Salps off Baja California (BC) showed substantial changes during El Niño of 1997-1998 and La Niña of 1998-1999. Salps were particularly abundant during the warm phase and showed a decreasing trend after the transition to cool conditions (October 1998). Salp swarms (>1 salp m -3) were present throughout the study period, with the exception of October 1999 and October 2000. They appeared more frequently S of Punta Baja (30°N). The most abundant species was Thalia orientalis followed by Salpa fusiformis. T. orientalis decreased in abundance from winter 1998 to autumn 1999, while S. fusiformis showed a strong increase during the development and establishment of La Niña (autumn 1998 and winter 1999). Other species (T. rhomboides, T. cicar, Cyclosalpa strongylenteron, C. polae, S. cylindrica and Ritteriella amboinensis) associated with warmer waters were present off the southernmost part of the BC peninsula. They were probably advected into the area from the SSW by an intensified coastal poleward jet that characterized the El Niño peak in the area. Estimates of carbon ingestion from daily rations of Thalia spp. and S. fusiformis indicated that swarms required from <1 to >100% of the daily primary production and phytoplankton biomass. Fecal pellet production of swarms of these species was estimated at between <1 and 609 mg C m-2 d-1. Considering that size and sinking rates of fecal pellets are related to salp body size, the swarms of Thalia and S. fusiformis may have had a differential impact on the pelagic ecosystem in terms of recycling and vertical transport of biogenic material through the water column. © Inter-Research 2006.

This report summarizes physical and biological conditions in the California Current System (CCS), from Oregon to Baja California, in 2001 and 2002. The principal sources of the observations described here are the CalCOFI (California Cooperative Oceanic Fisheries Investigations), IMECOCAL (Investigaciones Mexicanas de la Corriente de California), and U.S. GLOBECLTOP (Global Ecosystems Long-term Observation Program) programs. Large-scale atmospheric and oceanic conditions in the Pacific point to a fourth consecutive La Niña-like year. This has contributed to generally stronger than normal upwelling and uncharacteristically cool waters in much of the CCS, a pattern that has persisted since late 1998. Biological productivity has been generally higher as well, particularly off Oregon. Within the observed interannual fluctuations of recent years, these conditions suggest a generally elevated production off California and Oregon, but cool conditions have led to lower than normal zooplankton biomass off Baja California. Although the tropical Pacific has exhibited some indications of a developing El Niño, it is not likely to impact the CCS during the productive upwelling season of 2002. These observations are continuing evidence that a regime shift may have occurred in 1998, resulting in substantial change in ecosystem structure in the CCS. Continued monitoring and analysis of the state of the CCS in this context is needed. We outline a plan for an integrated monitoring program for the entire region, through the creation of ACCEO (Alliance for California Current Ecosystem Observation).

Background

In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years.

Patients and methods

Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.

Results

Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.

Conclusions

Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.

Clinical trial registration

NCT01345682 (ClinicalTrials.gov).

The Belle II detector will provide a major step forward in precision heavy flavor physics, quarkonium and exotic states, searches for dark sectors, and many other areas. The sensitivity to a large number of key observables can be improved by about an order of magnitude compared to the current measurements, and up to two orders in very clean search measurements. This increase in statistical precision arises not only due to the increased luminosity, but also from improved detector efficiency and precision for many channels. Many of the most interesting observables tend to have very small theoretical uncertainties that will therefore not limit the physics reach. This book has presented many new ideas for measurements, both to elucidate the nature of current anomalies seen in flavor, and to search for new phenomena in a plethora of observables that will become accessible with the Belle II dataset. The simulation used for the studiesinthis book was state ofthe artat the time, though weare learning a lot more about the experiment during the commissioning period. The detector is in operation, and working spectacularly well.