The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Whimsical (Waldenstrom's Macroglobulinemia Study Involving CArt-wheeL): A Global Patient-Derived Data Registry Capturing Treatment, Quality of Life and COVID-19 Data

Introduction: Patient-derived data can increase breadth of knowledge in rare cancers like Waldenström's Macroglobulinemia (WM), including patient-reported outcomes (PROs). WhiMSICAL (Waldenström's Macroglobulinemia Study Involving CArt-wheeL) is the only global registry capturing patient-derived data for hypothesis generation in WM. Rapidly adaptable, it has been amended to capture Coronavirus Disease 2019 (COVID-19) data. Methods: An ethically-approved WM-specific extension to www.cart-wheel.org, an online rare cancer database for patient-derived data, was developed by clinician and patient investigators. Participants complete consent, and enter symptom, pathology, treatment and PRO (EORTC-QLQ-C30, Impact of Event Scale-6) data online. Recruitment strategies utilizing social media tools are driven by the International Waldenström's Macroglobulinemia Foundation investigators. A validation study compared patient-entered data with data-manager-entered data in the Australia & New Zealand Lymphoma & Related Diseases Registry (LaRDR). To capture the impact of COVID-19, additional questions on COVID-19 testing, symptoms and therapy, as well as effect on WM management in those without COVID-19, were included in April 2020. Results: 453 patients from 19 countries have been recruited, predominantly from USA (46%) and Australia (25%), with male predominance (62%). At diagnosis, median age was 61 (range 24-83), median IgM 2620 mg/dL (IQR 1320-3850 mg/dL, n=175) and median hemoglobin 11.4 g/dL (IQR 9.5-12.9 g/dL, n=181). Of the 365 (81%) patients providing symptoms at diagnosis, fatigue/muscle weakness was most common (46%) and 30% were asymptomatic. Using the Impact of Event Scale for symptoms of post-traumatic stress disorder (PTSD) resulting from a cancer diagnosis, the mean score among 387 patients was 5.9 (no stress=0, maximal stress=24), with 39/387 (10%) scoring >13 (PPV 94% for PTSD, Thoresen et al, 2010). This proportion did not increase for scores entered after March 1st, 2020 - 12/123 (10%) - when the COVID-19 pandemic became a global crisis. Marked treatment variation was noted, with 47 different first-line therapeutic combinations documented by 302 patients. Median time from diagnosis to first treatment for USA patients was 48 days (IQR 13-404, n=133) vs Rest of World (ROW) 176 days (IQR 20-885, n=163), (p=0.01). At median follow up of 38.5 months, first-line bendamustine rituximab had superior time to next treatment outcomes compared to other first-line therapies: rituximab monotherapy, dexamethasone-rituximab-cyclophosphamide and Bruton tyrosine kinase inhibitors (BTKi, Figure 1). 51 patients exposed to BTKi had a trend to higher EORTC QLQ-C30 global scales, mean 78.6±17.7, compared to 148 not exposed: mean 73.4±22.6 (p=0.13), despite higher treatment burden: median lines of treatment 2 (IQR 1-4) and 1 (IQR 1-2), respectively (p83%. 188/453 (42%) participants responded to the impact of COVID-19 questions; 75/188 (40%) had reduced face-to-face reviews, 4/188 (2%) had delays to starting treatment and 57/188 (30%) documented no impact. Of the 188 respondents, 23 (12%) had COVID-19 testing, with two returning a positive result and neither requiring hospitalization. Conclusion: WhiMSICAL is a robust, rapidly adaptable, global patient-derived data platform, providing insight into patient symptoms, real-world therapies and PROs. It is a scientific, ethically-approved portal for contributing the patients' voice in this rare lymphoma

Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia

Waldenström macroglobulinaemia is an indolent B-cell lymphoma with clearly defined criteria for diagnosis, initiation of therapy, and response, which was established by consensus panels at previous International Workshops for Waldenström Macroglobulinaemia (IWWM). The treatment options for Waldenström macroglobulinaemia continued to be researched after the publication of the eighth IWWM consensus recommendations in 2016, and at the tenth IWWM in New York, USA (October, 2018) an international consensus panel was formed to update treatment recommendations. Participants were selected as members of the consensus panel based on their expertise on Waldenström macroglobulinaemia. The initial live discussion took place during the tenth IWWM meeting and two separate teleconferences were held in June, 2019, and January, 2020, to refine recommendations. No external or financial support was received for the elaboration of these recommendations. According to these updated consensus recommendations, alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients with Waldenström macroglobulinaemia. In previously treated patients with Waldenström macroglobulinaemia who had an initial durable response, reuse of a previous regimen or another primary therapy regimen are acceptable options. Novel BTK inhibitors (acalabrutinib, zanubrutinib, tirabrutinib) and the BCL2 antagonist venetoclax appear safe and active, and represent emerging options for the treatment of Waldenström macroglobulinaemia. The choice of therapy should be guided by the patient's clinical profile, genomic features, and drug availability

Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma

BACKGROUND Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P=0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs