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Biomedical subjects

N W Scott

Publications and source records attributed to N W Scott.

At least 19 recordsLinked to original sources

The use of differential item functioning analyses to identify cultural differences in responses to the EORTC QLQ-C30.

INTRODUCTION: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is a widely used health-related quality of life instrument. The main aim of this study is to investigate whether there are international differences in response to the questionnaire that can be explained by cultural factors. METHODS: Analyses involved a database of 106 separate studies including data from over 28,000 respondents. Differential item functioning (DIF) analyses using logistic regression were conducted for each item of the EORTC QLQ-C30 with respect to cultural/geographic group. Results were qualitatively compared with previously reported DIF analyses by translation to explore whether the source of the DIF was more likely to be linguistic or cultural in nature. RESULTS: Although most response patterns were similar, there were a number of international differences in how the questionnaire was answered. The largest variations were found in the results for Eastern Europe and East Asia. Results for the UK, the US and Australia tended to be similar. Many of the European results followed patterns that were more clearly explained when grouped by translation than when grouped by geographical region. DISCUSSION: Our results suggest that, in general, the EORTC QLQ-C30 is suitable for use in a wide variety of countries and settings. Some response variations that have the potential to affect the results of international studies were identified, but it was not always clear whether the source of the variation was primarily linguistic or cultural.

Adult↗

Comparing translations of the EORTC QLQ-C30 using differential item functioning analyses.

The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 is one of the most widely used quality of life instruments for cancer patients. The aim of this study was to assess whether there were linguistic differences in the way an international sample answered the EORTC QLQ-C30 questionnaire. Thirteen translations of the EORTC QLQ-C30, representing 22 countries, were investigated using a database of 27,891 respondents, incorporating 103 separate studies. Differential item functioning (DIF) analyses were conducted using logistic regression to identify items which, after controlling for subscale, were answered differently by language of administration. Both uniform and non-uniform DIF were assessed. Although most languages showed similar results to English, at least one instance of statistically significant DIF was identified for each translation, and a few of these differences were large. In some cases, the patterns were supported by the results of qualitative interviews with bilingual people. Although, overall, there appeared to be good linguistic equivalence for most of the EORTC QLQ-C30 items, several scales showed strongly discrepant results for some translations. Some of these effects are large enough to impact on the results of clinical trials. Based on our experience in this study, we suggest that validation of translations of health-related quality of life instruments should include exploration of DIF.

Attitude to Health↗

Randomized comparison of reduction and fixation, bipolar hemiarthroplasty, and total hip arthroplasty. Treatment of displaced intracapsular hip fractures in healthy older patients.

BACKGROUND: Orthopaedic surgeons vary in their management of displaced intracapsular fractures of the hip in healthy older patients. The aim of this investigation was to determine the functional, clinical, and resource consequences of three different types of surgical treatment. METHODS: The study was a multicenter randomized controlled trial. Reduction and fixation was compared with bipolar hemiarthroplasty with cement and total hip replacement with cement. Participating surgeons elected to randomize their patients to be treated with either one of the three types of procedures or with either fixation or bipolar hemiarthroplasty. Functional outcomes were measured with a hip-rating questionnaire and the EuroQol health status measure. Clinical outcomes included mortality and complications. The direct health service costs were compared. Participants were followed up for two years. RESULTS: Two hundred and seven patients were randomized to be treated with one of the three operations, and ninety-one were randomized to be treated with either fixation or bipolar hemiarthroplasty. There were no differences in the mortality rates among the treatment groups. The rate of secondary surgery was highest in the fixation group (39% compared with 5% in the group treated with bipolar hemiarthroplasty and 9% in the group treated with total hip replacement). The fixation group had the worst hip-rating-questionnaire and EuroQol scores at four and twelve months. The total hip replacement group had significantly better functional outcome scores at twenty-four months than the other two groups. Although fixation was initially the least costly procedure, this short-term advantage was eroded by significantly higher costs for subsequent hip-related hospital admissions. CONCLUSIONS: Arthroplasty is more clinically effective and cost-effective than reduction and fixation in healthy older patients with a displaced intracapsular fracture of the hip. The long-term results of total hip replacement may be better than those of bipolar hemiarthroplasty.

Aged↗

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome.

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7-12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery.

Age Factors↗

Displaced intracapsular hip fractures in fit, older people: a randomised comparison of reduction and fixation, bipolar hemiarthroplasty and total hip arthroplasty.

OBJECTIVES: To compare internal fixation, bipolar hemiarthroplasty and total hip arthroplasty for the management of displaced subcapital fracture of the hip in previously fit patients of 60 years or older. DESIGN: A prospective randomised clinical trial. SETTING: This multicentre trial was carried out in 11 Scottish hospitals with acute orthopaedic trauma units. PARTICIPANTS: The participants were 298 previously fit patients of 60 years or older with displaced subcapital hip fractures. INTERVENTIONS: The three surgical interventions for comparison were reduction and fixation, bipolar hemiarthroplasty and total arthroplasty (total hip replacement). Participating surgeons elected to randomise patients either among all three types of operation (three-way randomisation) or just between fixation and hemiarthroplasty (two-way randomisation). MAIN OUTCOME MEASURES: Clinical outcomes were mortality rates, reoperation rates and the complication rates associated with each procedure. Functional outcome was measured using a hip specific questionnaire [Johanson Hip Rating Questionnaire (HRQ)] and a general health status questionnaire [EuroQol 5 Dimensions (EQ-5D)]. Economic analysis compared the costs in the randomised groups of hospital treatment for the initial and subsequent admissions for up to 2 years. RESULTS: Altogether, 207 patients were randomised among all three trial operations, and 91 between just fixation and bipolar hemiarthroplasty. There were no statistically significant differences in clinical outcomes, but confidence intervals (CIs) were wide. At 2 years fixation failure reached 37% among those allocated fixation and 39% had undergone further surgery. Further surgery rates after hemiarthroplasty and total hip replacement were 5% and 9%, respectively. The group allocated fixation had significantly worse HRQ and EQ-5D scores than both arthroplasty groups at 4 and 12 months. At 24 months the results still favoured arthroplasty, but the overall HRQ and EQ-5D scores were no longer statistically significant. Total hip replacement had the best patient-assessed outcome scores. At 24 months the overall HRQ and EQ-5D scores for total hip replacement were significantly better than for hemiarthroplasty. The mean costs for the initial episode ranged from 6384 pounds Sterling for fixation to 7633 pounds Sterling for total hip replacement. The cost differences were largely due to differences in theatre costs and the cost of prostheses and hardware. The cumulative cost over 2 years of hemiarthroplasty was around 3000 pounds Sterling lower than for fixation (95% CI 1227 pounds Sterling to 7192 pounds Sterling). Compared with total hip replacement, both fixation and hemiarthroplasty were characterised by increased costs arising from hip-replacement admissions. When total (initial episode and subsequent hip-related admissions) hip-related costs are compared, total hip replacement conferred a cost advantage of around 3000 pounds Sterling per patient (versus hemiarthroplasty, 95% CI -pounds Sterling 1400 to 7420 pounds Sterling). CONCLUSIONS: In fit, older patients the results of the study show a clear advantage for arthroplasty over fixation; arthroplasty was more clinically effective and probably less costly over a 2-year period postsurgery. The results suggest that total hip replacement has long-term advantages over bipolar hemiarthroplasty, but these findings are less definite. This study provided support for the use of total hip replacement to treat displaced intracapsular hip fractures in fit, older patients. A larger trial comparing total versus hemiarthroplasty for these fractures could help to verify these findings. It would also be useful to know whether the findings of this study apply to patients aged 60 years or less who are usually treated with reduction and fixation. A clinical trial comparing arthroplasty versus fixation in patients older than 40 years would be a logical extension of the current study.

Aged↗

Five-year follow-up of a randomized trial to assess pain and numbness after laparoscopic or open repair of groin hernia.

BACKGROUND: Claims that laparoscopic groin hernia repair is followed by less persisting pain and numbness than open mesh repair were tested by follow-up within a multicentre randomized clinical trial. METHODS: Participants in the UK Medical Research Council Laparoscopic Groin Hernia Trial were followed up by means of self-completed postal questionnaires from 2 to 5 years after trial entry. The principal measures were pain (groin and testicular) and numbness (groin and thigh). RESULTS: Seven hundred and fifty (80.8 per cent) of the original 928 participants returned at least one questionnaire between 2 and 5 years; respondents were similar to the baseline randomized groups. Fewer respondents in the laparoscopic group had groin pain (absolute differences varied between 7.9 and 2.0 per cent, but were of marginal statistical significance); rates of testicular pain were similar in the two groups. Groin numbness was reported about half as commonly at all time points in the laparoscopic group (P < 0.001); there were no significant differences in thigh numbness. CONCLUSION: Laparoscopic surgery was associated with less long-term numbness and probably less pain in the groin.

Follow-Up Studies↗

Does early imaging influence management and improve outcome in patients with low back pain? A pragmatic randomised controlled trial.

OBJECTIVES: To establish whether the early use of sophisticated imaging techniques influences the clinical management and outcome of patients with low back pain (LBP) and whether it is cost-effective. DESIGN: A pragmatic multicentre randomised controlled trial using a standard two parallel group approach incorporating an economic evaluation. For a subgroup of trial participants, a controlled 'before and after' approach was used to assess the impact of 'early imaging' on clinicians' diagnostic and therapeutic confidence. SETTING AND PARTICIPANTS: A total of 782 participants who had been referred by their general practitioner to a consultant orthopaedic specialist or neurosurgeon because of symptomatic lumbar spine disorders. The study included 14 hospitals in Scotland and one in England over a 24-month period. RESULTS: Participants in both groups reported an improvement in health status at 8 and 24 months with the 'early imaging' group having statistically significantly better outcome. Other than the proportion of participants receiving imaging (90% versus 30%), there were few differences between the groups in the management received throughout the 24-month follow-up. The total number of outpatient consultations in the two groups was similar although more people in the 'early imaging' group had return outpatient appointments during the 8-month follow-up. Clinicians' diagnostic confidence, between trial entry and follow-up, increased significantly for both groups with a greater increase in the 'early imaging' group. The cost of imaging was the main determinant of the difference in total costs between the groups and it was estimated that 'early imaging' could provide an additional 0.07 quality-adjusted life-years (QALYs), at an additional average cost of 61 British pounds over the 24-month follow-up. Using non-imputed costs and QALYs but adjusted for baseline differences in EQ-5D score, the mean incremental cost per QALY of 'early imaging' was 870 British pounds. The results were sensitive to the costs of imaging and the confidence intervals surrounding estimates of average costs and QALYs. CONCLUSIONS: The early use of sophisticated imaging does not appear to affect management overall but does result in a slight improvement in clinical outcome at an estimated cost of 870 British pounds per QALY. Imaging was associated with an increase in clinicians' diagnostic confidence, particularly for non-specialists. Further research is required to determine if more rapid referral to sophisticated imaging and secondary care is important in the acute episode and whether the use of imaging would be more beneficial for particular categories of LBP.

Adult↗

Laparoscopic techniques versus open techniques for inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is the most frequently performed operation in general surgery. The standard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh. This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique. Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia, most individual trials have been too small to show clear benefits of one type of surgical repair over another. OBJECTIVES: The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques. Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and The Cochrane Central Controlled Trials Registry for relevant randomised controlled trials. The reference list of identified trials, journal supplements, relevant book chapters and conference proceedings were searched for further relevant trials. Through the EU Hernia Trialists Collaboration (EUHTC) communication took place with authors of identified randomised controlled trials to ask for information on any other recent and ongoing trials known to them. Specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials. The world wide web was also searched. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic groin hernia repair with open groin hernia repair were eligible for inclusion. Trials were included irrespective of the language in which they were reported. DATA COLLECTION AND ANALYSIS: Individual patient data were obtained, where possible, from the responsible trialist for all eligible studies. All reanalyses were cross-checked by the reviewers and verified by the trialists before inclusion. Where IPD were unavailable additional aggregate data were sought from trialists and published aggregate data checked and verified by the trialists. IPD were available for 25 trials, additional aggregated data for seven and published data only for nine. Where possible, time to event analysis for hernia recurrence and return to usual activities were performed on an intention to treat principle. The main analyses were based on all trials. Sensitivity analyses based on the data source and trial quality were also performed. Pre-defined subgroup analyses based on recurrent hernias, bilateral hernias and femoral hernias were also carried out. MAIN RESULTS: 41 published reports of eligible trials were included involving 7161 participants. Sample sizes ranged from 38 to 994, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (WMD 14.81 minutes, 95% CI 13.98 to 15.64; p<0001). Operative complications were uncommon for both methods but more frequent in the laparoscopic group for visceral (Overall 8/2315 versus 1/2599) and vascular (Overall 7/2498 versus 5/2758) injuries. Length of hospital stay did not differ between groups (WMD -0.04 days, 95% CI -0.08 to 0.00; p=0.05, but return to usual activity was earlier for laparoscopic groups (HR 0.56, 95%CI 0.51 to 0.61; p<0.0001 - equivalent to 7 days). The data available showed less persisting pain (Overall 290/2101 versus 459/2399; Peto OR 0.54, 95% CI 0.46 to 0.64; p<0.0001), and less persisting numbness (Overall 102/1419 versus 217/1624; Peto OR 0.38, 95% CI 0.4286 to 0.49; p<0.0001) in the laparoscopic groups. In total, 86 recurrences were reported amongst 3138 allocated laparoscopic repair and 109 amongst 3504 allocated to open repair (Peto OR 0.81, 95% CI 0.61 to 1.08; p = 0.16). The use of mesh during laparoscopic hernia repair is associated with a reduction in the risk of hernia recurrence, significantly so for the transabdominal preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus 47/1119; Peto OR 0.45, 95% CI 0.28 to 0.72; p=0.0009). However, no difference was detected when comparing laparoscopic methods with open mesh methods of hernia repair. REVIEWER'S CONCLUSIONS: The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%. However, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. The data suggests less persisting pain and numbness following laparoscopic repair. Return to usual activities is faster. However, operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral (especially bladder) and vascular injuries.

Hernia, Inguinal↗

Open mesh versus non-mesh for repair of femoral and inguinal hernia.

BACKGROUND: Inguinal hernia repair is the most frequent operation in general surgery. Until recently the standard procedure has been open musculo-aponeurotic repair using sutures under tension to close the defect but 'tension-free' repair using prosthetic mesh is becoming increasingly common in many countries. OBJECTIVES: The purpose of this review is to evaluate open mesh techniques in comparison with open non-mesh techniques for the surgical repair of groin hernia. SEARCH STRATEGY: Electronic databases were searched and further trials were sought from the reference lists of reports of known trials. Through the EU Hernia Trialists Collaboration authors of identified randomised controlled trials were asked for information on any other trials known to them. There was no language restriction. SELECTION CRITERIA: Studies were eligible for inclusion if they were randomised or quasi-randomised trials comparing either a) open mesh with open non-mesh repair of groin hernia or b) open flat mesh repair with plug and mesh repair of groin hernia. DATA COLLECTION AND ANALYSIS: For each outcome the results were derived using data from the best available source. The majority of data for this review came from individual patient data (IPD) supplied by the trialists. When these were unavailable data came from additional aggregated information or from published trial reports. All trials were analysed using the 'intention to treat' principle. MAIN RESULTS: Twenty trials comparing open mesh with open non-mesh repair were identified. Open mesh methods, on average, took 7-10 minutes less to perform than Shouldice procedures, but took 1-4 minutes longer than other non-mesh methods. There were no clear differences between mesh and non-mesh groups for haematomas, seromas or wound/superficial infections. Three serious operative complications were reported after open mesh repair and three following non-mesh repair. Overall, those in the mesh groups had a shorter length of hospital stay and quicker return to usual activities, but this pattern was not observed for all trials. There was a suggestion that persisting pain was less frequent after mesh repair than after non-mesh repair but this result was dependent on one trial and data were not available for 11 trials. There was no evidence of a difference between the groups with respect to persisting numbness. Fewer hernia recurrences were reported after mesh repair (Peto OR: 0.37, 95% CI: 0.26 to 0.51). There were too few data to reliably address differential effects for patients with recurrent, bilateral or femoral hernias. Two trials comparing flat mesh with plug and mesh were identified. There was no clear evidence of differences between the groups. REVIEWER'S CONCLUSIONS: There is evidence that the use of open mesh repair is associated with a reduction in the risk of recurrence of between 50% and 75%. Although the trials were heterogeneous there is also some evidence of quicker return to work and of lower rates of persisting pain following mesh repair.

Clinical Trials as Topic↗

Use of the GFP reporter as a vital marker for Agrobacterium-mediated transformation of sugar beet (Beta vulgaris L.).

Molecular approaches to sugar beet improvement will benefit from an efficient transformation procedure that does not rely upon exploitation of selectable marker genes such as those which confer antibiotic or herbicide resistance upon the transgenic plants. The expression of the green fluorescent protein (GFP) signal has been investigated during a program of research that was designed to address the need to increase the speed and efficiency of selection of sugar beet transformants. It was envisaged that the GFP reporter could be used initially as a supplement to current selection regimes in order to help eliminate "escapes" and perhaps eventually as a replacement marker in order to avoid the public disquiet associated with antibiotic/herbicide-resistance genes in field-released crops. The sgfp-S65T gene has been modified to have a plant-compatible codon usage, and a serine to threonine mutation at position 65 for enhanced fluorescence under blue light. This gene, under the control of the CaMV 35S promoter, was introduced into sugar beet via Agrobacterium-mediated transformation. Early gene expression in cocultivated sugar beet cultures was signified by green fluorescence several days after cocultivation. Stably transformed calli, which showed green fluorescence at a range of densities, were obtained at frequencies of 3-11% after transferring the inoculated cultures to selection media. Cocultivated shoot explants or embryogenic calli were regularly monitored under the microscope with blue light when they were transferred to media without selective agents. Green fluorescent shoots were obtained at frequencies of 2-5%. It was concluded that the sgfp-S65T gene can be used as a vital marker for noninvasive screening of cells and shoots for transformation, and that it has potential for the development of selectable marker-free transgenic sugar beet.

Base Sequence↗

RS2: a sugar beet gene related to the latex allergen Hev b 5 family.

A novel gene (RS2) has been isolated from a Beta vulgaris (cv. Regina) cDNA library. The expression of this gene was enhanced in the mature storage organ as compared to leaf tissue. The protein encoded by this gene was found to be alanine- and glutamic acid-rich and it resembles members of the latex allergen Hev b 5 family.

Allergens↗

The plant cell cycle in context.

Biological scientists are eagerly confronting the challenge of understanding the regulatory mechanisms that control the cell division cycle in eukaryotes. New information will have major implications for the treatment of growth-related diseases and cancer in animals. In plants, cell division has a key role in root and shoot growth as well as in the development of vegetative storage organs and reproductive tissues such as flowers and seeds. Many of the strategies for crop improvement, especially those aimed at increasing yield, involve the manipulation of cell division. This review describes, in some detail, the current status of our understanding of the regulation of cell division in eukaryotes and especially in plants. It also features an outline of some preliminary attempts to exploit transgenesis for manipulation of plant cell division.

Amino Acid Sequence↗

PCR and non-isotopic labeling techniques for plant virus detection.

PCR technology permits the detection of viruses at levels several orders of magnitude lower than is possible by other methods. This high sensitivity facilitates detection of virus sequences during the early stages of infection of plants and in soil and vector samples. Early detection of beet necrotic yellow vein virus (BNYVV) in Beta vulgaris is an important part of the strategy for prevention of the spread of rhizomania, a commercially significant disease of sugar beet. A diagnostic test for BNYVV has been developed. This test involves amplification of the viral genome by PCR coupled with non-isotopic labeling and detection of specific sequences. The PCR amplification of BNYVV sequences has been optimized with respect to primer design, sample preparation and reaction conditions. Several non-isotopic labeling strategies for signal amplification have been compared. Hybridization with digoxigenin-labelled cDNA permits the most sensitive detection of PCR products and is the most appropriate method for routine diagnosis. These observations are discussed in the context of the application of PCR for detecting a wide range of viruses.

Base Sequence↗

The identification, cloning, and sequence analysis of the coat protein coding region of a birch isolate (I2) of cherry leaf roll nepovirus.

The coat protein gene of RNA-2 of cherry leaf roll nepovirus (CLRV) birch isolate I2 was cloned, identified, and sequenced. Transcripts derived from cDNA to the coat protein gene made a polypeptide of M(r) 51.5 k when translated in vitro. The predicted amino acid sequence of the coat protein showed little identity with nepoviruses having small RNA-2s. It did, however, have 27% sequence identity with the coat protein of tomato ringspot nepovirus which, like CLRV, has a relatively large RNA-2.

Amino Acid Sequence↗

A 1.5 kb sequence homology in 3'-terminal regions of RNA-1 and RNA-2 of a birch isolate of cherry leaf roll nepovirus is also present, in part, in a rhubarb isolate.

A series of cDNA clones has been made from the birch isolate of cherry leaf roll nepovirus. Restriction enzyme analysis and sequencing showed that at the 3' end, RNA-1 and RNA-2 are identical for 1.5 kb. Also a 0.7 kb 3' end homology exists between the birch and rhubarb isolate. These sequences do not seem to code for any proteins; however, the sequence conservation points to a role in virus replication.

Base Sequence↗

Purification and partial characterization of DNA-dependent RNA polymerase from Rhodomicrobium vannielii.

DNA-dependent RNA polymerase has been isolated from Rhodomicrobium vannielii. Like those from other eubacteria, the enzyme contained four subunits: beta and beta prime (Mr 155,000), alpha (Mr 38,000), and sigma (Mr 98,000). Analysis by isoelectric focussing showed that both alpha and sigma had several forms with different isoelectric pH values. The enzyme was sensitive to rifampicin (5 ng rifampicin ml-1 gave 50% inhibition) and capable of specific promoter selection with DNA from R. vannielii, calf thymus and phage T7D111.

Chromatography, Gel↗

Mecillinam susceptibility of Escherichia coli K-12 mutants deficient in the adenosine 3',5'-monophosphate system.

The mecillinam resistance of Escherichia coli K-12 mutants deficient in the enzyme responsible for the synthesis of adenosine 3',5'-monophosphate, adenylate cyclase, has been investigated. The results suggest that resistance to this antibiotic may be a consequence of the slow growth rate of these mutants rather than an intrinsic property of their genetic lesion.

Amdinocillin↗