Ocean currents and herbivory drive macroalgae-to-coral community shift under climate warming.

Coral and macroalgal communities are threatened by global stressors. However, recently reported community shifts from temperate macroalgae to tropical corals offer conservation potential for corals at the expense of macroalgae under climate warming. Although such community shifts are expanding geographically, our understanding of the driving processes is still limited. Here, we reconstruct long-term climate-driven range shifts in 45 species of macroalgae, corals, and herbivorous fishes from over 60 years of records (mainly 1950-2015), stretching across 3,000 km of the Japanese archipelago from tropical to subarctic zones. Based on a revised coastal version of climate velocity trajectories, we found that prediction models combining the effects of climate and ocean currents consistently explained observed community shifts significantly better than those relying on climate alone. Corals and herbivorous fishes performed better at exploiting opportunities offered by this interaction. The contrasting range dynamics for these taxa suggest that ocean warming is promoting macroalgal-to-coral shifts both directly by increased competition from the expansion of tropical corals into the contracting temperate macroalgae, and indirectly via deforestation by the expansion of tropical herbivorous fish. Beyond individual species' effects, our results provide evidence on the important role that the interaction between climate warming and external forces conditioning the dispersal of organisms, such as ocean currents, can have in shaping community-level responses, with concomitant changes to ecosystem structure and functioning. Furthermore, we found that community shifts from macroalgae to corals might accelerate with future climate warming, highlighting the complexity of managing these evolving communities under future climate change.

[How Jungian Psychology Has Been Developed in Japan].

Jungian Psychology was introduced to Japan in 1931 by Kokyo Nakamura for the first time in Sekai Daishiso Zenshu ("The Complete Works of Thoughts in the World") vol. 33. (Shunjusha Publishing Company). Yoshitaka Takahashi and others made Jungian Psychology more accessible to the Japanese public in the mid-1950s although they did not succeed in full repre- sentation of the fundamental ideas of C. G. Jung. It was Hayao Kawai who truly understood those ideas and initiated the Jungian movements in Japan in 1967. In my opinion, however, there are hardly any Jungian Analysts who develop Jung's ideas further enough to reach a new awareness of the human psyche except a very few people such as Neumann, E., and Gug- genbtihl-Craig, A., Kalff, D. M., Spiegelman, M., Meier, C. A. and Hillman, J., Giegerich, W, in the West and H. Kawai and me in Japan. Kawai develops and deepens Jungian thoughts to a cer- tain extent in his book, The Buddhist Priest Myoe : A Life of Dreams (Shohakusha Publishing Company), while his understanding of Buddhism does not exceed what D. T. Suzuki describes in his work, An Introduction to Zen Buddhism. That is to say the ideas of both Zen and Shin Buddhism are abstracted and assimilated in general Buddhism in his work, resulting in losing their unique features which could have been pursued further. Moreover, although Kawai translates Jung's idea of SynchronizitAt to "kyoji-sei" (synchronicity), I claim that "engi-ritsu" (the pratitya-samutpada principle) would be a more appropriate term to reflect the original concept as it would imply the opposite principle to"inga-ritsu" (the causal principle). It should be noted that the pratitya-samutpada principle is different from the Buddhist concept of pratitya- samutpada which includes causality. In addition I transcribed the Avatamsaka sutra, which originated in India and was developed in China. I also attended to the 2"d international confer- ence featuring the Avatamsaka sutra at Belesbat on the outskirts of Paris. Eventually I have reached an idea that when combined with the concept of the pratitya-samutpada principle, the Avatamsaka sutra could be considered as a-product of Eastern wisdom which would provide an insight beyond Jung. What was originally comprehended by Gautama Buddha was crystallised in abstract images of Amitabha and Vairocana in China during the second and fourth centuries. Amitabha is a celestial buddha that Shinran, the founder of Shin Buddhism, established his own understanding of in his school whereas Vairocana is a celestial buddha that appears in the Avatamsaka sutra. Vairocana could be taken as an image of the"rising sun", the creator of all things, while Amitabha as the "sinking sun", the saviour of all creatures. This picture of psychological cosmology gives a new perspective on the human psyche that would succeed Jungian Psychology. I believe this unique conception is equivalent to the findings in modern physical cosmology, such as Einstein's theories and the Alpha-Beta-Gamow paper, which provided a new understanding of the universe.

Intermediate- to long-term results after hybrid total hip arthroplasty in patients with rheumatoid arthritis.

There have been few reports describing intermediate- to long-term results after hybrid total hip arthroplasty in patients with rheumatoid arthritis. We followed up 52 hips in 44 patients aged 5 men and 39 women, with a mean of 11.5 years (range, 5-23.5 years). Revisions had been performed in 6 hips in 6 patients: 1 both acetabular and femoral components for infection, 1 acetabular component for aseptic loosening, 3 acetabular components for recurrent dislocation, and 1 acetabular component for dislodgement of the polyethylene liner from the metal shell. None of other acetabular or femoral components were revised or found to be loose at the final follow-up. Although postoperative dislocation remains a concern, hybrid total hip arthroplasty had an acceptable result in patients with rheumatoid arthritis.

[An autopsy case of unresectable colon cancer who developed lung injury by cetuximab].

We report the case of a woman in her 60s with unresectable advanced colon cancer. After the first course of cetuximab as second-line therapy, she had developed drug-induced lung injury. Steroid pulse therapy had been ineffective, and she died of respiratory failure on day 9. The pathological examination of autopsy lung specimens revealed diffuse alveolar damage(DAD). Details of the cetuximab-induced lung injury are unclear. However, in 3 previous reports of lung injury by cetuximab, the postmortem findings were similar to this case. We concluded that DAD seems to be one of the pathological features of lung injury caused by cetuximab.

Polyubiquitination events mediate polymethylmethacrylate (PMMA) particle activation of NF-kappaB pathway.

The pathologic response to implant wear-debris constitutes a major component of inflammatory osteolysis and remains under intense investigation. Polymethylmethacrylate (PMMA) particles, which are released during implant wear and loosening, constitute a major culprit by virtue of inducing inflammatory and osteolytic responses by macrophages and osteoclasts, respectively. Recent work by several groups has identified important cellular entities and secreted factors that contribute to inflammatory osteolysis. In previous work, we have shown that PMMA particles contribute to inflammatory osteolysis through stimulation of major pathways in monocytes/macrophages, primarily NF-κB and MAP kinases. The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKKγ/NEMO. We have shown recently that interfering with the NF-κB and MAPK activation pathways, through introduction of inhibitors and decoy molecules, impedes PMMA-induced inflammation and osteolysis in mouse models of experimental calvarial osteolysis and inflammatory arthritis. In this study, we report that PMMA particles activate the upstream transforming growth factor ß-activated kinase-1 (TAK1), which is a key regulator of signal transduction cascades leading to activation of NF-κB and AP-1 factors. More importantly, we found that PMMA particles induce TAK1 binding to NEMO and UBC13. In addition, we show that PMMA particles induce TRAF6 and UBC13 binding to NEMO and that lack of TRAF6 significantly attenuates NEMO ubiquitination. Altogether, these observations suggest that PMMA particles induce ubiquitination of NEMO, an event likely mediated by TRAF6, TAK1, and UBC13. Our findings provide important information for better understanding of the mechanisms underlying PMMA particle-induced inflammatory responses.

[A complete response of scirrhous gastric carcinoma treated with trastuzumab combination therapy].

Trastuzumab is the first molecular-target medicine for gastric cancer in acknowledgment of the effectiveness and safety in a randomized controlled trial for the HER2-positive gastric cancer. The HER2-positive rate of gastric cancer tends to be high for a well-differentiated adenocarcinoma. We report a case of HER2-positive scirrhous gastric carcinoma we treated, for whom a complete response was obtained by trastuzumab combination therapy. He was a 62-year-old man. In April, 2006, he was diagnosed with metastatic scirrhous gastric carcinoma(mainly poorly-differentiated adenocarcinoma). We become clear with HER2 strong positive in a pathology tissue and started capecitabine+cisplatin+trastuzumab therapy. We confirmed the disappearance of the lesion at the 10th cycle and judged it to be a complete response. The HER2 of advanced gastric cancer must be screened immediately without asking patients for their background or their clinical and pathologic features.

[Modified FOLFOX6(mFOLFOX6)in metastatic colorectal carcinoma patients with poor performance status].

Because mFOLFOX6 has few contraindications, it is useful for poor performance status(PS)cases. However, in Japan, there are some reports that the dose is reduced easily. We retrospectively examined the safety/usefulness of the full dose mFOLFOX6(first-line)for advanced colon cancer patients with poor PS. Four of five cases had improved PS. The response rate was 60%. Grade 3/4 adverse events were infection, leukopenia, and neutropenia. Treatment-related deaths within 60 days of starting treatment were absent. Full-dose mFOLFOX6 for poor PS may be beneficial. However, we must consider the increased risk of adverse events.

Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms.

Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously.

Retrospective analysis of the international standard-dose FOLFIRI (plus bevacizumab) regimen in Japanese patients with unresectable advanced or recurrent colorectal carcinoma.

BACKGROUND: When applying the topoisomerase inhibitor irinotecan (CPT) with the infusional fluorouracil/levofolinate (FOLFIRI) ± bevacizumab chemotherapy regimen in cases of advanced colorectal carcinoma, the international standard dose for CPT is 180 mg/m(2). Despite this, 150 mg/m(2) CPT is widely prescribed and is the maximum dosage covered by Japanese health insurance. Consequently, the safety of dosing at the international standard has not been tested comprehensively and the efficacy of FOLFIRI in Japan may be underestimated. METHODS: To evaluate the safety of FOLFIRI (+bevacizumab) in clinical practice using international standards, we reviewed medical records of 53 patients who received FOLFIRI (+bevacizumab) with CPT 180 mg/m(2) as first-line treatment between September 2004 and August 2009. The primary endpoint of the study was to measure the relative dose intensity (RDI) of CPT after four courses. The secondary endpoint was to assess treatment completion rate, adverse events, response rate, progression-free survival (PFS) and overall survival (OS) among all patients. RESULTS: The RDI and the treatment completion rate were 88.9% and 69.8%, respectively, in the 53 patients. Accompanying grade 3 or 4 adverse events included neutropenia (35.8%), febrile neutropenia (7.5%), and diarrhea (3.8%). Supportive care managed all toxicity symptoms. Median durations for PFS and OS were 10.3 and 26.5 months, respectively. CONCLUSION: FOLFIRI (+bevacizumab) with the international standard dose of CPT is feasible in clinical practice. In order to minimize deviation of the Japanese regimen from global best practice, international dose standards should be followed.

Cemented calcar replacement femoral component in revision hybrid total hip arthroplasty.

We evaluated intermediate-term to long-term survival of cemented calcar replacement femoral components in hybrid revision total hip arthroplasty. We followed up 52 hips in 50 patients for a mean of 11.4 years. Six (12%) femoral components had been revised: 2 for aseptic loosening, 2 for periprosthetic fracture, and 2 for deep infection. One additional femoral component was definitely loose. The number of previous revision operations (P = .004), preoperatively poorer femoral bone stock (P = .005), and postoperative poor cement mantle grading (P = .003) were significant factors for failure. Kaplan-Meier analysis revealed that the 15-year survival rate was 90% with mechanical failure as the end point. This technique remains a reasonable option for the first-time revision, especially for older and less active patients.

Hybrid total hip arthroplasty using specifically-designed stems for patients with developmental dysplasia of the hip. A minimum five-year follow-up study.

A 4-U hybrid total hip arthroplasty (THA) system was specifically designed for patients with developmental dysplasia of the hip (DDH). Straight stem with an appropriate offset and various size variations are advantages. We followed 128 hips in 124 patients, 13 men and 111 women, for a mean of 6.5 years (range, 5.0-7.5 years). Two acetabular and femoral components in two patients had been revised for infection, one acetabular component had been revised for recurrent dislocation, and one femoral component had been revised for periprosthetic femoral fracture. None of the acetabular or femoral components were revised for loosening or were found to be loose at follow-up. The Harris hip score increased from a preoperative average of 42 points to 88 points at the most recent follow-up. Primary THA using the 4-U system had a good mid-term result in patients with DDH. This system could be applied for all patients including those with the narrowest and deformed femurs.

[A case of metastatic colon cancer in which repetition of standard treatment proved effective].

In palliative chemotherapy, a focus on palliative treatment is recommended in cases that are unresponsive to multiple drugs. Careful judgment is needed, however, because when treatment is inadequate, cases that are considered to be unresponsive may include some in which chemotherapy would be effective. We treated a patient with metastatic colon cancer who was judged to be unresponsive to multiple drugs at another hospital, yet repetition of standard therapy proved effective. We report this case as an instructive example of the importance of maintaining dose intensity. The patient was a 60-year-old man. Lung metastasis appeared after he had undergone proctectomy and received adjuvant chemotherapy by his previous doctor. Low-dose intensity IFL therapy, FOLFOX4 therapy (once a month), and FOLFIRI therapy (once only) had been performed, but the patient's condition worsened and he was referred to our hospital. This case could not be considered unresponsive to multiple drugs because the treatment had been insufficient, and so we restarted FOLFIRI treatment with the international standard dose and obtained control of the disease. Treatment was then continued, and the patient died 2 years and 11 months after he was first examined at our hospital. Simple palliative treatment alone should not be given unthinkingly when patients are referred for outpatient palliative care. Full consideration of the dosing and schedule is needed.

[A case report of conversion therapy for initially unresectable colorectal cancer liver metastases after cetuximab as third-line treatment].

The introduction of monoclonal antibodies into the treatment protocols for metastatic colorectal cancer(mCRC)has significantly improved outcomes. There are some patients with mCRC, initially judged unresectable, who become resectable after chemotherapy. For patients with isolated liver metastases, surgical resection is recommended when feasible. We experienced a case in which an initially unresectable mCRC liver metastases converted into a resectable one after cetuximab monotherapy as third-line treatment. The sample from hepatectomy was a pathologically complete response; no remnants were detected. The management of liver metastases contributes to improvements in the clinical setting. For conducting a multimodal treatment of mCRC, the participation of various specialists such as medical oncologists, colorectal/hepaticsurgeons and diagnostic/therapeutic radiologists is indispensable. Furthermore, it is necessary to construct an evidence-based consensus on potentially resectable CRC liver metastases in each hospital.

Porous-coated cementless acetabular components without bulk bone graft in revision surgery.

We previously reported the average 9.3-year (range, 5-13 years) results of 74 patients (83 hips) with porous-coated acetabular components that were placed without bulk bone graft at revision surgery. Since the previous report, 7 patients (7 hips) died before the minimum follow-up of 10 years, and 1 patient (1 hip) was lost to follow-up. We now report the average 15.6-year (range, 10-20 years) results for 66 patients (75 hips). Three additional acetabular components were removed or revised again: 2 for infection and 1 for dislodgement of the polyethylene liner from the metal shell. Overall, 7 (7%) components required removal or repeat revision. No shell was revised for aseptic loosening, and none was categorized as loose during the entire follow-up period.

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Inhibition of IKK activation, through sequestering NEMO, blocks PMMA-induced osteoclastogenesis and calvarial inflammatory osteolysis.

Osteoclasts, the primary bone-resorbing cells, play a crucial role in periprosthetic bone loss in response to implant-derived wear debris. Differentiation and activation of osteoclasts at the implant-bone interface are fueled by elevated levels of locally secreted inflammatory cytokines that heighten the osteolytic response. Among these cytokines are members of the TNF superfamily, including TNF and RANKL, which primarily act through activation of the transcription factor NF-kappaB. Activation of NF-kappaB is required for osteoclast formation, and its inhibition hampers osteoclastogenesis and bone loss. Activation of NF-kappaB is permitted following its dissociation from the inhibitory protein IkappaBalpha, an event subsequent to phosphorylation of the latter protein by the upstream IkappaBalpha kinase (IKK) complex. Our recent findings show that attenuating IKK complex assembly, by using a short peptide termed NEMO-binding domain (NBD) peptide, that blocks binding of IKK2 and IKK1 to IKKgamma/NEMO, inhibits NF-kappaB activation, and arrests RANKL-induced osteoclastogenesis. In this study, we examined if NBD is capable of blocking inflammatory osteolysis by PMMA particles. Our findings indicate that NBD peptide inhibits PMMA-induced IKK2 and NF-kappaB activation. More importantly, this peptide potently arrests PMMA-stimulated osteoclastogenesis and alleviates PMMA-induced inflammatory and osteolytic responses in mice. Thus, NBD peptide is considered as a promising modality to regulate inflammatory osteolysis.

Incidence of Venous Thromboembolism in Patients Undergoing Major Hip Surgeries at a Single Institution: A Prospective Study.

BACKGROUND: Venous thoromboembolism (VTE) is one of the most significant complications after hip surgeries. Many studies have been reported about the incidence of VTE after THA, but a small number of reports were found concerning Periacetabular osteotomy, Revision THA and Surgery for hip fracture postoperatively. Furthermore, there exists no comparative study of the incidence of VTE among major hip surgeries at a single institution. We reported the incidence of VTE among hip surgeries performed at a single institution. METHODS: A total of 820 Hip surgeries were performed at same institution. The procedures included 420 hips that underwent primary total hip arthroplasties (THA), 91 revision or removal of total hip arthroplasties (Revision THA), 144 periacetabular osteotomy (PAO) and 165 surgery for hip fracture (SHF) between 2006 and 2012. VTE was detected by Multidetector computed tomography (MDCT) that scanned 768 cases and by ultrasound that scanned 52cases postoperative 10-14 days. RESULTS: The overall incidence of VTE was 12.2% (100 of 820). The incidence of VTE after THA was 13.1% (55 of 420), Revision THA was 13.2% (12 of 91), PAO was 2.1% (3 of 144) and SHF was 18.1% (30 of 165). The incidence of VTE was significantly higher in SHF than in PAO. CONCLUSION: This data indicates that the incidence of VTE after PAO is significantly lower than SHF and relatively lower than THA and Revision THA. A younger age and non-invasion of the bone marrow of the femur may have affected the result. Prophylaxis therapy was effective especially on SHF.

Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study).

Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100-180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41-76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1-39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100-120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be clinically insignificant. Routine use of skin toxicity prevention is currently under evaluation.

Projecting the impacts of rising seawater temperatures on the distribution of seaweeds around Japan under multiple climate change scenarios.

Seaweed beds play a key role in providing essential habitats and energy to coastal areas, with enhancements in productivity and biodiversity and benefits to human societies. However, the spatial extent of seaweed beds around Japan has decreased due to coastal reclamation, water quality changes, rising water temperatures, and heavy grazing by herbivores. Using monthly mean sea surface temperature (SST) data from 1960 to 2099 and SST-based indices, we quantitatively evaluated the effects of warming seawater on the spatial extent of suitable versus unsuitable habitats for temperate seaweed Ecklonia cava, which is predominantly found in southern Japanese waters. SST data were generated using the most recent multiple climate projection models and emission scenarios (the Representative Concentration Pathways or RCPs) used in the Coupled Model Intercomparison Project phase 5 (CMIP5). In addition, grazing by Siganus fuscescens, an herbivorous fish, was evaluated under the four RCP simulations. Our results suggest that continued warming may drive a poleward shift in the distribution of E. cava, with large differences depending on the climate scenario. For the lowest emission scenario (RCP2.6), most existing E. cava populations would not be impacted by seawater warming directly but would be adversely affected by intensified year-round grazing. For the highest emission scenario (RCP8.5), previously suitable habitats throughout coastal Japan would become untenable for E. cava by the 2090s, due to both high-temperature stress and intensified grazing. Our projections highlight the importance of not only mitigating regional warming due to climate change, but also protecting E. cava from herbivores to conserve suitable habitats on the Japanese coast.

Adaptation pathways of global wheat production: Importance of strategic adaptation to climate change.

Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations.