any RBP.

Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits.

Prions are a paradigm-shifting mechanism of inheritance in which phenotypes are encoded by self-templating protein conformations rather than nucleic acids. Here, we examine the breadth of protein-based inheritance across the yeast proteome by assessing the ability of nearly every open reading frame (ORF; ∼5,300 ORFs) to induce heritable traits. Transient overexpression of nearly 50 proteins created traits that remained heritable long after their expression returned to normal. These traits were beneficial, had prion-like patterns of inheritance, were common in wild yeasts, and could be transmitted to naive cells with protein alone. Most inducing proteins were not known prions and did not form amyloid. Instead, they are highly enriched in nucleic acid binding proteins with large intrinsically disordered domains that have been widely conserved across evolution. Thus, our data establish a common type of protein-based inheritance through which intrinsically disordered proteins can drive the emergence of new traits and adaptive opportunities.

The Burns Registry of Australia and New Zealand: progressing the evidence base for burn care.

OBJECTIVE: Analysis of data from the Burns Registry of Australia and New Zealand (BRANZ) to determine the extent of variation between participating units in treatment and in specific outcomes during the first 4 years of its operation. DESIGN: BRANZ, an initiative of the Australian and New Zealand Burn Association, is a clinical quality registry developed in accordance with the Australian Commission on Safety and Quality in Healthcare national operating principles. SETTING: Patients with burn injury who fulfil pre-defined criteria are transferred to and managed in designated burn units. There are 17 adult and paediatric units in Australia and New Zealand that manage almost all patients with significant burn injury. Twelve of these units treat adult patients. PARTICIPANTS: Data on 7184 adult cases were contributed by ten acute adult burn units to the registry between July 2010 and June 2014.Major outcomes: In-hospital mortality, hospital length of stay, skin grafting rates, and rates of admission to intensive care units. RESULTS: Considerable variations in unit profiles (including numbers of patients treated), in treatment and in outcomes were identified. CONCLUSIONS: Despite the highly centralised delivery of care to patients with severe or complex burn injury, and the relatively small number of specialist burn units, we found significant variation between units in clinical management and in outcomes. BRANZ data from its first 4 years of operation support its feasibility and the value of further development of the registry. Based on these results, the focus of ongoing research is to improve understanding of the reasons for variations in practice and of their effect on outcomes for patients, and to develop evidence-informed clinical guidelines for burn management in Australia and New Zealand.

A Randomized Controlled Study of Silver-Based Burns Dressing in a Pediatric Emergency Department.

Silver-impregnated dressings are increasingly preferred over silver sulfadiazine cream in the management of pediatric burns. An ideal burns dressing would provide a moist, sterile environment, discourage infection, and not require painful dressing changes. This study sought to determine whether silver sodium carboxymethyl cellulose (Aquacel Ag, ConvaTec, Greensboro, NC) dressing is a superior treatment to nanocrystalline silver-coated polyethylene (Acticoat, Smith & Nephew, London, United Kingdom) dressing in pediatric patients with partial thickness burns. The authors conducted a single-blind, randomized controlled trial in 89 patients presenting to Starship Children's Emergency Department with uncomplicated partial-thickness burns. Patients were randomized to receive either an Acticoat (n = 45) or Aquacel Ag (n = 44) dressing. Photographs of the burn before dressing and at day 10 were assessed by two blinded pediatric burn surgeons to determine the primary outcome and percentage epithelialization. Secondary outcomes were number of dressing changes required and number and type of adverse events. Both treatment groups achieved satisfactory rates of burn healing. There was no difference between groups in the percentage epithelialization at day 10 (Acticoat [mean ± SD] = 93 ± 14%; Aquacel Ag = 94 ± 17%, P = .89). Adverse events such as infection and escalation of care were rare, with no difference detected between groups. Compared with Acticoat, Aquacel Ag dressings required significantly less dressing changes per patient {Acticoat [median (interquartile range)] = 2 (2-2), Aquacel Ag=1 (1-1), P = .03}. Both Acticoat and Aquacel Ag dressings are effective burn dressings, allowing reepithelialization and preventing infection in a subset of uncomplicated partial-thickness burns in pediatric patients. Aquacel Ag requires fewer dressing changes. This decrease in frequency of dressing changes and direct manipulation of the wound, which can be distressing or require additional intervention, identified Aquacel Ag as the superior dressing. The majority of partial thickness pediatric burns heal within 10 days; however, a considerable minority requires the wound to be dressed for a longer period of time and/or specialist intervention. To identify these patients, expert review of the wound at 10 days postburn is recommended.

Posttranslational control of Cdc25 degradation terminates Drosophila's early cell-cycle program.

In most metazoans, early embryonic development is characterized by rapid mitotic divisions that are controlled by maternal mRNAs and proteins that accumulate during oogenesis. These rapid divisions pause at the midblastula transition (MBT), coinciding with a dramatic increase in gene transcription and the degradation of a subset of maternal mRNAs. In Drosophila, the cell-cycle pause is controlled by inhibitory phosphorylation of Cdk1, which in turn is driven by downregulation of the activating Cdc25 phosphatases. Here, we show that the two Drosophila Cdc25 homologs, String and Twine, differ in their dynamics and that, contrary to current models, their downregulations are not controlled by mRNA degradation but through different posttranslational mechanisms. The degradation rate of String protein gradually increases during the late syncytial cycles in a manner dependent on the nuclear-to-cytoplasmic ratio and on the DNA replication checkpoints. Twine, on the other hand, is targeted for degradation at the onset of the MBT through a switch-like mechanism controlled, like String, by the nuclear-to-cytoplasmic ratio, but not requiring the DNA replication checkpoints. We demonstrate that posttranslational control of Twine degradation ensures that the proper number of mitoses precede the MBT.

Development of an extemporaneous oral liquid formulation of oxandrolone and its stability evaluation.

Many references exist in the literature identifying the usefulness of oxandrolone in treating muscle wasting due to various conditions including severe burns. However, there is an absence of dosage form alternatives as it is only available as tablets. The dose for children is weight based (0.1 mg/kg) which is difficult to achieve with the currently available tablets of 2.5 mg and 10 mg. The literature provides ample evidence of clinical importance but little guidance on extemporaneous oral liquid formulation of oxandrolone. In order to develop and validate an extemporaneous liquid formulation, suspensions of oxandrolone were developed using locally available (New Zealand) vehicles. Combinations of these vehicles with ethanol, as advised in some articles were also tried. Assay method was developed for oxandrolone using High Performance Liquid Chromatography (HPLC) and Mass Spectroscopy (LC-MS). The formulations were evaluated for stability as per the International Conference on Harmonization (ICH) stability guidelines. They were observed for physical and chemical stability at different time points over a period of 28 days. A stable and validated liquid formulation of oxandrolone has been developed which can be made under the hospital and community pharmacy conditions. The formula utilises commercially available oxandrolone tablets, crushed and dispersed in Simple Syrup BP or Orablend(®) vehicle. The formulation has confirmed stability for 21 days and can be easily made with locally available vehicles.

Total care requirements of burn patients: implications for a disaster management plan.

The purpose of this study was to determine the operative and ward-based requirements of burn patients as a first step in the development of a National Health Emergency Multiple Complex Burn Action Plan. A retrospective review of 1043 patients admitted to the National Burn Centre at Middlemore Hospital, Auckland, New Zealand, from June 2006 to June 2009 was undertaken. Outcome measures included the number of operative procedures, operative time, length of inpatient stay, nursing hours, and allied health hours. A mean of 0.3 operating theater visits and 22.8 minutes of operating time was needed per percentage total body surface area (TBSA) burn. Length of inpatient stay equated to 1.1 days per percentage TBSA burn. There was an exponential relationship between operative requirements and burn surface area. Total operating theater time could be predicted from a formula based on burn surface area, mean depth, and type of burn. Operative time required was greatest in the first week and roughly halved each week after this, whereas nursing and allied health hours remained relatively constant. On the basis of operative requirements in the first week, patients with acute burn injuries totaling up to 129% TBSA could be treated at one time at the authors' institution. This study provides an objective trigger point for the activation of a disaster plan and enables us to predict operative and staffing requirements on a week by week basis, taking into account the existing workload. This information can be used to plan both the acute and protracted phase of a national response to a burn disaster.