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Genetic testing is the mainstay for diagnosis of autoinflammatory diseases and there may be unidentified genes. A 2-year-old male presented for evaluation of recurrent fevers and infections.

Evaluation of clinical immunodeficiency is challenging given its broad variety of clinical presentations. It is essential to maintain a broad differential diagnoses with atypical presentations. We present a case of a patient with recurrent infections due to an underlying genetic condition.

Eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is a serine/tyrosine kinase which plays a role in protecting against viral infections. De novo pathogenic variants in the EIF2AK2gene have been associated with developmental delay, leukoencephalopathy, and neurological decompensation. We are reporting on a patient with pancytopenia and a memory phenotype of specific antibody deficiency in the setting of an EIF2AK2variant (c.973G>A (p.Gly325Ser)).

47 year-old male presented to the ED for intermittent chest pain, emesis, and early satiety for several months. He had elevated troponins, Cr 2.85, BNP 710, WBC 33K, but no ST-segment changes on serial EKGs. He was admitted to the cardiology service overnight. CTA abdomen/pelvis showed diffuse gastric wall thickening with upper abdominal and retroperitoneal lymphadenopathy. He was subsequently started on antiplatelet therapy and heparin, with a scheduled coronary angiography. However, patient became encephalopathic and agitated.

Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) often presents within the first year of life. Symptoms include fevers, chills, headache, lymphadenopathy, and abdominal pain. Patients may be misdiagnosed as other autoinflammatory syndromes, resulting in delay of treatment.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency caused by a gain-of-function mutation in CXCR4. A complication of WHIM syndrome is severe neutropenia, which can result in fatal bacterial infections. Given the rarity of the disease and variability of clinical presentations, WHIM syndrome can be difficult to diagnose and manage.

Adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) is characterized by severe lymphocytopenia affecting T, B and NK lymphocytes, with non-immunological manifestations including neurodevelopmental deficits and sensorineural deafness. Treatment modalities include enzyme replacement therapy(ERT) and/or autologous gene therapy or hematopoietic stem cell treatment. We report a 9-month-old female with ADA deficient T-B-NK+ SCID treated with ERT while awaiting stem cell treatment.

This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1–4 mg days 1–14), bortezomib (1–1.3 mg/m2days 1, 4, 8 and 11 for cycles 1–8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.

Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising therapeutic strategy for various hematologic cancers. Previous studies suggest that BET inhibitors constrain tumor cell proliferation and survival mainly through the suppression of MYCtranscription and activity. However, suppression of the transcription of additional genes also contributes to the antitumor activity of BET inhibitors but is less well understood. Here we examined the therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent cytotoxicity against MM cell lines and patient-derived MM cells through G1cell cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition overcomes the protective effects conferred by cytokines and bone marrow stromal cells. We also confirmed the in vivoefficacy of CPI-0610 in a MM xenograft mouse model. Our study found IKZF1and IRF4to be among the primary targets of CPI-0610, along with MYC. Given that immunomodulatory drugs (IMiDs) stabilize cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI-0610. Combination studies of CPI-0610 with IMiDs show in vitrosynergism, in part due to concomitant suppression of IKZF1, IRF4and MYC, providing a rationale for clinical testing of this drug combination in MM patients.

We have previously demonstrated that interleukin-17A (IL-17) producing T helper 17 cells are significantly elevated in blood and bone marrow (BM) in multiple myeloma (MM) and IL-17A promotes MM cell growth via the expression of IL-17 receptor. In this study, we evaluated anti-human IL-17A human monoclonal antibody (mAb), AIN457 in MM. We observe significant inhibition of MM cell growth by AIN457 both in the presence and the absence of BM stromal cells (BMSCs). Although IL-17A induces IL-6 production, AIN457 significantly downregulated IL-6 production and MM cell adhesion in MM–BMSC co-culture. AIN457 also significantly inhibited osteoclast cell differentiation. More importantly, in the SCIDhu model of human myeloma administration of AIN457 weekly for 4 weeks after the first detection of tumor in mice led to a significant inhibition of tumor growth and reduced bone damage compared with isotype control mice. To understand the mechanism of action of anti-IL-17A mAb, we report, here, that MM cells express IL-17A. We also observed that IL-17A knockdown inhibited MM cell growth and their ability to induce IL-6 production in co-cultures with BMSC. These pre-clinical observations suggest efficacy of AIN457 in myeloma and provide the rationale for its clinical evaluation for anti-myeloma effects and for improvement of bone disease.

Dedicator of cytokinesis 8 gene (DOCK8) deficiency is an immune disorder associated with autosomal recessive hyper-IgE syndrome, characterized by elevated IgE levels, atopic dermatitis, and predisposition to recurrent skin and lung infections.

The structural and dynamical features associated with the phase behavior of water confined in clay nanopores (2D confined water) are studied using positron annihilation spectroscopy, nuclear magnetic resonance, and dielectric relaxation spectroscopy techniques. We report the experimental evidence of a new phase transition (above the bulk freezing point of water) in nanoconfined water, in addition to a low-temperature transition in supercooled water. The study reveals it to be a structural rearrangement of water molecules associated with modification of hydrogen-bonded network. Evidence also suggests the dynamical arrest/immobilization of water layer near the clay platelet surface (bound water molecules) to be associated with this transition. This transition is a manifestation of the role of surface interaction on the phase behavior of confined liquids.

Sub-surface-initiated spalling, which is the classical mode of failure in rolling element bearings is significantly influenced by the inhomogeneous and stochastic nature of the material microstructure. This microstructural disorder is one of the primary reasons for scatter in fatigue lives for a seemingly identical batch of bearings. In this study, a stochastic fatigue model that takes the material microstructure explicitly into account is used to investigate dispersion in spalling lives for rolling element bearings. Material microstructures are generated stochastically using the process of Voronoi tessellation. Input parameters to the fatigue model are obtained from torsional fatigue tests. Spalling lives are found to follow a three-parameter Weibull distribution more closely compared with the conventionally used two-parameter Weibull distribution. The stress-life results generated using the model are found to correlate well with the Lundberg-Palmgren theory. Based on parametric studies, a new statistical life equation for bearing life is proposed which is similar in structure to the Lundberg-Palmgren equation with a modification term. Parameters in the life equation are functions of torsional fatigue parameters for the material.

Abstract: An analytical methodology has been developed for the separation of arsenic from ground water using inorganic material in neutral medium. The separation procedure involves the quantitative retention of arsenic on hydrated manganese dioxide, in neutral medium. The validity of the separation procedure has been checked by a standard addition method and radiotracer studies. Neutron activation analysis (NAA), a powerful measurement technique, has been used for the quantitative determination of arsenic.

Abstract: The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 µmol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p=0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p=0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (β2M)≥3.7 (p<0.0001), age ≥52.5 yr (p=0.002), performance status (PS) ≥2 (p=0.005) and patients with light-chain myeloma (p=0.03) had a significantly shorter OS, β2M≥3.7, PS≥2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome.

A simple and efficient method has been developed to preconcentrate natural protactinium from large quantity of monazite (5–10 g) and thorium concentrates (5–100 g), obtained from thorium plant stream on Dowex 1X8 in acid medium. Gamma-spectrometry, a powerful determination technique, has been used for quantitative determination of protactinium and uranium. Various parameters like sample preparation, optimization of the resin and sample size for 231Pa recovery, 231Pa/235U ratio have been studied in detail and are discussed.

Our previous studies have shown that activation of a related adhesion focal tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)-induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL-6), a known growth and survival factor for MM cells, blocks both RAFTK activation and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex-induced apoptosis is undefined. In this study, we demonstrate that protein-tyrosine phosphatase SHP2 mediates this protective effect. We show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells. SHP2 interacts with RAFTK through a region other than its Src homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM.

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30°C) but not at restrictive (37°C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30°C) but not at restrictive (37°C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.

The we of empirical antibiotic combinations in the treatmnt of febrile neutropenic patients has decreased complication-related mortality in cancer patients. We have analyzed retrospectively 499 consecutive episodes of fever in 432 patients with acute lymphoblastic leukemia over α 5-year period. We have compared various antibiotic combinations used empirically in our study. Of the febrile episodes, 92% were neutropenic. The most common site of clinical documentation was the lung. The most common pathogen isolated in our setting was Pseudomonas aeuroginosa (27.27%). The overall response rate to first-line empirical antibiotic combination was seen in 61.92%, the best results being with ceftazidime and amikacin combination (65.69%). A uniform antibiotic policy resulted in a decrease in mortality, with the number of deaths decreasing significantly in the 1989 to 1991 era (P = 0.00000003). The other contributing factors were an improvement in the supportive care with a reduction in length of hospital stay during induction. Our fungal isolates demonstrated 11 patients with documented fungal infection with a positive outcome in 8 patients.

Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.

Very early onset inflammatory bowel disease (VEOIBD) may correlate with multiple immunodeficiencies, including severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), chronic granulomatous disease (CGD), Wiskott-Aldrich syndrome (WAS), and IL-10 signaling defects. It may be difficult to differentiate between intestinal inflammation and immune dysfunction leading to systemic symptoms and elevated inflammatory markers. This patient, a 5-year-old male with very early onset Crohn's disease, chronic lung disease, 1p36 duplication, failure to thrive, eczema, and systemic infections including Candidemia, Klebsiella bacteremia, histoplasmosis, recurring pneumonia, multiple upper respiratory and sinus infections, and recurring IBD flares, presented due to concern for underlying primary immunodeficiency.

Periodic fever syndromes are a subset of autoinflammatory conditions that typically manifest in childhood. They often are diagnostic dilemmas due to their heterogeneous presentations. It is important for immunologists to be familiar with the unique features of these disorders. We present the case of a patient with suspected autoinflammatory disorder whose evaluation is ongoing due to recurrence of symptoms and negative testing.

Fevers are a common complaint among the pediatric population, and are frequently related to a viral or bacterial infection that resolves with conservative treatment or antibiotics. However, fevers of significance (greater than 38.4 degrees Celsius) occurring in a cyclicpattern with unusual associated symptoms are concerning for an underlying cause. Periodic fever syndromes are inherited disorders with recurrent fever and inflammation in the absence of infection or malignancy.

Following the publication of this article, the authors noted that the pomalidomide dose for the additional SC cohort in Fig. 1 was incorrectly listed. The correct dose for pomalidomide in the additional SC cohort should be the maximum tolerated dose of 4 mg/day, not 2 mg/day as listed in the original Fig. 1. The authors apologize for any inconvenience caused.

We have investigated two regimens for the mobilisation of stem cells prior to PBSC transplantation in MM. Regiman A: 125μg/m2GCSF b.d. for 7 days with harvest of stem cells days 5–8. Regimen B: 12–16μg/kg for 4 days with harvest days 4 and 5. For each regimen the median total cell count, CFU-GM and CD34 + counts and days to engraftment as measured by time to attainment of neutrophil count 500 were calculated and compared by the Mann-Whitney non-parametric test.

Between November 1992 and November 1994, 73 myeloma patients were treated with high dose Melphalan (200mg/m2) followed by rescue with peripheral blood stem cells. All patients had received induction treatment with C-VAMP until maximum response. 24 patients were newly diagnosed while 49 patients had received some form of previous treatment. Response and engraftment details are shown in the table below.New Pts (24)Previous treatment(49) PvalueResponseCR13 (55%)11 (23%)0.007PR9 (37%)20 (40%)NSNR2 (8%)15 (31%)0.03Died0 (0%)3 (6%)EngraftmentPits 25×109/l14 days17 days0.004Neuts 1000/L24 days34 days0.002Inf start (Med)55 days68 days0.017The overall survival by the Kaplan Meier estimate at 2 years is 79.3% with a median follow up of 7.75 months and the progression free survival is 58% in the whole group of 73 patients. Interferon (inf) maintenance was started at a median of 61 days in 58/73 patients. We therefore conclude that the previously untreated group is a better risk group with respect to achieving remission as well as rapid engraftment. Inf was also started earlier in the untreated group. Longer follow up will be required however to comment on the efficacy of PBSCT. A CR rate of 55% in previously untreated patients is lower than our previously reported CR rate with ABMT in a comparable group of patients and the possibility of contamination of the stem cell grafts with myeloma should be borne in mind.

204 previously untreated Multiple Myeloma patients received a four day infusional chemotherapy schedule with Vincristine, Adriamycin, Methyl prednisolone with the addition of Cyclophosphamide and/or Verapamil as outpatient treatment as part of their induction therapy in the study period between April 1985 and March 1994. The aim of this treatment was to reduce tumor burden and marrow infiltration prior to high dose therapy. The objective of this analysis was to ascertain response to cytoreductive treatment prior to autografting and to see if addition of Cyclophosphamide and/or Verapamil influenced response. Among the 204 patients, 91 received C-VAMP chemotherapy, 75 received VAMP and 38 patients received Verapamil in addition to C-VAMP The median number of courses to achieve maximum response in the whole group was 5 (range 1–11). The overall response to induction treatment was 71.0% (144/204) with 18.0% (37/204) achieving a complete response (CR). The response in the three subsets of patients is shown in the following table.Induction treatmentNo. patientsCR (%)PvalueVAMP756 (7.9%)C-VAMP9122 (24%)0.04V-C-VAMP389 (23%)Seventeen patients have died during induction with 4.0% (9/204) deaths as a result of induction treatment. We therefore conclude that a median of 5 courses of cytoreductive treatment is required for maximum response. The CR rate with just cytoreductive treatment is low and requires consolidation with high dose treatment and autografting. The addition of Cyclophosphamide to VAMP alone produces significantly better responses. The addition of Verapamil to the C-VAMP has not made any difference to outcome.

Autografting became part of our myeloma treatment strategy in September 1986. Since then until March 1994, 195 new untreated patients between the ages of 30 and 70 years received induction chemotherapy with either VAMP, C-VAMP or V-C-VAMP. The complete remission (CR) rate following induction was 18%. 144 (74%) of these patients went on to receive high dose (HD) treatment (Busulfan or Melphalan), of which 110 (56%) received high dose melphalan plus an autograft. Analysis is as of December 1994 with a median follow up of 41 months. Among the 110 patients, 89 received bone marrow while 21 patients were rescued with peripheral blood stem cells. The complete remission rate after HD in this group of patients was 74.5%. 21% achieved a partial remission and there were only 3 non-responders. There was 1 (0.9%) transplanted related death and therefore response could not be evaluated.The actuarial overall survival of the above transplanted patients by the Kaplan Meier estimate was 52.7% at 6 years and 50% of the patients remained progression free at 29 months. Fifty-seven patients have progressed to date and 33 have died. All but one death are due to disease progression. Sixty-eight patients subsequently went on to maintenance Interferon. Analysis of the total series of 195 patients shows a complete remission rate of 54% (104/195) with 35% of the complete responders surviving at seven years. We thus conclude that cytoreductive treatment followed by high dose chemotherapy produces high remission rates which in turn results in improved survival. Interferon has been shown to be effective in maintaining remission and has been incorporated as maintenance treatment. This should therefore be first line treatment in young myeloma patients.

Follow up data of 204 Myeloma patients seen at the Royal Marsden were analysed for factors predicting the overall survival. All these patients were newly diagnosed and went on to receive VAMP/C-VAMP/V-C-VAMP, infusional cytoreductive treatment. 146 of these patients received some form of high dose treatment (Melphalan or Busulfan). A Cox regression analysis was carried out on clinical and laboratory factors just prior to treatment. Multivariate analysis revealed stage (P=0.0001), Hb (P=0.03), serum Calcium (P=0.01) and performance status (P=0.01) as independent prognostic factors. Beta2 microglobulin was however not included in this analysis as this was not done routinely in the initial patients (n=51). When however we repeated the analysis after the elimination of these 51 patients, Beta2 microglobulin was the single most important prognostic variable (P<0.0001). We then looked at the same prognostic variables in the 146 patients who received high dose treatment and found only Hb (P=0.03) and serum Calcium (P=0.02) emerging as independent prognostic variables. On repeating the analysis on those who had Beta2 microglobulin estimation, this was again the only variable which was independently significant (P=0.001). This therefore illustrates the point that the prognostic value of different variables may be influenced by successful treatment. We conclude from the above data that pretreatment Beta2 microglobulin, serum calcium and haemoglobin affect the overall survival in myeloma patients in spite of aggressive treatment.

The sunflower midge, Contarinia schulzi Gagné, causes economic damage by inducing abnormal growth in infested heads (capitula) of sunflower, Helianthus annuus L. The primary objective of this study was to determine whether sunflower midge damage could be simulated and whether that simulated damage could be used to select midgetolerant sunflower germplasm. An additional objective was to develop a quantitative alternative to the scoring systems used to visually estimate damage. Sunflower plants were treated by injecting buds with the synthetic auxin 2,4-dichlorophenoxy acetic acid (2,4-D), which resulted in a distortion of the head morphology that was similar in appearance to the damage caused by the sunflower midge. The extent of distortion depended not only on the dose of 2,4-D but also on the size and growth stage of the head when injected. Among sunflower hybrids tested, resistance to the sunflower midge was significantly, negatively correlated with 2,4-D damage. Therefore, injection of sunflower heads with 2,4-D appears to be an effective method of screening sunflower germplasm for tolerance to the sunflower midge. Two distortion indices, based on measurements of head shape, were compared with the visual damage system. Although the visual rating system is faster, distortion index 2 gave similar results and is preferred when it is necessary to avoid individual differences in scoring techniques.