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CYP2C19-guided voriconazole dosing reduces pharmacokinetic variability, but many patients remain subtherapeutic. The aim of this study was to evaluate the effect of candidate genes and a novel CYP2C haplotype on voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. This is a retrospective candidate gene study in allogeneic hematopoietic cell transplant (HCT) patients receiving CYP2C19-guided voriconazole dosing. Patients were genotyped for ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C haplotype were genotyped. Of 185 patients, 36% were subtherapeutic (of which 79% were normal or intermediate metabolizers). In all patients, CYP2C19 (p CYP2C19 (p = 0.004) and ABCG2 (p = 0.015) were associated with voriconazole concentrations; CYP2C19 (p = 0.028) and letermovir use (p = 0.001) were associated with subtherapeutic status. CYP2C19, ABCG2, age, and letermovir use were associated with voriconazole concentrations and may be used to improve voriconazole precision dosing.

Background For soccer athletes, injuries are frequent and pose a considerable health and financial burden for individuals and families. While studies have previously assessed the incidence of soccer injuries and preventive strategies male athletes use to reduce these occurrences, few have included women and players of varying skill levels. Objective To report the frequency of injuries in a cohort of male and female soccer athletes and describe the training habits that have helped prevent injury. Methods Two hundred (n=200) United States participants completed a questionnaire on soccer practicing frequency, habits, injuries, and treatments. A screening question ensured all respondents had played soccer for at least one year and determined eligibility for the study. Participant information related to age, sex, education, income, and race was also collected. JMP statistical software was used to analyze collected data and build multivariate regressions, mosaic plots, and histograms. Results The mean number of practice sessions per week was 3.60 +/- 1.64, and the median experience playing soccer was 2-4 years. Older participants were more likely to practice once (p = 0.0001) or twice (p= 0.0008) per week. Women were less likely to include warmups before playing soccer (p = 0.022). This was problematic as participants who did not include a proper warmup routine were more likely to have been absent from play for longer amounts of time following injury (p = 0.032). The four most common injury sites were knees (n = 35, 17.5%), ankles (n = 31, 15.5%), shoulders (n = 25, 12.5%), and head/neck (n = 24, 12%). 140 (47.62%) patients used pain medication as their main remedy, 128 (43.54%) went to physical therapy, and 26 (10.78%) underwent surgery. Conclusion In any sample of soccer athletes involving variations in sex, race, and competitive play, injuries are highly common. Few studies before this one have included female athletes, and our findings highlight an important discrepancy in training habits between sexes. Women are less likely to follow a warmup regimen and are thus injured for longer. Incorporating dynamic stretching and plyometrics are particularly helpful to stay healthy.

1000 SNPs with greatest statistical association with cumulative docetaxel dose at grade 3+ neuropathy in CALGB 90401 discovery GWAS.

Peripheral neuronal cells (Peri.4U) treated with docetaxel were found to have a significant decrease in sensitivity for A) mean process lengths but not for B) mean outgrowth intensity or C) relative straightness as measured after 24 hours post-drug treatment. For paclitaxel treatment at the same time point, the cells were also found to have significantly decreased sensitivity for D) relative mean process length and E) mean outgrowth intensity but not for F) relative straightness. Neurite parameters measured with MetaXPress® software were averaged from 3 independent experiments. Error bars represent the standard error of the mean from three independent transfection experiments. NTC = non-targeting control, UT= untransfected control.

Number of patients who experienced neuropathy, completed treatment without neuropathy and discontinued treatment early without having neuropathy while on study and within each range of cumulative treatment.

Sensitivity to mechanical stimuli with Von Frey filaments for C57BL/6J mice and litter-mates heterozygous for VAC14 prior to docetaxel treatment. The figure displays the estimate of the proportion of mice without a hind-paw withdrawal response to stimulation by each Von Frey fiber weight, e.g., no mice respond to fibers {less than or equal to}0.2 g and all mice respond to fibers{greater than or equal to}1.4 g. The VAC14 heterozygous mice (hatched line) are more likely than wild-type mice (solid line) to respond, meaning they are more sensitive to nociceptive stimuli (p=0.0012). Gray lines denote 95% confidence intervals.

CONSORT diagram illustrating patient flow from enrollment on parent study to population included in pharmacogenetic discovery analysis and quality control filtering of SNPs from the Illumina HumanHap610-Quad into the pharmacogenetic analysis.

Most Highly Enriched Canonical Pathways

Purpose: Discovery of SNPs that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy.Experimental Design: A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy.Results: A total of 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1,000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. An SNP in VAC14 (rs875858) surpassed genome-wide significance (P = 2.12 × 10−8, adjusted P = 5.88 × 10−7). siRNA knockdown of VAC14 in stem cell–derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (P = 0.0015) and branches (P < 0.0001). Prior to docetaxel treatment, VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (P = 0.001).Conclusions: VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization. Clin Cancer Res; 22(19); 4890–900. ©2016 AACR.

The authors present the case of a patient who was brought to the emergency department (ED) with severe left forearm pain following a classroom fall. This incident exacerbated the fractures that the patient experienced three months earlier in an accident. He had partial fractures of the middle radial and ulnar diaphyses. A review of the various presentations of forearm fractures and the nonoperative and surgical treatment options are discussed.

Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (

The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP &gt, 20 ng/mL, AFP-L3 &gt, 15%, and DCP &gt, 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with &lt, 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.

Due to the sever circumstances in the global pandemic, there has been an immense need for disinfectant robot technology. This pandemic has made people much more aware about the severity of virus transmission in public areas. This prompts society to be much more aware of the need to maintain a clean environment. The purpose of this paper is to present the design principles of an Autonomous Indoor Cleaning Robot (AICR) developed to reduce the spread of COVID-19 in indoor environments such as small shops and office settings. Its main purpose is to proactively disinfect the air and maintain a clean breathing environment by actively targeting populated areas with the use of a vision system, using Visual Simultaneous Localization and Mapping (VSLAM) technology. Currently there are other air disinfection products on the market also making use of a combination of a High-Efficiency Particulate Absorbing (HEPA) air purifier and Ultra Violet (UV) light to kill airborne viruses like the Coronavirus. However, all of these are stationary with lack of intelligence machines that have to be kept or manually wheeled from room to room. The device proposed in the paper is a fully autonomous air purifying device capable of going to certain critical regions of the indoor environment to disinfect the air in that area without any human interaction. The stationary purifiers should be much more powerful covering a larger area which makes them very expensive. In contrast, the developed autonomous air purifier needs much less power consumption compared to static purifiers, with the advantage of intelligently and dynamically learning the status of the room using the information captured from the occupancy, itself, and the environment.

Chimaeric antigen receptor (CAR) T cells can generate durable clinical responses in B-cell haematologic malignancies. The manufacturing of these T cells typically involves their activation, followed by viral transduction and expansion ex vivo for at least 6 days. However, the activation and expansion of CAR T cells leads to their progressive differentiation and the associated loss of anti-leukaemic activity. Here we show that functional CAR T cells can be generated within 24 hours from T cells derived from peripheral blood without the need for T-cell activation or ex vivo expansion, and that the efficiency of viral transduction in this process is substantially influenced by the formulation of the medium and the surface area-to-volume ratio of the culture vessel. In mouse xenograft models of human leukaemias, the rapidly generated non-activated CAR T cells exhibited higher anti-leukaemic in vivo activity per cell than the corresponding activated CAR T cells produced using the standard protocol. The rapid manufacturing of CAR T cells may reduce production costs and broaden their applicability.

Background: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)–targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. Methods: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16–22) and 25 healthy control subjects underwent dynamic brain 11C-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (2 p = .09; F 1,71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t 74 = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t 54 = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. Conclusions: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

In pushing for a republic, then prime minister of New Zealand, Jim Bolger, once stated that ‘the tide of history is moving in one direction’; more recently, former prime minister and self-confessed...

Carotid artery pseudoaneurysm is a rare but serious complication of a retropharyngeal abscess in children. We report the first case of treating an unruptured mycotic pseudoaneurysm of the extracranial internal carotid artery (ICA) in a pediatric patient with vascular plugs. A 3-year-old patient presented with airway compromise and signs of neck sepsis. Successful embolization of the pseudoaneurysm was achieved with 2 Amplatzer vascular plugs to close the front and back door. The patient did not have any neurological deficit. Repeat imaging with ultrasound and computed tomography confirmed no recurrence of the pseudoaneurysm.

Background & Aim The recent success of immunotherapy using chimeric antigen receptor modified T cells (CAR T) in B-cell malignancies highlights the potential of these cytotoxic “drugs” for cancer therapy. CAR T therapies generally relies upon viral transduction of T cell-receptor (TCR) activated T cell followed by ex vivo expansion of patient-derived T cells over days to weeks prior to infusion. In addition to the required time and labor, we previously reported that TCR/CD3 activation and ex vivo expansion leads to progressive differentiation of the CAR T cells with associated loss of CAR T cell potency. Since cell division is not a prerequisite for lentiviral vector-mediated gene delivery, we hypothesized that elimination of the CD3/CD28 activation step would yield a T cell product with high functional potency. Methods, Results & Conclusion Here, we show that functional CD19-specific CAR T cells (CART19) can be generated in as little as 24 hours using lentiviral vectors without the need for prior T cell activation. We further demonstrate that some of the restriction factors that limit the infection of quiescent T cells can be overcome by changes to the medium formulation. Most importantly, we show that non-activated T cells exhibit potent antitumor function with deep and durable control of leukemia achieved in vivo with greater than 1-log fewer CD19-specific CAR T cells compared with a 9-day process currently used by tisagenlecleucel (Fig. 1). These findings confirmed that as few as an estimated 12,000-32,000 non-activated CAR T cells produced within 24 hours from mononuclear cell collection could eradicate leukemia. These results demonstrate the potential for vastly reducing the time, materials and labor required to generate CAR T cells, which could be especially beneficial in patients with rapidly progressive disease and in resource-poor health care environments.

The recent success of immunotherapy using chimeric antigen receptor modified T cells (CAR T) in B-cell malignancies highlights the potential of these cytotoxic "drugs" for cancer therapy. CAR T therapies generally rely upon manufacturing approaches that include prior T cell activation through engagement of the TCR and costimulatory receptors followed by ex vivo expansion of patient-derived T cells over days to weeks. We previously reported that CD3/CD28 stimulation prior to transduction promotes progressive T cell effector differentiation over time in culture with loss of CAR T cell potency (Ghassemi et al. 2018 PMID: 30030295). Since cell division is not a prerequisite for lentiviral vector-mediated gene delivery, we hypothesized that lentiviral transduction of quiescent T cells without prior activation will enhance engraftment and persistence of CART cells that is associated with long-term leukemia control. Here, we show that functional CD19-specific CAR T cells (CART19) can be generated in as little as 24 hours using lentiviral vectors without the need for prior T cell activation. We showed using a non-optimized process that a mean of 6.5% (range 2%-10%) of freshly isolated quiescent T cells can be transduced using an infrared red fluorescent protein (iRFP)-expressing lentiviral vector with slower kinetics of expression compared with activated T cell transduction (peak at 96 hrs vs. 48 hrs for quiescent and activated T cells, respectively). Although substantially less efficient compared to activated T cells, transduction was detected across all T cells subsets with central memory T cells showing the greatest transduction efficiency with a mean of 4-fold greater transduction compared with naïve T cells. Somewhat unexpectedly, CART19 cells generated from quiescent T cells using a CD19-specific CAR vector showed a 3-5 fold greater transgene expression compared with iRFP vectors transduced at similar MOI. However, we show that CAR expression can occur in quiescent T cells even without reverse transcription or integrase function, so called "pseudotransduction". Importantly, we show that this CAR expression produces T cells with cytolytic activity and effector cytokine production in response to antigen that is similar to activated and transduced CAR T cells. Using the well-characterized Nalm6 model of acute lymphoblastic leukemia, we show that CART19 cells generated by transduction of quiescent T cells for 16 hours followed by washing to remove vector exhibit dose-dependent anti-leukemic activity that is durable with injection of as little as 2x105 total T cells. We estimate the latter to contain ~2x104 T cells with integrated lentiviral vector based upon transduction efficiency determined in studies using non-tumor bearing mice. (Fig 1). In summary, our results support the need for further investigation of CAR T cells that are generated using engineering of quiescent T cells. Taking advantage of the ability of lentiviral vectors to transfer genes to quiescent T cells, the highly abbreviated and simplified manufacturing approach described here has the potential to enhance therapeutic potency while also substantially reducing the materials and labor costs associated with current manufacturing approaches that use activated and expanded T cells. In addition, the rapid nature of this manufacturing has the potential to extend the population of patients that may be treated with these therapies by shortening the interval between aphaeresis collection and re-infusion of CAR T cells, which prevents the treatment of some patients with rapidly progressive disease. Disclosures Ghassemi: Novartis: Patents & Royalties. Milone:Novartis: Patents & Royalties, Research Funding.

We report a unique case of neonatal mycotic internal iliac artery aneurysm managed non-operatively. The child had multifocal osteomyelitis and no history of umbilical artery catheterisation. The aneurysm was regularly scanned and monitored until its obliteration by thrombus 17 days after initial detection. Contingency plans for either interventional radiological coiling or open surgical repair were in place had the aneurysm grown or the child deteriorated.

The identification of a small number of monoclonal antibody (mAb) producing candidate cell lines from the large number of clones generated post transfection is one of the bottlenecks of cell line development. Clone numbers are reduced significantly during initial medium exchange and static scale up stages but significant numbers can still progress to evaluation in shaking cultures. This is often carried out in shake flasks where the number of clones that can be evaluated may be restricted due to resource limitations. The Duetz Microflask system is a microtitre plate based system which uses ‘Sandwich Covers’ to convert the individual wells of 24 well plates into individual ‘mini reactors’. The ‘Sandwich Covers’ consist of a stainless steel cover, a 0.2µm filter, microfibre inlays and a flexible silicone sealing layer to ensure adequate oxygen transfer rates to individual wells. This work describes the use of the Duetz Microflask system to evaluate cell lines in culture prior to scale up to production shake flasks. We have compared the growth and rank order of performance for a number of cell lines in the Duetz Microflask system with data obtained from shake flasks and demonstrated this system can be used successfully to identify candidate cell lines for further progression. A series of preliminary experiments was completed to determine suitable volumes and operating conditions to minimise evaporation. Unless otherwise stated these were: Fill volume – 1.5mL, Shaker speed – 200rpm, Humidity – 80%.

Purpose To evaluate retrievability of the Celect vena cava filter over time and to assess the safety of the retrieval procedure in a prospective multicenter registry. Materials and Methods Between October 2005 and March 2008, Celect filters were placed in 95 patients (61 men; mean age, 51 years ± 18.5) with a temporary need for an inferior vena cava (IVC) filter. All patients satisfied requirements for filter placement; the primary indications for placement were pulmonary embolism (PE) with a contraindication to or failure of anticoagulation ( n = 40), high risk for further PE ( n = 29), trauma ( n = 23), or massive PE with residual deep vein thrombosis and risk for further PE ( n = 3). Filter orientation, vena cava injury, and other device-related incidents were evaluated at implantation and retrieval. The degree of difficulty associated with retrieval was also assessed. Results Filter retrieval was attempted in 58 patients (mean indwell time of 179 days; median, 168.5 d; range, 5–466 d). Fifty-six filters (96.6%) were successfully retrieved. Unsuccessful retrieval attempts were attributed to filter tilt ( n = 1) or excessive tissue growth with the hook embedded in the endothelium ( n = 1). No adverse events were associated with the inability to retrieve these filters. A Kaplan-Meier product-limit survival estimate revealed that the probability of successful filter retrieval remained at 100% at 50 weeks and at more than 74% at 55 weeks after implantation. No adverse events were related to the retrieval procedures. Conclusions Retrieval of the Celect filter was performed safely as long as 466 days after implantation.

OBJECTIVE—This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA1c. RESULTS—Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA1c and FPG. CONCLUSIONS—A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.

Thyroid hormone levels play an important role in cardiac regulation, and a state of hypothyroidism leads to dilated forms of cardiomypathy. Inappropriate thyroid levels can also impact the sarcomeric protein titin, which is responsible for maintaining passive tension and structural integrity. The effects of hypothyroidism were studied after administration of propylthiouracil (PTU) to wild type (Wt) and homozygous mutant (Hm) rats (Greaser et al J Mol Cellul Cardiol 44:983, 2008) (the latter of which express a giant titin isoform). Enzyme-linked immunosorbent assay results demonstrated that PTU lowered thyroxine levels in the treated rats. Electrophoretic cardiac myosin heavy chain analysis indicated that hypothyroidism induced a transition to predominantly beta myosin heavy chain expression, while Wt control samples continued to express an age-appropriate range of alpha and beta isoforms. PTU-treated Wt rats had a larger N2BA to N2B titin ratio, and the slower migrating N2BA was in higher proportion than the faster N2BA. PTU did not affect titin isoform expression in Hm. Because it is believed that thyroid hormone regulates titin isoform expression through the PI3K/Akt pathway, we investigated several participants by immunoblotting. The Akt PH domain was not altered by PTU administration, although expression was higher in Hm rats. Akt phospho-Ser473 did not vary between treatments, but mTOR phospho-Ser2448 demonstrated a higher phosphorylation state in Wt. Echocardiography data showed significantly decreased fractional shortening in Hm control, Hm PTU, and Wt PTU relative to Wt control. Wt control also exhibited a higher ejection fraction and a lower isovolumic relaxation time compared to the other treatments. It can be concluded that hypothyroidism has significant effects on titin isoform expression and other cardiac functional characteristics. Supported by NIH HL77196.

The development of monoclonal antibody (mAb) processes conventionally involves the generation of multiple cell lines in multiwell plates, cell line screening in shake flasks followed by final cell line selection and process optimisation in bioreactors. This process can typically take up to 18 months to generate a robust process suitable for early phase manufacturing and therefore any opportunity to streamline this process impacts directly on drug development timelines. This work describes the potential integration of the Micro-24 Bioreactor system (Pall Life Sciences) and the Duetz Microflask system (Applikon Biotechnology) into cell line development and early process development and demonstrates how these systems can be used for cell line evaluation and process optimisation. The Micro-24 Bioreactor system comprises 24 bioreactors (7ml working volume) each capable of independent temperature, dissolved oxygen and pH control. Cell cultures are carried out in a presterilised polycarbonate mammalian cell culture cassette with a central vent and are inoculated manually in a laminar flow cabinet before sealing with Type A single use closures and incubation under experimental conditions.