From resilience thinking to Resilience Planning: Lessons from practice.

Resilience thinking has frequently been proposed as an alternative to conventional natural resource management, but there are few studies of its applications in real-world settings. To address this gap, we synthesized experiences from practitioners that have applied a resilience thinking approach to strategic planning, called Resilience Planning, in regional natural resource management organizations in Australia. This case represents one of the most extensive and long-term applications of resilience thinking in the world today. We conducted semi-structured interviews with Resilience Planning practitioners from nine organizations and reviewed strategic planning documents to investigate: 1) the key contributions of the approach to their existing strategic planning, and 2) what enabled and hindered the practitioners in applying and embedding the new approach in their organizations. Our results reveal that Resilience Planning contributed to developing a social-ecological systems perspective, more adaptive and collaborative approaches to planning, and that it clarified management goals of desirable resource conditions. Applying Resilience Planning required translating resilience thinking to practice in each unique circumstance, while simultaneously creating support among staff, and engaging external actors. Embedding Resilience Planning within organizations implied starting and maintaining longer-term change processes that required sustained multi-level organizational support. We conclude by identifying four lessons for successfully applying and embedding resilience practice in an organization: 1) to connect internal "entrepreneurs" to "interpreters" and "networkers" who work across organizations, 2) to assess the opportunity context for resilience practice, 3) to ensure that resilience practice is a learning process that engages internal and external actors, and 4) to develop reflective strategies for managing complexity and uncertainty.

High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Weekly-dose doxorubicin (WDA) in advanced breast cancer.

Doxorubicin in a weekly fixed dose of 20 mg as i.v. bolus (WDA) was given to 48 patients with mostly pretreated progressing breast cancer. The response rate (CR + PR) was 9/48 (19%), and a further 16 (33%) of the patients achieved stable disease. Myelosuppression was mild and without clinical significance. Other side effects, particularly nausea, vomiting and hair loss were also relatively mild. Cardiac toxicity, however, was seen in six patients. Five of these six patients were previously treated with mitoxantrone or combination chemotherapy containing doxorubicin. Median response duration was 10+ months for responders and 11+ months in patients who had stable disease. It is concluded that weekly-dose doxorubicin has a favourable profile with a low frequency of side effects and that this treatment is an alternative to other cancer chemotherapy in breast cancer, especially when not only CR and PR but even stabilization of disease is considered of benefit to the patient.

The dynamics of social-ecological systems in urban landscapes: Stockholm and the National Urban Park, Sweden.

This study addresses social-ecological dynamics in the greater metropolitan area of Stockholm County, Sweden, with special focus on the National Urban Park (NUP). It is part of the Millennium Ecosystem Assessment (MA) and has the following specific objectives: (1) to provide scientific information on biodiversity patterns, ecosystem dynamics, and ecosystem services generated; (2) to map interplay between actors and institutions involved in management of ecosystem services; and (3) to identify strategies for strengthening social-ecological resilience. The green areas in Stockholm County deliver numerous ecosystem services, for example, air filtration, regulation of microclimate, noise reduction, surface water drainage, recreational and cultural values, nutrient retention, and pollination and seed dispersal. Recreation is among the most important services and NUP, for example, has more than 15 million visitors per year. More than 65 organizations representing 175,000 members are involved in management of ecosystem services. However, because of population increase and urban growth during the last three decades, the region displays a quite dramatic loss of green areas and biodiversity. An important future focus is how management may reduce increasing isolation of urban green areas and enhance connectivity. Comanagement should be considered where locally managed green space may function as buffer zones and for management of weak links that connect larger green areas; for example, there are three such areas around NUP identified. Preliminary results indicate that areas of informal management represent centers on which to base adaptive comanagement, with the potential to strengthen biodiversity management and resilience in the landscape.

A weekly schedule of low-dose doxorubicin in treatment of advanced breast cancer.

A phase II study of weekly low-dose doxorubicin (6 to 12 mg/m2) showed it to be an effective, well-tolerated therapy in advanced breast cancer. Although most of the 34 patients studied had been clinically resistant to previous endocrine measures and/or other kinds of chemotherapy, had a median score of 60 on Karnofsky's index, and had predominantly visceral metastases, an objective response was obtained in 20 of 34 patients (four complete remissions, 16 partial remissions) for a median duration of 12+ months. Ten patients experienced no change in their condition for three to 12 months (median, six months). Eight of the 17 patients who had myelosuppression at the beginning of the study had an objective response lasting 4+ to 27+ months (median, 11 months). Eleven of the patients had previously received 500 or more mg/m2 of doxorubicin and were retreated with additional doses of doxorubicin (median cumulative dose, 800 mg/m2) without any clinical signs of toxicity.

Immune functions in melanoma patients during treatment with interferon [HuIFN-alpha (Le)] alone or in combination with cimetidine.

While leukocyte interferon was found therapeutically ineffective in a series of 20 patients with metastatic malignant melanoma, subsequent combination treatment with interferon and cimetidine induced 5 complete and 1 partial tumour remissions. Prior to interferon therapy initiation, regressor patients demonstrated a significantly greater ability to mediate antibody-dependent cellular cytotoxicity than progressor patients and also tended to have higher natural killer-cell activity. These differences were more pronounced following in vitro exposure of effector cells to interferon alone or in combination with cimetidine. During therapy the differences decreased to statistically nonsignificant levels. The number of immunoglobulin producing cells and lymphocyte proliferative responses to Con A were found to increase in both patient groups after interferon therapy initiation; but this augmentation vanished gradually upon combined treatment with cimetidine. A gradual decrease of the number of T lymphocytes and granulocytes was also recorded. None of the demonstrated alterations in the activities of circulating lymphocytes appears to be a relevant correlate to the efficacy of combined therapy compared to interferon alone.

Influence of a fatty acid on duodenal motility.

The duodenal transport mechanism has been studied by a method combining roentgen-fluorography and multiple pressure recordings. Three main types of motility were distinguished: propulsive, retrograde, and static. The motor pattern in the first part of the duodenum was studied in 15 individuals under basal condition and after application in the duodenal lumen of sodium myristate. The resulting inhibition of gastric emptying was found to be correlated to a significant inhibition of the propulsive movements in the duodenum. The two others types of motor activity did not change significantly.

Duodenal motility pattern in duodenal ulcer disease.

The motility in the first part of the duodenum has been studied by a method combining roentgen fluorography and multiple pressure recordings in 7 normal volunteers, in 7 patients having gastric, and in 7 having duodenal, ulcer. A significantly lower number of retrograde motor sequences was found in cases with duodenal ulcer than in normals, while patients with gastric ulcers showed no such difference. This abnormality in subjects with duodenal ulcer was interpreted as a deficiency in the transport of neutralized duodenal contents from more distal parts of the duodenum up into the bulb. The abnormality can explain the earlier known lower pH in the duodenal bulb in subjects with duodenal ulcer and contribute to the pathogenesis of the disease.

Intraperitoneal drain in cholelithiasis operations.

571 patients were operated on for cholelithiasis, 70 acute cases and 501 chronic ones. On 142 cases of the latter type choledochus exploration was performed, while on the others only simple cholecystectomy was carried out. Intraperitoneal drain in the form of a latex tube was used on all the acute cases except 4, on all who underwent choledochus exploration except 3, and on 254 of the 359 chronic cases on whom simple cholecystectomy was performed. The analysi of the material shows that the indications for intraperitoneal drainage are not very convincing after cholecystectomy at a chronic stage, considering the amount of fluid drawn via the intraperitoneal drain and the complications that arose. After choledochus exploration, however, intraperitoneal drain serves its purpose in connection with the removal of the choledochus drain. Intraperitoneal drain should therefore be used when choledochus has been explored. In routine cases it should not be removed until the choledochus drain has been withdrawn.

Mitoxantrone as a first-line treatment of advanced breast cancer.

Forty-two women with measurable or evaluable advanced breast cancer who had received neither prior chemotherapy for advanced disease nor any anthracycline-containing regimen as adjuvant were entered in a phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione). Patients were aged from 36 to 80 years, performance status was from 0 to 2. All patients had normal hematological status and normal renal and liver function tests. Cardiac scintigraphy and sonography techniques were used to monitor cardiac function. Mitoxantrone was administered at a dose of 14 mg/m2 in 100 ml 5% dextrose solution over 30 minutes, repeated every three weeks. The number of courses per patient ranged from 2 to 12. Of 42 eligible patients 39 were fully evaluable for response and all for drug toxicity. Responses to treatment were: complete response four patients, partial response 10 patients, stable disease 18 patients and progressive disease seven patients. The overall response rate was 36% (95% confidence limits 20-52%). Three patients showed decreased left ventricular ejection fraction but no patient developed signs of overt left ventricular failure during the treatment period. Hematological and gastrointestinal toxicities were mild. Hair loss was minimal. The data indicate that mitoxantrone is an effective agent for the treatment of advanced breast cancer with mild side-effects, especially with respect to nausea/vomiting, hair loss and cardiotoxicity.

Mastectomy only versus radical mastectomy and postoperative radiotherapy in node negative, resectable breast cancer. A randomized trial.

Patients with clinically node negative resectable breast cancer were randomized to either mastectomy only or radical mastectomy and radiotherapy, and followed for 15-20 years. During follow-up axillary metastases occurred with the same frequency after mastectomy as was initially observed in the group that underwent axillary dissection. There was no significant survival difference between the two groups. When adjusting the treatment effect for differences in age, tumour size, lymph node metastases, and histology, the outcome after radical mastectomy plus irradiation was significantly inferior. Comedo carcinoma proved also in this study to carry a poor prognosis.

Phase II clinical study of toremifene in patients with metastatic breast cancer. Preliminary communication.

Twelve postmenopausal women with inoperable or metastatic breast cancer were given toremifene at a daily dose of 60 mg. The patients had no prior endocrine or cytotoxic therapy and further inclusion criteria were bidimensionally measurable disease, performance status above 50, expected survival of more than 3 months and estrogen receptor status positive or undetermined. Objective response [complete remission (CR) + partial remission (PR)] was achieved in 6 patients (50%) and stable disease was obtained in 5 patients. No side effects of the treatment were noted.

Phase II clinical study of high-dose toremifene in patients with advanced breast cancer.

Thirteen postmenopausal women with advanced local or metastatic breast cancer were treated with the antiestrogen toremifene at a daily dose of 200 mg. All patients had failed previous treatment with different types of endocrine therapy and/or cytotoxic drugs. Objective response was only seen in one patient. Treatment was usually well tolerated but in three cases the drug had to be withdrawn due to side effects.

The protective effect of intra-arterial vasopressin injections on the small bowel during fractionated abdominal irradiation. A study in pigs.

The radioprotective effect of vasopressin-induced intestinal ischemia was investigated in pigs. A bolus injection in the cranial mesenteric artery, of a vasopressin solution, 0.05 IU/kg body weight, was followed by irradiation of the small intestine with 6 MV roentgen rays. Three different fraction schedules were used. Weight changes in the animals and the histologic appearance of their intestines were recorded two weeks after irradiation and compared with the findings in untreated animals. Intra-arterial vasopressin was very effective in protecting the intestine. Vasopressin treatment given before 2 fractions with relatively high radiation doses in a 6-fraction regimen was so effective that it may form the basis of a treatment model applicable in man.

Radioprotective effect of local administration of lysine-vasopressin and triglycyl-lysine-vasopressin on the rectal mucosa in rats.

Reactions from the rectal mucosa often give rise to troublesome side-effects during and after radiotherapy in the pelvic region. Local vasoconstriction in the rectal mucosa will cause an ischemia which will decrease the sensitivity of the mucosal cells to radiation and thereby these side-effects can be reduced. Triglycyl-lysine-vasopressin applied rectally in 1% Blanose solution gave in the present study significant radioprotection of the rectal mucosa in the doses of 0.8, 1.6, and 3.2 mg. These doses are, however, very high. Triglycyl-lysine-vasopressin in 1.2% Natrosol solution in a dose of 128 micrograms did not show any certain protective effects. However lysine-vasopressin in 1.2% Natrosol solution in a dose of 16 micrograms gave significant radioprotection of the rectal mucosa. This dose level has in a previous study not given any significant effects on the systemic circulation. Lysine-vasopressin in Natrosol solution seems to be a suitable combination for further studies.

Metastatic malignant melanoma: regression induced by combined treatment with interferon [HuIFN-alpha(Le)] and cimetidine.

With the aim of potentiating the anti-tumour effect of interferon in metastatic malignant melanoma by concomitant inhibition of suppressor T cells, oral cimetidine (histamine-2 receptor antagonist) medication was added to interferon (HuIFN-alpha(Le] therapy in a series of 20 patients. While no objective tumour responses were recorded with interferon treatment alone administered intramuscularly or intratumorally, six patients had objective tumour regressions on subsequent combined therapy. Five out of eight patients with metastases confined to skin and subcutaneous tissue had complete tumour regressions while one patient with skin and lung metastases achieved an extensive partial regression of the skin tumour and a complete roentgenological regression of the lung metastasis. Three additional patients attained a stable disease status for prolonged periods of time. Histopathological examinations confirmed disappearance and/or degeneration of melanoma cells and demonstrated a marked lymphocyte infiltration in tumour sites of the patients with objective tumour regression.

A randomized study of chemotherapy with procarbazine, vincristine, and lomustine with and without radiation therapy for astrocytoma grades 3 and/or 4.

The authors undertook a controlled, prospective, randomized study of 171 patients with supratentorial astrocytoma grades 3 and/or 4 (classified according to Kernohan). All patients were given chemotherapy consisting of procarbazine, vincristine, and lomustine (CCNU) (PVC). Half of the patients received whole-brain irradiation (RT) to a dose of 5800 cGy in the tumor-bearing hemisphere and 5000 cGy in the contralateral hemisphere. After diagnosis of progressive tumor growth, patients received individual treatment. The endpoint of the study was time to progression, but cases were followed until the patients died. Median time to progression (MTP) for the whole randomized population was 21 weeks. Median survival time (MST) was 53 weeks; 18% of patients survived for 2 years or longer. Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP (81 weeks) and MST (124 weeks) than all other patients. For patients less than 50 years of age treated with PVC alone, MTP was 21 weeks and MST was 66 weeks. For patients more than 50 years of age treated with PVC plus RT, MTP was 23 weeks and MST was 51 weeks; in the PVC group, MTP was 17 weeks and MST was 39 weeks. Age, Karnofsky index, areas of Grade 2, and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses. Patients less than 50 years of age treated with PVC plus RT had significantly longer survival (P = 0.037) when correcting for these factors in a multi-variate analysis.