Evidence for the earliest structural use of wood at least 476,000 years ago.

Wood artefacts rarely survive from the Early Stone Age since they require exceptional conditions for preservation; consequently, we have limited information about when and how hominins used this basic raw material1. We report here on the earliest evidence for structural use of wood in the archaeological record. Waterlogged deposits at the archaeological site of Kalambo Falls, Zambia, dated by luminescence to at least 476 ± 23 kyr ago (ka), preserved two interlocking logs joined transversely by an intentionally cut notch. This construction has no known parallels in the African or Eurasian Palaeolithic. The earliest known wood artefact is a fragment of polished plank from the Acheulean site of Gesher Benot Ya'aqov, Israel, more than 780 ka (refs. 2,3). Wooden tools for foraging and hunting appear 400 ka in Europe4-8, China9 and possibly Africa10. At Kalambo we also recovered four wood tools from 390 ka to 324 ka, including a wedge, digging stick, cut log and notched branch. The finds show an unexpected early diversity of forms and the capacity to shape tree trunks into large combined structures. These new data not only extend the age range of woodworking in Africa but expand our understanding of the technical cognition of early hominins11, forcing re-examination of the use of trees in the history of technology12,13.

Community engagement interventions for communicable disease control in low- and lower- middle-income countries: evidence from a review of systematic reviews.

BACKGROUND: Community engagement (CE) interventions include a range of approaches to involve communities in the improvement of their health and wellbeing. Working with communities defined by location or some other shared interest, these interventions may be important in assisting equity and reach of communicable disease control (CDC) in low and lower-middle income countries (LLMIC). We conducted an umbrella review to identify approaches to CE in communicable disease control, effectiveness of these approaches, mechanisms and factors influencing success. METHODS: We included systematic reviews that: i) focussed on CE interventions; ii) involved adult community members; iii) included outcomes relevant to communicable diseases in LLMIC; iv) were written in English. Quantitative results were extracted and synthesised narratively. A qualitative synthesis process enabled identification of mechanisms of effect and influencing factors. We followed guidance from the Joanna Briggs Institute, assessed quality with the DARE tool and reported according to standard systematic review methodology. RESULTS: Thirteen systematic reviews of medium-to-high quality were identified between June and July 2017. Reviews covered the following outcomes: HIV and STIs (6); malaria (2); TB (1); child and maternal health (3) and mixed (1). Approaches included: CE through peer education and community health workers, community empowerment interventions and more general community participation or mobilisation. Techniques included sensitisation with the community and involvement in the identification of resources, intervention development and delivery. Evidence of effectiveness of CE on health outcomes was mixed and quality of primary studies variable. We found: i) significantly reduced neonatal mortality following women's participatory learning and action groups; ii) significant reductions in HIV and other STIs with empowerment and mobilisation interventions with marginalised groups; iii) significant reductions in malaria incidence or prevalence in a small number of primary studies; iv) significant reductions in infant diarrhoea following community health worker interventions. Mechanisms of impact commonly occurred through social and behavioural processes, particularly: changing social norms, increasing social cohesion and social capacity. Factors influencing effectiveness of CE interventions included extent of population coverage, shared leadership and community control over outcomes. CONCLUSION: Community engagement interventions may be effective in supporting CDC in LLMIC. Careful design of CE interventions appropriate to context, disease and community is vital.

The changing health priorities of earthquake response and implications for preparedness: a scoping review.

OBJECTIVES: Earthquakes have substantial impacts on mortality in low- and middle-income countries (LMIC). The academic evidence base to support Disaster Risk Reduction activities in LMIC settings is, however, limited. We sought to address this gap by identifying the health and healthcare impacts of earthquakes in LMICs and to identify the implications of these findings for future earthquake preparedness. STUDY DESIGN: Scoping review. METHODS: A scoping review was undertaken with systematic searches of indexed databases to identify relevant literature. Key study details, findings, recommendations or lessons learnt were extracted and analysed across individual earthquake events. Findings were categorised by time frame relative to earthquakes and linked to the disaster preparedness cycle, enabling a profile of health and healthcare impacts and implications for future preparedness to be established. RESULTS: Health services need to prepare for changing health priorities with a shift from initial treatment of earthquake-related injuries to more general health needs occurring within the first few weeks. Preparedness is required to address mental health and rehabilitation needs in the medium to longer term. Inequalities of the impact of earthquakes on health were noted in particular for women, children, the elderly, disabled and rural communities. The need to maintain access to essential services such as reproductive health and preventative health services were identified. Key preparedness actions include identification of appropriate leaders, planning and training of staff. Testing of plans was advocated within the literature with evidence that this is possible in LMIC settings. CONCLUSIONS: Whilst there are a range of health and healthcare impacts of earthquakes, common themes emerged in different settings and from different earthquake events. Preparedness of healthcare systems is essential and possible, in order to mitigate the adverse health impacts of earthquakes in LMIC settings. Preparedness is needed at the community, organisational and system levels.

The 2015 Nepal earthquake disaster: lessons learned one year on.

INTRODUCTION: The 2015 earthquake in Nepal killed over 8000 people, injured more than 21,000 and displaced a further 2 million. One year later, a national workshop was organized with various Nepali stakeholders involved in the response to the earthquake. The workshop provided participants an opportunity to reflect on their experiences and sought to learn lessons from the disaster. METHODS: One hundred and thirty-five participants took part and most had been directly involved in the earthquake response. They included representatives from the Ministry of Health, local and national government, the armed forces, non-governmental organizations, health practitioners, academics, and community representatives. Participants were divided into seven focus groups based around the following topics: water, sanitation and hygiene, hospital services, health and nutrition, education, shelter, policy and community. Facilitated group discussions were conducted in Nepalese and the key emerging themes are presented. RESULTS: Participants described a range of issues encountered, some specific to their area of expertize but also more general issues. These included logistics and supply chain challenges, leadership and coordination difficulties, impacts of the media as well as cultural beliefs on population behaviour post-disaster. Lessons identified included the need for community involvement at all stages of disaster response and preparedness, as well as the development of local leadership capabilities and community resilience. A 'disconnect' between disaster management policy and responses was observed, which may result in ineffective, poorly planned disaster response. CONCLUSION: Finding time and opportunity to reflect on and identify lessons from disaster response can be difficult but are fundamental to improving future disaster preparedness. The Nepal Earthquake National Workshop offered participants the space to do this. It garnered an overwhelming sense of wanting to do things better, of the need for a Nepal-centric approach and the need to learn the lessons of the past to improve disaster management for the future.

The health impact of the 2014-15 Ebola outbreak.

OBJECTIVES: The 2014-15 outbreak in West Africa was the largest and deadliest Ebola outbreak recorded; however, there remains uncertainty over its wider health consequences. Our objective was to provide a comprehensive overview of the impact of the Ebola outbreak on population health in the three most affected countries: Sierra Leone, Liberia and Guinea. STUDY DESIGN: Narrative review. METHODS: A narrative overview of the peer-reviewed and grey literature related to the impact and consequences of the Ebola outbreak was conducted, synthesizing the findings of literature retrieved from a structured search of biomedical databases, the Web and references of reviewed articles. RESULTS: The impact of the Ebola outbreak was profound and multifaceted. The health system was severely compromised due to overwhelming demand, healthcare workers deaths, resource diversion and closure of health facilities. Fear of Ebola and healthcare workers led to a breakdown in trust in health systems. Access to healthcare was compromised. Substantial reductions in healthcare utilization were reported including over 80% reductions in maternal delivery care in Ebola-affected areas, 40% national reductions in malaria admissions among children <5 years and substantial reductions in vaccination coverage. Socio-economic impacts included reduced community cohesion, education loss, reduced child protection, widespread job losses and food insecurity. Increased morbidity and mortality and reduced expected life expectancy were reported. CONCLUSIONS: This review highlights the scope and scale of the consequences of the Ebola outbreak on population health. Sustained commitment of the international community is required to support health system re-building and to urgently address unmet population health needs.

Intravesical chondroitin sulphate for interstitial cystitis/painful bladder syndrome.

INTRODUCTION: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the bladder. Bladder instillation is one avenue of treatment but evidence for its effectiveness is limited. Chondroitin sulphate solution 2.0% (Urocyst) is a glycosaminoglycan (GAG) replenishment therapy instilled for patients with IC/PBS. We assessed its effectiveness for treating IC/PBS in Northern Ireland. METHODS: Patients with IC/PBS were assessed with the O'Leary-Sant interstitial cystitis index score and global response assessment questionnaire prior to commencing treatment. Assessment with these questionnaires was performed after 6 treatments (10 weeks) and again after 10 treatments (24 weeks). Assessment end points were pain, urgency, symptom score and problem score. RESULTS: Data was collected on 10 patients, 9 female and 1 male. 6 patients had failed RIMSO-50 dimethyl sulphoxide (DMSO) 50% treatment prior. At baseline the mean pain score was 6.6, urgency score 7.00, symptom score 13.5 and problem score 12.5. After 24 weeks the mean pain score fell to 2.0, urgency score to 1.80, symptom score to 6.89 and problem score to 5.67. At 10 weeks the global response to treatment was 100%. Nocturia was the first symptom to improve with urgency and pain following. No side effects were noted during instillation and all patients tolerated the treatments. CONCLUSION: IC/PBS is a difficult disease to treat. It requires a multimodal approach. We found that intravesical chondroitin sulphate reduced pain, urgency and O'Leary-Sant symptom and problem scores in patients with IC/PBS. All patients tolerated the treatment and no side effects were reported.

Medical education and law: withholding/withdrawing treatment from adults without capacity.

BACKGROUND: Law is increasingly involved in clinical practice, particularly at the end of life, but undergraduate and postgraduate education in this area remains unsystematic. We hypothesised that attitudes to and knowledge of the law governing withholding/withdrawing life-sustaining treatment from adults without capacity (the WWLST law) would vary and demonstrate deficiencies among medical specialists. AIMS: We investigated perspectives, knowledge and training of medical specialists in the three largest (populations and medical workforces) Australian states, concerning the WWLST law. METHODS: Following expert legal review, specialist focus groups, pre-testing and piloting in each state, seven specialties involved with end-of-life care were surveyed, with a variety of statistical analyses applied to the responses. RESULTS: Respondents supported the need to know and follow the law. There were mixed views about its helpfulness in medical decision-making. Over half the respondents conceded poor knowledge of the law; this was mirrored by critical gaps in knowledge that varied by specialty. There were relatively low but increasing rates of education from the undergraduate to continuing professional development (CPD) stages. Mean knowledge score did not vary significantly according to undergraduate or immediate postgraduate training, but CPD training, particularly if recent, resulted in greater knowledge. Case-based workshops were the preferred CPD instruction method. CONCLUSIONS: Teaching of current and evolving law should be strengthened across all stages of medical education. This should improve understanding of the role of law, ameliorate ambivalence towards the law and contribute to more informed deliberation about end-of-life issues with patients and families.

Understanding the non-pharmacological correlates of self-reported efficacy of antidepressants.

OBJECTIVE: To explore the non-pharmacological correlates of the perceived effectiveness of antidepressants (ADs), thereby enhancing understanding of the mechanisms involved in recovery from depression while taking ADs. METHOD: An online survey was completed by 1781 New Zealand adults who had taken ADs in the previous 5 years. RESULTS: All 18 psychosocial variables measured were associated with depression reduction, and 16 with improved quality of life (QoL). Logistic regression models revealed that the quality of the relationship with the prescriber was related to both depression reduction and improved QoL. In addition, depression reduction was related to younger age, higher income, being fully informed about ADs by the prescriber, fewer social causal beliefs for depression and not having lost a loved one in the 2 months prior to prescription. Furthermore, both outcome measures were positively related to belief in 'chemical' rather than 'placebo' effects. CONCLUSION: There are multiple non-pharmacological processes involved in recovery while taking ADs. Enhancing them, for example focusing on the prescriber-patient relationship and giving more information, may enhance recovery rates, with or without ADs.

Medical practitioners' knowledge and self-reported practices of substitute decision making and implementation of advance care plans.

BACKGROUND: Advance care planning (ACP) provides patients with the ability to make their decisions known about how they would like to be treated if they lose capacity. Medical practitioners have a key role to play in providing information on ACP to their patients. This research explores their knowledge and attitudes to advance care planning and how this affects their practice. AIM: The objective of this study is to assess the NSW medical practitioners' knowledge and self-reported practice of ACP. METHODS: A postal survey of a random sample of 650 general practitioners plus 350 medical specialists from specialties most often involved in end-of-life decisions was conducted. Respondents' work location post codes were subsequently used to assign respondents to one of the eight NSW Area Health Services. The main outcome measures were medical practitioners' knowledge of and practice pertaining to ACP. RESULTS: Thirty-four per cent of specialists (n = 110) and 24% of general practitioners (n = 150) responded; the majority of respondents had heard of all ACP options. However, respondents' understanding of the uses and legal requirements of the relevant ACP options vary widely. CONCLUSIONS: Respect for patient wishes expressed in advance directives is reassuringly high. The findings suggest significant misunderstanding by medical practitioners of terminologies and systems around substitute decision-making for incompetent persons. Further education and standardisation of terminologies and systems across different jurisdictions would assist in addressing these issues. Low response rate, relating to only one legal jurisdiction, means results may not be generalisable.

Rack1 promotes epithelial cell-cell adhesion by regulating E-cadherin endocytosis.

E-cadherin and its cytoplasmic partners, catenins, mediate epithelial cell-cell adhesion. Disruption of this adhesion allows cancer cells to invade and metastasize. Aberrant activation of the Src tyrosine kinase disrupts cell-cell contacts through an E-cadherin/catenin-dependent mechanism. Previously we showed that Rack1 regulates the growth of colon cells by suppressing Src activity at G(1) and mitotic checkpoints, and in the intrinsic apoptotic and Akt cell survival pathways. Here we show that Rack1, partly by inhibiting Src, promotes cell-cell adhesion and reduces the invasive potential of colon cancer cells. Rack1 stabilizes E-cadherin and catenins at cell-cell contacts by inhibiting the Src phosphorylation of E-cadherin, the ubiquitination of E-cadherin by the E3 ligase Hakai and the endocytosis of E-cadherin. Upon depletion and restoration of extracellular calcium, Rack1 facilitates the re-assembly of E-cadherin-containing cell-cell contacts. Rack1 also blocks HGF-induced endocytosis of E-cadherin, disruption of cell-cell contacts and cell scatter. Our results uncover a novel function of Rack1 in maintaining the junctional homeostasis of intestinal epithelial cells by regulation of the Src- and growth factor-induced endocytosis of E-cadherin.

The housing and support needs of people with an intellectual disability into older age.

BACKGROUND: People with intellectual disabilities (IDs) are growing older as a population cohort. Many live at home with family members who are their carers but who are also becoming older and less able to provide care. The housing and support preferences of people with IDs and their carers into older age are poorly characterised in the literature. METHODS: Focus groups and individual interviews were conducted with 15 people with IDs who work in supported employment and with 10 family members who care for adults with IDs. Data were thematically analysed independently by two researchers. RESULTS: The major themes that emerged were as follows: (1) living arrangements; (2) housing preferences; (3) ageing in place; and (4) transition from informal to formal housing and support services. CONCLUSIONS: Participants with an ID and their carers want housing and support that enable people with an ID to maintain and enhance their social networks with their peers as they grow older and require transition to formal housing and support services, and to be able to 'age in place'. A preference was expressed for models of housing that provide the opportunity for people with an ID to live in close proximity to their peers and in large groups in the community rather than in small, dispersed community housing.

Performance of the Abbott RealTime CT/NG for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

A multicenter clinical study was conducted to evaluate the performance characteristics of the Abbott RealTime CT/NG assay, a multiplex real-time PCR assay, for simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The specimens were collected from a total of 3,832 male and female subjects at 16 geographically diverse sites. Specimens included male and female urine samples, male urethral swabs, female endocervical swabs, and self-collected and clinician-collected vaginal swabs. Specimens were tested with the automated Abbott RealTime CT/NG assay, Aptima Combo 2 assay (Gen-Probe), ProbeTec ET CT/GC assay (Becton Dickinson), and culture for N. gonorrhoeae. The Aptima Combo 2 assay, the ProbeTec assay, and the N. gonorrhoeae culture were used as the reference assays. For each subject, a patient infected status (PIS) was determined based on the combined results from the reference assays. The overall prevalence in female subjects was 8.9% for C. trachomatis and 3.8% for N. gonorrhoeae. The overall male prevalence was 18.2% for C. trachomatis and 16.7% for N. gonorrhoeae. The overall sensitivity and specificity of the Abbott RealTime CT/NG assay were 92.4% and 99.2% for C. trachomatis and 96.9% and 99.7% for N. gonorrhoeae, respectively. In comparison, the sensitivity and specificity, respectively, for the Aptima Combo 2 assay were 94.5% and 99.0% for C. trachomatis and 96.1% and 99.5% for N. gonorrhoeae, and those for the ProbeTec ET assay were 90.3% and 99.5% for C. trachomatis and 92.0% and 97.3% for N. gonorrhoeae in this study. The Abbott RealTime CT/NG assay offers C. trachomatis and N. gonorrhoeae dual detection with high sensitivity and specificity. The automated assay provides a useful alternative nucleic acid amplification assay for clinical laboratories and clinicians.

A novel pro-apoptotic function of RACK1: suppression of Src activity in the intrinsic and Akt pathways.

Earlier we showed that RACK1 regulates growth of human colon cells by suppressing Src activity at G(1) and mitotic checkpoints. Here, we show that RACK1 also induces apoptosis of the cells, partly by inhibiting Src. In the intrinsic pathway, RACK1 inhibits expression of anti-apoptotic Bcl-2 and Bcl-X(L), induces expression of pro-apoptotic Bim, targets Bim and Bax to the mitochondria, induces oligomerization of Bax (which requires Bim and inhibition of Src), depolarizes mitochondria membranes, releases cytochrome c, and activates caspases-9 and -3 and death substrates. Bax and Bim are required for RACK1-mediated mitochondrial cell death. RACK1-induced oligomerization of Bax is required for staurosporine-mediated cell death. RACK1 also induces apoptosis by blocking Src activation of the Akt cell survival pathway. This leads to activation of the transcription factor FOXO3, a potent inducer of apoptosis and G(1) arrest. Collectively, our results show that RACK1, partly by inhibiting Src, promotes mitochondrial cell death and blocks Akt-mediated cell survival. Thus, RACK1 inhibits growth and induces death of colon cells. Exploitation of these dual functions could lead to novel colon cancer therapies that mimic RACK1 function.

Influence of physicians' life stances on attitudes to end-of-life decisions and actual end-of-life decision-making in six countries.

AIM: To examine how physicians' life stances affect their attitudes to end-of-life decisions and their actual end-of-life decision-making. METHODS: Practising physicians from various specialties involved in the care of dying patients in Belgium, Denmark, The Netherlands, Sweden, Switzerland and Australia received structured questionnaires on end-of-life care, which included questions about their life stance. Response rates ranged from 53% in Australia to 68% in Denmark. General attitudes, intended behaviour with respect to two hypothetical patients, and actual behaviour were compared between all large life-stance groups in each country. RESULTS: Only small differences in life stance were found in all countries in general attitudes and intended and actual behaviour with regard to various end-of-life decisions. However, with regard to the administration of drugs explicitly intended to hasten the patient's death (PAD), physicians with specific religious affiliations had significantly less accepting attitudes, and less willingness to perform it, than non-religious physicians. They had also actually performed PAD less often. However, in most countries, both Catholics (up to 15.7% in The Netherlands) and Protestants (up to 20.4% in The Netherlands) reported ever having made such a decision. DISCUSSION: The results suggest that religious teachings influence to some extent end-of-life decision-making, but are certainly not blankly accepted by physicians, especially when dealing with real patients and circumstances. Physicians seem to embrace religious belief in a non-imperative way, allowing adaptation to particular situations.

Two steps forward, one step back: advance care planning, Australian regulatory frameworks and the Australian Medical Association.

The Australian Medical Association has recently adopted a policy position concerning advance care planning, which is generally supportive of extending patient self-determination beyond the loss of decision-making capacity. It calls for uniform national legislation for legally enforceable advance health directives (AHD), and statutory protection for practitioners who comply with valid AHD, or who do not comply on several grounds. Analysis of the grounds for non-compliance indicate that they undermine patient autonomy, and aspects of the policy are inconsistent with current common law and statutory regimes that allow an adult to complete a legally binding AHD. The policy therefore threatens the patient self-determination, which it endorses, and places doctors who participate in advance care planning at legal risk.

Characteristics of the m2000 automated sample preparation and multiplex real-time PCR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.

We evaluated a new real-time PCR-based prototype assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae developed by Abbott Molecular Inc. This assay is designed to be performed on an Abbott m2000 real-time instrument system, which consists of an m2000sp instrument for sample preparation and an m2000rt instrument for real-time PCR amplification and detection. The limit of detection of this prototype assay was determined to be 20 copies of target DNA for both C. trachomatis and N. gonorrhoeae, using serially diluted linearized plasmids. No cross-reactivity could be detected when 55 nongonococcal Neisseria isolates and 3 non-C. trachomatis Chlamydia isolates were tested at 1 million genome equivalents per reaction. Concordance with the Roche Amplicor, BDProbeTec ET, and Gen-Probe APTIMA Combo 2 tests was assessed using unlinked/deidentified surplus clinical specimens previously analyzed with these tests. For C. trachomatis, concordance for positive results ranged from 93.7% to 100%, while concordance for negative results ranged from 98.2% to 100%. For N. gonorrhoeae, concordance for positive and negative results ranged from 91.4% to 100% and 99.3% to 100%, respectively. A workflow analysis of the prototype assay was conducted to obtain information on throughput under laboratory conditions. At 48 samples/run, the time to first result for both C. trachomatis and N. gonorrhoeae was 4.5 h. A total of 135 patient specimens could be analyzed in 8.9 h, with 75 min of hands-on time. This study demonstrated the technical and clinical feasibility of the new Abbott real-time PCR C. trachomatis/N. gonorrhoeae assay.

RACK1 inhibits colonic cell growth by regulating Src activity at cell cycle checkpoints.

Previously, we showed that Src tyrosine kinases are activated early in the development of human colon cancer and are suppressed as intestinal cells differentiate. We identified RACK1 as an endogenous substrate, binding partner and inhibitor of Src. Here we show (by overexpressing RACK1, depleting Src or RACK1 and utilizing cell-permeable peptides that perturb RACK1's interaction with Src) that RACK1 regulates growth of colon cells by suppressing Src activity at G(1) and mitotic checkpoints, and consequently delaying cell cycle progression. Activated Src rescues RACK1-inhibited growth of HT-29 cells. Conversely, inhibiting Src abolishes growth promoted by RACK1 depletion in normal cells. Two potential mechanisms whereby RACK1 regulates mitotic exit are identified: suppression of Src-mediated Sam68 phosphorylation and maintenance of the cyclin-dependent kinase (CDK) 1-cyclin B complex in an active state. Our results reveal novel mechanisms of cell cycle control in G(1) and mitosis of colon cells. The significance of this work lies in the discovery of a mechanism by which the growth of colon cancer cells can be slowed, by RACK1 suppression of an oncogenic kinase at critical cell cycle checkpoints. Small molecules that mimic RACK1 function may provide a powerful new approach to the treatment of colon cancer.

Does being against euthanasia legislation equate to being anti-euthanasia?

This study investigated issues raised in qualitative data from our previous studies of health professionals and community members, which suggested that being opposed to euthanasia legislation did not necessarily equate to being anti-euthanasia per se. A postal survey of 1002 medical practitioners, 1000 nurses and 1200 community members was undertaken. In addition to a direct question on changing the law to allow active voluntary euthanasia (AVE), four statements assessed attitudes to euthanasia with or without a change in legislation. Responses were received from 405 doctors (43%), 429 nurses (45%) and 405 community members (38%). Compared with previous studies there was a slight increase in support for a change in the law from medical practitioners, a slight decrease in support from community members and almost no change among nurses. Different interpretations of the results of the four attitude questions are possible, depending on the perspective of the interpreter.

The evolution of Pseudomonas aeruginosa during antibiotic rotation in a medical intensive care unit: the RADAR-trial.

Bacterial spread between patients may contribute to the high prevalence of antibiotic-resistant pathogens within ICUs. The aim of this study was to evaluate the fate of Pseudomonas aeruginosa during the different antibiotic regimens. Susceptibility patterns and genotyping were performed to determine whether there was a predominant clone and to track the spread of resistant strains within the unit. Twenty-eight different ribotypes were found among 82 Pseudomonas isolates. Four ribotypes accounted for 42 (51%) isolates and were designated the "major clones" occurring throughout multiple cycles. The ribotypes with multiple occurrences were more resistant to antibiotics than ribotypes that appeared only once. The correlation of antibiotic use with antibiotic resistance and the finding of a large number of ribotypes suggested that de novo development of antibiotic resistance is a likely event in P. aeruginosa. In addition, ribotypes associated with antibiotic resistance appeared to have a survival advantage and can become frequent colonizers in the ICU.