A US perspective on closing the carbon cycle to defossilize difficult-to-electrify segments of our economy.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

Primary retropharyngeal leiomyosarcoma in a young cat.

Case summary: An Oriental Shorthair cat, aged 1 year and 6 months, developed progressive stridor and a palpable right ventral cervical mass. Fine-needle aspiration of the mass was inconclusive, while thoracic radiography and CT showed no evidence of metastasis. There was initial improvement in stridor with oral doxycycline and prednisolone treatment, but it recurred 4 weeks later and excisional biopsy was performed. Histopathology with immunohistochemistry diagnosed leiomyosarcoma with incomplete surgical margins. Adjunctive radiation therapy was declined. Repeated physical examination and CT 7 months postoperatively documented no evidence of mass recurrence. Relevance and novel information: This is the first reported case of retropharyngeal leiomyosarcoma in a young cat with no evidence of local reoccurrence 7 months following an excisional biopsy.

Non-injection-site soft tissue sarcoma in cats: outcome following adjuvant radiotherapy.

OBJECTIVES: Biological behaviour and treatment options of non-injection-site soft tissue sarcomas (nFISS) in cats are less well understood than in dogs. The aim of this retrospective study was to assess the outcomes of cats with nFISS following treatment with adjuvant radiotherapy. METHODS: The medical records of cats with soft tissue sarcomas in locations not associated with, and histology reports not suggestive of, injection-site sarcomas were reviewed. All cats underwent adjuvant radiotherapy, either hypofractionated (32-36 Gy delivered in weekly 8-9 Gy fractions) or conventionally fractionated (48-54 Gy delivered in 16-18 3 Gy fractions) to microscopic disease. RESULTS: In total, 18 cats were included in the study, 17 with extremity nFISS and one with facial nFISS. Nine received radiotherapy after a single surgery and nine after multiple surgeries for recurrent nFISS. Eight cats were treated with a hypofractionated protocol and 10 with a conventionally fractionated protocol. The median follow-up time was 540 days (range 51-3317 days). The tumour recurred in eight (44.4%) cats following adjuvant radiotherapy; it recurred in three (37.5%) cats following a hypofractionated protocol and in five (50%) cats following a conventionally fractionated protocol. The overall median progression-free interval (PFI) for 17/18 cats was 2748 days, while the median PFI for the 7/8 cats with recurrence was 164 days. The recurrence for one cat was reported, but the date was unknown and it was therefore censored from these data. When stratifying based on the protocol, the median PFI for hypofractionated and conventionally fractionated protocols was 164 days and 2748 days, respectively. Statistically, there was no significant difference between the two protocols (P = 0.636). CONCLUSIONS AND RELEVANCE: Adjuvant radiotherapy resulted in good long-term tumour control in 12/18 cats with nFISS. Further studies in larger populations are required to assess the significance of radiation dose and fractionation on tumour control and the effect of multiple surgeries prior to initiation of radiotherapy on outcome.

Use of a cyclical hypofractionated radiotherapy regime ('QUAD shot') for the treatment of feline sinonasal carcinomas.

OBJECTIVES: Radiation therapy is the treatment of choice for cats with sinonasal carcinomas. Different protocols have been described in the literature, though a clear consensus regarding the optimal protocol is lacking. The aim of the study was to describe the tolerability, efficacy and outcome of cats treated with a cyclical hypofractionated protocol. METHODS: Cats with histologically diagnosed sinonasal carcinomas in a single institution were retrospectively included. All patients were treated with a cyclical hypofractionated protocol ('QUAD shot' regime). Cats were treated with 4 Gray (Gy) delivered in four fractions within 48 h, with a minimum of 6 h between two treatments, and repeated every 3-4 weeks for a total dose of 48 Gy in three cycles. RESULTS: Seven cats met the inclusion criteria. Nasal discharge and sneezing were the most common presenting complaints. All cats presented with advanced stage of disease with CT examination (three with modified Adams stage 3 and four with stage 4). Clinical improvement was seen in six cats. Five cats had a follow-up CT; one had a complete response, two had partial responses, one had stable disease and one had progressive disease. Two cats were still alive at the time of writing while four were euthanased owing to tumour-related causes. The median overall survival time was 460 days. The 1-year survival time was 80% and the 2-year survival time was 0%. Severe acute or late toxicity was not reported. CONCLUSIONS AND RELEVANCE: This is the first report of a cyclical hypofractionated protocol in the veterinary literature that can provide prolonged survival in cats with advanced stage sinonasal carcinoma. Its use should be considered in patients when prolonged hospitalisation can be detrimental to quality of life, while still delivering a therapeutic total dose of radiation therapy.

The role of toceranib phosphate in dogs with non-mast cell neoplasia: A systematic review.

The use of tyrosine kinase inhibitors (TKI) has gained significant importance in veterinary cancer patients over the last decade. Toceranib phosphate has been licensed for the treatment of dogs with mast cell tumours. Its molecular similarity to sunitinib, a TKI used in human medicine, has led many veterinary oncologists to use this agent for multiple neoplastic diseases. The aim of the current study was to perform a systematic review of the evidence for the use of toceranib in dogs with non-mast cell neoplasia. Two electronic databases were searched. Publications were included if toceranib was used as a treatment option in canine patients. Studies and case reports were excluded if toceranib was used as part of a multi-modal treatment plan and response or outcome data related to toceranib therapy were not described. A total of 28 studies were included from 122 references. The most common types of neoplasias identified were neuroendocrine tumours, anal gland sac adenocarcinoma, and osteosarcoma. Multiple other neoplasias had one or two studies identified to describe the use of toceranib. Results of the study support that toceranib phosphate may have efficacy against certain types of neoplasia under certain conditions, such as neuroendocrine tumours, gastrointestinal stromal tumours and anal sac adenocarcinomas, while it is probably not effective for the management of metastatic osteosarcoma based on the findings of the review.

Lomustine, methotrexate and cytarabine chemotherapy as a rescue treatment for feline lymphoma.

OBJECTIVES: The aim of this study was to assess the efficacy and tolerability of lomustine, methotrexate and cytarabine chemotherapy as rescue treatment for feline lymphoma. METHODS: The medical records of 13 cats treated with lomustine, methotrexate and cytarabine for relapsed high-grade feline lymphoma, at a single institution between 2013 and 2018, were examined. All anatomical types were included. Data were analysed using descriptive statistics. RESULTS: Nine cats received all three drugs and four cats received only two drugs owing to progressive disease. In cats that received (or in which there was intention to treat with) all three drugs, 6/13 (46%) demonstrated a complete or partial response to chemotherapy. Treatment was generally well tolerated, although two cats experienced Veterinary Comparative Oncology Group (VCOG) grade 3 neutropenia and one cat experienced VCOG grade 3 thrombocytopenia. The median progression-free survival was 61 days (range 16-721 days). CONCLUSIONS AND RELEVANCE: CHOP-(cyclophosphamide, doxorubicin, vincristine, prednisolone) and COP-based protocols are established first-line chemotherapy for feline lymphoma, but standard rescue protocols are lacking. Lomustine has become a popular single-agent option, but prolonged or cumulative myelosuppression can result in treatment delays, risking relapse. Therefore, a multidrug lomustine-based protocol may be advantageous, and, from first principles, should also better overcome resistance. This study suggests that lomustine, methotrexate and cytarabine may represent an efficacious and well-tolerated protocol for feline lymphoma rescue.

Investigation of thyroid function in dogs treated with the tyrosine kinase inhibitor toceranib.

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty-four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow-up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop-out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.

Retrospective comparison of first-line adjuvant anthracycline vs metronomic-based chemotherapy protocols in the treatment of stage I and II canine splenic haemangiosarcoma.

Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first-line adjuvant anthracycline (AC) or metronomic (MC)-based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC- or MC-based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety-three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47-3352) and the overall median TTP was 185 days (range 37-1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47-3352 days), 338 days for the AMC group (range 79-1623 days) and 225 days for the MC group (range 57-911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings.

Evaluation of a multi-agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non-Hodgkin high-grade lymphomas: a single centre's experience.

The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.

External beam radiotherapy for the treatment of feline salivary gland carcinoma: six new cases and a review of the literature.

CASE SERIES SUMMARY: Salivary gland carcinoma is uncommon in cats. We report the outcome of radiation therapy in six cases (four salivary gland adenocarcinomas, one tubulopapillary adenocarcinoma, one carcinoma). Five were treated after surgical excision of the primary tumour, but four had gross disease (primary or metastatic) at the time of starting radiotherapy. Exact progression-free interval from the start of radiotherapy in the two cats where this was known was 120 and 144 days, respectively. One cat was signed off at 766 days with no evidence of recurrence. Another cat was in remission at 202 days (when last seen by the referring practice) but subsequently developed recurrence (date uncertain). Survival time was known for three cats (55 days, 258 days and 570 days from initiation of radiotherapy, respectively). In two cases, locoregional progressive disease (PD) was confirmed, and the other presumed as the cause of death. Two cats, known to have developed PD, were alive at the time of writing (at 206 and 549 days, respectively). No cat died as a result of distant metastatic disease. RELEVANCE AND NOVEL INFORMATION: There is a paucity of information on the treatment of salivary gland tumours. In humans, as in cats, there is no optimised standard of care for malignant tumours. It is accepted that, for surgical candidates (even with large tumours), surgery and radiotherapy is superior to radiotherapy alone. However, the benefits of postoperative radiotherapy compared with surgery alone are only clear in patients with high-risk tumours (ie, those with large and invasive primary tumours, close or incomplete margins, high histopathological grade, histological evidence of neural or vascular invasion, or positive lymph nodes). This population is analogous to the population reported here, and likely to most cats presented in practice. Thus, radiation therapy may help improve locoregional control and survival in cats.

Do Serum Creatinine Levels Show Clinically Significant Fluctuations on Serial Determinations on the Siemens Advia 1800 Analyzer?

BACKGROUND: The goal of this work was to determine whether there are clinically significant fluctuations in the level of serum creatinine on serial determinations, especially in the borderline range (1.1-1.3 mg/dl), after specimen storage. METHODS: Sixty-one serum samples were analyzed. They were divided into three categories based on the initial serum creatinine measurement: low (≤1.0 mg/dl), borderline (1.1-1.3 mg/dl), and high (≥1.4 mg/dl). The specimens were stored at 4°C and run on the Siemens Advia 1800 chemistry analyzer on days 1, 3, and 11. RESULTS: Statistical comparisons of the three groups were made using the unpaired t-test, yielding a two-tailed P-value for each group comparison. The P-values ranged from 0.0829 to 0.3892, indicating no statistically significant difference between the standard deviations of each group. CONCLUSIONS: Mild-to-moderate fluctuations in precision occur in successive serum creatinine determinations. The overwhelming majority of these fluctuations should not affect clinical decision making.

Toxicity and response in cats with neoplasia treated with toceranib phosphate.

Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity limited to mild gastrointestinal or myelosuppressive effects in the majority of cases (10/14) in this study; however, hepatotoxicity is a concern. Response to treatment in this small cohort was similar to that reported in dogs.

Metastatic Small Cell Carcinoma of the Lung: An Unusual Cause of Acute Fulminant Hepatic Failure.

For patients with acute fulminant liver failure, imaging and histopathologic studies are indicated to reveal the underlying etiology, and metastatic small cell carcinoma should be included in the clinical differential diagnosis when appropriate.

Reproducibility of Serum Potassium Values in Serum From Blood Samples Stored for Increasing Times Prior to Centrifugation and Analysis.

GOALS: The goal of this work was to determine if immediate versus postponed centrifugation of samples affects the levels of serum potassium. METHODS: Twenty participants donated normal venous blood that was collected in four serum separator tubes per donor, each of which was analyzed at 0, 1, 2, or 4 hr on the Siemens Advia 1800 autoanalyzer. RESULTS: Coefficients of variation (CVs) for potassium levels ranged from 0% to 7.6% with a mean of 3 ± 2%. ANOVA testing of the means for all 20 samples showed a P-value of 0.72 (>0.05) indicating that there was no statistically significant difference between the means of the samples at the four time points. Sixteen samples were found to have CVs that were ≤5%. Two samples showed increases of potassium from the reference range to levels higher than the upper reference limit, one of which had a 4-hr value that was within the reference or normal range (3.5-5 mEq/l). Overall, most samples were found to have reproducible levels of serum potassium. CONCLUSIONS: Serum potassium levels from stored whole blood collected in serum separator tubes are, for the most part, stable at room temperature for at least 4 hr prior to analysis. However, some samples can exhibit significant fluctuations of values.

Tetracyanoethylene oxide- functionalized graphene and graphite characterized by Raman and Auger spectroscopy.

The tetracyanoethylene oxide (TCNEO) functionalization of chemical vapor deposition grown large area graphene and graphite was performed using reaction of TCNEO with carbon surface in chlorobenzene. The successful functionalization has been confirmed by Raman and Auger spectroscopy, and by numerical modeling of the structure and vibrational modes of TCNEO-functionalized graphene. Raman spectra of TCNEO-functionalized graphene and graphite show several groups of lines corresponding to vibrations of attached carbonyl ylide. One of key signatures of TCNEO attachment is the high intensity Raman band at ~1450 cm-1, which represents the C-C=C in plane vibrations in functionalization-distorted graphene. Raman spectra indicate the existence of central (pristine) attachment of TCNEO to graphene surface.