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Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol consumption that induce a "precancerous field," with phosphoinositide 3-kinase (PI3K) signaling being a common driver. However, the preclinical effectiveness of PI3K inhibitors has not necessarily translated to remarkable benefit in HNSCC patients. Thus, we sought to determine how precancerous keratinocytes influence HNSCC proliferation, cancer stem cell (CSC) maintenance, and response to PI3K inhibitors. We used the NOK keratinocyte cell line as a model of preneoplastic keratinocytes because it harbors two frequent genetic events in HNSCC, CDKN2A promoter methylation and TP53 mutation, but does not form tumors. NOK cell coculture or NOK cell-conditioned media promoted HNSCC proliferation, PI3K inhibitor resistance, and CSC phenotypes. SOMAscan-targeted proteomics determined the relative levels of1300 analytes in the media conditioned by NOK cells and HNSCC cells ± PI3K inhibitor. These results demonstrated that NOK cells release abundant levels of ligands that activate epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR), two receptor tyrosine kinases with oncogenic activity. Inhibition of EGFR, but not FGFR, blunted PI3K inhibitor resistance and CSC phenotypes induced by NOK cells. Our results demonstrate that precancerous keratinocytes can directly support neighboring HNSCC by activating EGFR. Importantly, PI3K inhibitor sensitivity was not necessarily a cancer cell-intrinsic property, and the tumor microenvironment impacts therapeutic response and supports CSCs. Additionally, combined inhibition of EGFR with PI3K inhibitor diminished EGFR activation induced by PI3K inhibitor and potently inhibited cancer cell proliferation and CSC maintenance.

Purpose To investigate the impact of rectal spacing on inter‐fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing SBRT with a 0.35 T MRI‐Linac. Materials and Methods We evaluated and compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI‐Linac. Each group consisted of 10 randomly selected patients that received prostate SBRT to a total dose of 36.25 Gy in five fractions. Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified. We also assessed whether adaptive planning was needed to meet constraints for each fraction. Results On average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p

Purpose To develop a deep learning model to generate synthetic CT for MR‐only radiotherapy of prostate cancer patients treated with 0.35 T MRI linear accelerator. Materials and Methods A U‐NET convolutional neural network was developed to translate 0.35 T TRUFI MRI into electron density map using a novel cost function equalizing the contribution of various tissue types including fat, muscle, bone, and background air in training. The impact of training time, dataset size, image standardization, and data augmentation approaches was also quantified. Mean absolute error (MAE) between synthetic and planning CTs was calculated to measure the goodness of the model. Results With 20 patients in training, our U‐NET model has the potential to generate synthetic CT with a MAE of about 29.68 ± 4.41, 16.34 ± 2.67, 23.36 ± 2.85, and 105.90 ± 22.80 HU over the entire body, fat, muscle, and bone tissues, respectively. As expected, we found that the number of patients used for training and MAE are nonlinearly correlated. Data augmentation and our proposed loss function were effective to improve MAE by ~9% and ~18% in bony voxels, respectively. Increasing the training time and image standardization did not improve the accuracy of the model. Conclusion A U‐NET model has been developed and tested numerically to generate synthetic CT from 0.35T TRUFI MRI for MR‐only radiotherapy of prostate cancer patients. Dosimetric evaluation using a large and independent dataset warrants the validity of the proposed model and the actual number of patients needed for the safe usage of the model in routine clinical workflow.

Renal cell carcinoma (RCC) is not a single disease but is made up of several different histologically defined subtypes that are associated with distinct genetic alterations which require subtype specific management and treatment. Papillary renal cell carcinoma (pRCC) is the second most common subtype after conventional/clear cell RCC (ccRCC), representing ~20% of cases, and is subcategorized into type 1 and type 2 pRCC. It is important for preclinical studies to have cell lines that accurately represent each specific RCC subtype. This study characterizes seven cell lines derived from both primary and metastatic sites of type 1 pRCC, including the first cell line derived from a hereditary papillary renal carcinoma (HPRC)‐associated tumor. Complete or partial gain of chromosome 7 was observed in all cell lines and other common gains of chromosomes 16, 17, or 20 were seen in several cell lines. Activating mutations of MET were present in three cell lines that all demonstrated increased MET phosphorylation in response to HGF and abrogation of MET phosphorylation in response to MET inhibitors. CDKN2A loss due to mutation or gene deletion, associated with poor outcomes in type 1 pRCC patients, was observed in all cell line models. Six cell lines formed tumor xenografts in athymic nude mice and thus provide in vivo models of type 1 pRCC. These type 1 pRCC cell lines provide a comprehensive representation of the genetic alterations associated with pRCC that will give insight into the biology of this disease and be ideal preclinical models for therapeutic studies.

Citizen science has become a popular way to collect biodiversity data and engage the wider public in scientific research. It has the potential to improve the knowledge and skills of participants, and positively change their behaviour and attitude towards the environment. Citizen science outcomes are particularly valuable for wildlife conservation, as they could help alleviate human impacts on the environment. We used an online questionnaire to investigate the consequences of participating in an Australian turtle mapping app, TurtleSAT, on skills and knowledge gain, and test for any association between these gains and behavioural or attitudinal changes reported by the participants. One hundred and forty‐eight citizen scientists completed our questionnaire, mostly from the states of New South Wales and Victoria. TurtleSAT was the third most common source of correct answers about turtle ecology and conservation, after a talk about turtles and personal observations/research. Citizen scientists who participated more often were more knowledgeable about turtles than infrequent users. Self‐reported gains in knowledge and skills were positively linked to attitudinal and behavioural changes, such as being more aware of turtles on roads. However, behaviour and attitude changes were not related to participation rate. Respondents also reported that after learning about the current decline in turtle populations, they adopted several turtle‐friendly practices, such as habitat restoration or moving turtles out of harm's way, underlining the importance of increasing people's awareness on species declines. The reported changes in attitudes and behaviours are likely to positively impact the conservation of Australian freshwater turtles. Engagement with citizen science projects like TurtleSAT may result in participants being more interested in the natural world, by learning more about it and being more exposed to it, and therefore contributing more actively to its protection. A free Plain Language Summary can be found within the Supporting Information of this article.

Insufficient funding is a major impediment to conservation efforts around the world. In the United States, a decline in hunting participation threatens sustainability of the “user‐pay, public benefit” model that has supported wildlife conservation for nearly 100 years, forcing wildlife management agencies to contemplate alternative funding strategies. We investigated support for potential funding options among diverse college students, a rapidly expanding and politically active voting bloc with a potentially powerful influence on the future of conservation. From 2018 to 2020, we surveyed 17,203 undergraduate students at public universities across 22 states. Students preferred innovative approaches to conservation funding, with 72% supporting funding derived from industry sources (e.g., natural resource extraction companies), 63% supporting state sources (e.g., general sales tax), and 43% supporting conventional user‐based sources such as license fees and excise taxes associated with outdoor recreation activities (e.g., hunting). Findings emphasize the need to broaden the base of support for conservation funding and highlight the importance of considering the preferences and perspectives of young adults and other diverse beneficiaries of wildlife conservation.

Summary CRISPR/Cas9 and Cas12a (Cpf1) nucleases are two of the most powerful genome editing tools in plants. In this work, we compared their activities by targeting maize glossy2 gene coding region that has overlapping sequences recognized by both nucleases. We introduced constructs carrying SpCas9‐guide RNA (gRNA) and LbCas12a‐CRISPR RNA (crRNA) into maize inbred B104 embryos using Agrobacterium‐mediated transformation. On‐target mutation analysis showed that 90%–100% of the Cas9‐edited T0 plants carried indel mutations and 63%–77% of them were homozygous or biallelic mutants. In contrast, 0%–60% of Cas12a‐edited T0 plants had on‐target mutations. We then conducted CIRCLE‐seq analysis to identify genome‐wide potential off‐target sites for Cas9. A total of 18 and 67 potential off‐targets were identified for the two gRNAs, respectively, with an average of five mismatches compared to the target sites. Sequencing analysis of a selected subset of the off‐target sites revealed no detectable level of mutations in the T1 plants, which constitutively express Cas9 nuclease and gRNAs. In conclusion, our results suggest that the CRISPR/Cas9 system used in this study is highly efficient and specific for genome editing in maize, while CRISPR/Cas12a needs further optimization for improved editing efficiency.

The clinical course of breast cancer varies from one patient to another. Currently, the choice of therapy relies on clinical parameters and histological and molecular tumor features. Alas, these markers are informative in only a subset of patients. Therefore, additional predictors of disease outcome would be valuable for treatment stratification. Extensive studies showed that the degree of variation of the nuclear DNA content, i.e., aneuploidy, determines prognosis. Our aim was to further elucidate the molecular basis of aneuploidy. We analyzed five diploid and six aneuploid tumors with more than 20 years of follow-up. By performing FISH with a multiplexed panel of 10 probes to enumerate copy numbers in individual cells, and by sequencing 563 cancer-related genes, we analyzed how aneuploidy is linked to intratumor heterogeneity. In our cohort, none of the patients with diploid tumors died of breast cancer during follow-up in contrast to four of six patients with aneuploid tumors (mean survival 86.4 months). The FISH analysis showed markedly increased genomic instability and intratumor heterogeneity in aneuploid tumors. MYC gain was observed in only 20% of the diploid cancers, while all aneuploid cases showed a gain. The mutation burden was similar in diploid and aneuploid tumors, however, TP53 mutations were not observed in diploid tumors, but in all aneuploid tumors in our collective. We conclude that quantitative measurements of intratumor heterogeneity by multiplex FISH, detection of MYC amplification and TP53 mutation could augment prognostication in breast cancer patients.

Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.

Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead-based microarray covering 1,500 CpG sites in over 800 genes. Methylation levels in individual CpG sites were compared using a t-test, and results were summarized by computing p-values. A total of 12 candidate genes (ADCYAP1, ASCL1, ATP10, CADM1, DCC, DBC1, HS3ST2, MOS, MYOD1, SOX1, SOX17 and TMEFF2) identified by DNA methylation profiling, plus an additional three genes identified from the literature (EPB41L3, MAL and miR-124) were chosen for validation in an independent set of 167 liquid-based cytology specimens using pyrosequencing and targeted, next-generation bisulfite sequencing. Of the 15 candidate gene markers, 10 had an area under the curve (AUC) of ≥ 0.75 for discrimination of high grade squamous intraepithelial lesions or worse (HSIL+) from

Advice seeking is often the most critical success factor in today's IT project teams. To understand how advice seekers are motivated, we integrate the antecedents of advice seeking—as defined by network theory (Granovetter, 1983)—into a cost/benefit model based on expectancy theory (Vroom, 1964). To contribute to the research on advice network formation, we integrate the role of task uncertainty—one of the defining characteristics of IT projects—into that research (Wallace & Keil, 2004). Based on a controlled quasi-experiment, this study demonstrates that when task uncertainty is low, individuals with attractive personalities and similar demographics will be sought out for advice more frequently, regardless of their knowledge and resources (i.e., the benefits to the advice seekers). However, when task uncertainty is high, individuals with greater knowledge and access to resources are sought out more often in an advice network. These results provide clarity to prior research that has found mixed results concerning the effectiveness of the traditional antecedents to advice seeking (e.g., knowledge, power, and transactive memory) (e.g., Xu, Kim, & Kankanhalli, 2010a). In addition, project managers may choose to alter their team structure in order to optimize the advice network based on the anticipated level of IT project risk or task uncertainty.

This article explores the tumultuous path to publication that begins for many of us with trying to publish our dissertation. We invited Roy J. Lewicki and J. Keith Murnighan—the 2013 and 2015 recipients of the International Association for Conflict Management (IACM) Lifetime Achievement Award—to reflect on this process, as neither of them were successful in getting their dissertation articles published. We also asked them to reflect on the twists and turns of academic publishing, and we asked Max Bazerman to integrate these reflections. Together, we hope to spark generative conversations that will enable scholars to successfully navigate their academic careers.

Background The classic histopathologic features of lichen sclerosus et atrophicus (LS) include lymphoplasmacytic inflammation below a zone of dermal edema and sclerosis. The presence of eosinophils in LS has received little attention, but the finding of tissue eosinophils, particularly eosinophilic spongiosis in LS, has been suggested as a marker for the coexistence of autoimmune bullous disease or allergic contact dermatitis (or both). We sought to determine whether the histopathologic presence of dermal eosinophils or eosinophilic spongiosis (or both) in biopsies from patients with LS is associated with autoimmune bullous disease, autoimmune connective tissue disease or allergic contact dermatitis. Methods A retrospective review of the histopathology and medical records of 235 patients with LS who were evaluated from June 1992 to June 2012 was performed. Results Sixty-nine patients (29%) had eosinophils on histopathology. Among patients with associated diseases, a statistically significant association between the eosinophil cohort and the cohort without eosinophils was not detected. Conclusions The importance of eosinophils is uncertain, but our data suggest that the finding of tissue eosinophils alone is not sufficient to prompt an extensive workup for additional diagnoses.

Smartphones are increasingly penetrating business and consumer markets, and mobile applications apps have engendered a large and innovative market. Whereas apps are useful, they also present new forms of privacy risk associated with users' personal and location data. However, these dangers do not appear to increase the perceived risk or reduce the trust consumers demonstrate when using apps. Many information technology IT trust indicators are well documented such as the quality of the IT, trust assurances, brand recognition and social influences. However, these traditional indicators appear to have a lesser impact on the adoption of mobile commerce via apps because of the nature of mobile-app adoption and subsequent information disclosure. As a result, we draw from social cognitive theory and its construct of self-efficacy in particular to explain perceived mobile-app risk and provider trust. Through two controlled experiments, we demonstrate the strong direct effect of mobile-computing self-efficacy on users' initial trust in location-based app vendors as well as their perceived risk of disclosing information - regardless of the actual trustworthiness of the app vendor. The results imply that being skilled in the latest smartphones and apps can cause users to place greater trust in app providers and perceive less risk in the app itself, even when the intentions of the app providers cannot be verified.

It is time for reading in Ms. Wilson ’ s (pseudonym) fourth- and fifth- grade class. She names the students who will meet with her and asks that they bring their daybooks. The students who meet with Ms. Wilson retrieve composition books with black and white marbled covers, and they enthusiastically settle into their chairs in the back of the room with the teacher. Purposeful chatter fills the room. Students in the various literacy centers have the same composition books open, busily writing and reading. Karin (first author) witnessed a similar scene every time she visited Ms. Wilson ’ s classroom. In this article, we explain what a daybook is, how to organize daybooks, what one teacher included in her daybooks, and how these daybooks helped students to comprehend and discuss texts.

The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1,500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p values of ≤ 10(-7) between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33-8.91) for ASCL2 to 18.61 (95%-CI: 5.50-62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy.

In this article, we report the synthesis of a new bimodal surface ligand morphology on silica nanoparticles. Combining grafting-to and grafting-from approaches, in this study, we demonstrated the efficacy of anthracene surface modification for improving the dielectric breakdown strength (DBS) under alternating-current and direct-current conditions and that of a matrix-compatible polymer brush for controlling the nanofiller (NF) dispersion. Ligand-modified spherical colloidal SiO2 nanoparticles (∼14 nm in diameter) were mixed into polypropylene, and the resulting dispersion was improved over the unmodified particles, as shown with transmission electron microscopy. The results suggest that the electronic structure of the anthracene-modified particle surface was critical to the improvement in DBS. In addition, the DBS of the composite was shown to depend on the dispersion state of the filler and the mode of stress; this indicated that the individually dispersed nanoparticles were not necessarily the optimal morphology for all stress conditions. Additionally, the precise nature of the matrix-compatible brush was less important than the NF dispersion it produced. The bimodal grafted architectural design has provided a promising solution for the control of the dispersion and surface properties, especially for high-molecular-weight polymer matrices. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44347.

Rationale Electrospray ionisation mass spectrometry (ESI-MS) is a useful tool for exploring the speciation of solution-phase metal complexes; however, the quantification of ternary systems is challenging due to the differences in the electrospray response of different species. Here, the Th-Mn-EDTA system was investigated to evaluate the capability of ESI-MS for quantifying the species present. Methods Increasingly complex mixtures of Th(IV), Mn(II) and EDTA were analysed using manual flow injection of samples into an HPLC grade water mobile phase delivered to an ion trap mass spectrometer fitted with an ESI interface (ThermoQuest Finnigan Mat LCQ). Mass spectra were obtained in the positive and negative ion modes over a mass-to-charge (m/z) range from 50-2000. Results The instrumental response to EDTA was affected by the addition of Th(NO(3))(4) but not MnCl(2), while the response to both Th-EDTA and Mn-EDTA species was affected by addition of the other metal salt. Internal standards were also found to suppress signals to different extents. Therefore, each signal suppression was carefully quantified as the solution became more complex, and signal correction factors were used in conjunction with regular external calibration. Mixed metal signals were quantified adequately. Conclusions This study showed the complexity of quantifying a ternary system involving different co-existing species. Nonetheless, the step-wise protocol developed provided quantitative data on the displacement of Mn from its EDTA complex by Th.

Aim: Exercise and insulin each increase microvascular blood flow and enhance glucose disposal in skeletal muscle. We have reported that insulin-mediated microvascular recruitment in a diet-induced model of insulin resistance (high-fat feeding for 4 weeks) is markedly impaired; however, the effect of muscle contraction in this model has not been previously explored. Methods: We fed rats either normal (ND, 10% calories from fat) or high-fat (HFD, 60% calories from fat) diets ad libitum for 4–8 weeks. Animals were then anaesthetized and one hindlimb electrically stimulated to contract at 0.05, 0.1 and 2 Hz (field stimulation, 30 V, 0.1 ms duration) in 15 min stepwise increments. Femoral artery blood flow (Transonic flow probe), muscle microvascular blood flow (hindleg metabolism of 1-methylxanthine and contrast-enhanced ultrasound) and muscle glucose disposal (uptake of radiolabelled 2-deoxy- d -glucose and hindleg glucose disappearance) were measured. Results: Both ND and HFD rats received the same voltage across the leg and consequently developed the same muscle tension. Femoral artery blood flow in the contracting leg increased during 2 Hz contraction, but not during the lower frequencies and these effects were similar between ND and HFD rats. Muscle microvascular blood flow significantly increased in a contraction frequency-dependent manner, and preceded increases in total limb blood flow and these effects were similar between ND and HFD rats. Muscle glucose disposal was markedly elevated during 2 Hz contraction and was comparable between ND and HFD rats. Conclusion: Contraction-mediated muscle microvascular recruitment and glucose uptake are not impaired in the HFD insulin resistant rat.

BACKGROUND: Microorganisms mediate biochemical transformations of phosphorus (P) in soil. This is of particular importance in highly weathered soils, which are usually P deficient. This study aimed to extend understanding of the separate role of bacteria and fungi in P transformations in aggregates of a highly weathered soil, by adding P-stripped rice straw and microorganism inhibitors to aggregates. RESULTS: The amount of microbial biomass phosphorus (MB-P) in the treatment with rice straw alone increased by over two-fold during 16 days. At the end of 28 d, the amount of inorganic-P in Fe-, Al-, and Ca-bound fractions decreased, whilst the amount of organic-P increased substantially (P < 0.01). The effect of bacterial inhibitors (tetracycline and streptomycin sulphate) on P immobilisation was very small in the early phase (0–4 d), but became pronounced after 8 days, whilst the fungal inhibitor (actidione) initially caused a decrease in P immobilisation by about 60%, but had no effect after that. CONCLUSION: Fungi and bacteria immobilise P in soil aggregates, with fungi being responsible initially. However, bacteria become dominant subsequently and immobilise P from the inorganic fractions. Copyright © 2011 Society of Chemical Industry

Management and businesses in general are constantly facing important ethical challenges. In the current special issue, we identify the widespread emergence of unethical decision-making and behaviour in management as an important topic for a future research agenda. Specifically, we promote the use of a behavioural business ethics approach to better understand when management, leaders and businesses are inclined to act unethically and why this is the case. A behavioural business ethics approach which relies on important insights from psychology should be a necessary addition and complementary to the traditional normative approaches used in business ethics.

The southwestern edge of the natural range of smallmouth bass Micropterus dolomieu contains streams that become disconnected pools during summer primarily owing to hydrogeologic conditions, including high evapotranspiration rates. These conditions may complicate fisheries management by affecting fish behavior or mortality rates. The objectives of this study were to characterize summer habitat use by smallmouth bass, estimate the changes in the extent of available habitat, describe summer movement patterns, and estimate summer survival rates. Radio transmitters were implanted into 60 smallmouth bass during May 2006, and the fish were tracked until October in the forks of the Illinois Bayou, which drains a portion of the Ozark National Forest. Habitat characteristics were measured as the summer progressed, and during this time most riffle–run habitat dried completely, resulting in a series of disconnected pools. The decreases in wetted area exceeded 55% in certain 2-km study reaches; however, small...

This article outlines the context in geography and statistics in the mid 1960s, at the height of geography's so-called “quantitative revolution,” that led us into a long-term collaboration about spatial statistics, which has continued in surges and lulls for some 40 years. We focus upon problems in spatial autocorrelation, including the measurement of autocorrelation, distribution theory, and variable geographical lattices. This narrative may not describe how it was, but it does describe how we remember the events of the time. Que estabamos pensando? El presente articulo intenta esbozar el contexto academico e intelectual en las disciplinas de Geografia y Estadistica a mediados de la decada de los 60, durante el auge de lo que se conoce como la revolucion cuantitativa en Geografia. En este periodo se inicio una prolongada colaboracion entre ambas disciplinas que tiene como eje el estudio de la estadistica espacial y que ha continuado con altos y bajos por alrededor de 40 anos. Nos concentramos en problemas alrededor del concepto de autocorrelacion espacial, tales como la medicion de la autorrelacion, teorias de distribucion, y diferentes latices o configuraciones geograficas. La narracion que presentamos no necesariamente describe los eventos ‘como fueron’ sino mas bien los eventos ‘como los recordamos’ nosotros. 计量地理学的思考 本文概述了20世纪60年代中期地理学与统计学之间的联姻，这一时期也是所谓地理学 “计量革命”的巅峰时刻。它引导我们进入了空间统计学的一个长期协作阶段，并在跌宕起伏中持续了约四十年。我们着重讨论了空间自相关中的空间自相关测度、分布理论以及可变地理格网问题。或许本文未能对上述问题进行充分的阐述，但它能唤醒我们对这段时间里所发生事件的回忆。

Chromosome abnormalities, identified using a banding technique and additional to the Ph, are reported in 10 consecutive cases of transformed chronic granulocytic leukaemia. In most of the cases the abnormalities were non random. In 2 cases serial studies were performed and additional abnormalities found, antedating transformation by one week and two months respectively. In 2 others the Ph status had been established during the chronic phase of the disease. In the remaining cases the first chromosome analysis was performed at the time of transformation.